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Organellar DNA (oDNA) is DNA contained in organelles (such as mitochondria and chloroplasts), outside the nucleus of eukaryotic cells.
Mitochondria contain mitochondrial DNA
Plastids (e.g., chloroplasts) contain plastid DNA
== Inheritance of organelle DNA ==
The traits encoded by this type of DNA, in animals, generally pass from mother to offspring rather than from the father in a process called cytoplasmic inheritance. This is due to the ovum provided from the mother being larger than the male sperm cell, and therefore has more organelles, where the organellar DNA is found.
Although maternal inheritance is most common, there are also paternal and biparental patterns of inheritance that take place. The latter two patterns of inheritance are found most often in plants.
Recombination of organelle DNA is very limited, meaning that any traits that are encoded by the oDNA are likely to remain the same as they are passed from generation to generation.
== Structure ==
Unlike nuclear DNA, which is present as linear molecules inside the chromosomes, the entire genomes of chloroplasts and mitochondria are present on a single molecule of double-stranded circular DNA molecule; this is very similar structure to a bacterial chromosome.
Although the functionality and genetic structure vary significantly between different organelles and their host species, genetic characteristic patterns allow the differentiation between nucleolar and organellar DNA. A recently published machine-learning approach using only the genome sequences and multiple genome annotation tools can classify them.
== See also ==
Nuclear DNA
Non-Mendelian Inheritance
== References == | Wikipedia/Organellar_DNA |
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome.
Recombinant DNA is the general name for a piece of DNA that has been created by combining two or more fragments from different sources. Recombinant DNA is possible because DNA molecules from all organisms share the same chemical structure, differing only in the nucleotide sequence. Recombinant DNA molecules are sometimes called chimeric DNA because they can be made of material from two different species like the mythical chimera. rDNA technology uses palindromic sequences and leads to the production of sticky and blunt ends.
The DNA sequences used in the construction of recombinant DNA molecules can originate from any species. For example, plant DNA can be joined to bacterial DNA, or human DNA can be joined with fungal DNA. In addition, DNA sequences that do not occur anywhere in nature can be created by the chemical synthesis of DNA and incorporated into recombinant DNA molecules. Using recombinant DNA technology and synthetic DNA, any DNA sequence can be created and introduced into living organisms.
Proteins that can result from the expression of recombinant DNA within living cells are termed recombinant proteins. When recombinant DNA encoding a protein is introduced into a host organism, the recombinant protein is not necessarily produced. Expression of foreign proteins requires the use of specialized expression vectors and often necessitates significant restructuring by
foreign coding sequences.
Recombinant DNA differs from genetic recombination in that the former results from artificial methods while the latter is a normal biological process that results in the remixing of existing DNA sequences in essentially all organisms.
== Production ==
Molecular cloning is the laboratory process used to produce recombinant DNA. It is one of two most widely used methods, along with polymerase chain reaction (PCR), used to direct the replication of any specific DNA sequence chosen by the experimentalist. There are two fundamental differences between the methods. One is that molecular cloning involves replication of the DNA within a living cell, while PCR replicates DNA in the test tube, free of living cells. The other difference is that cloning involves cutting and pasting DNA sequences, while PCR amplifies by copying an existing sequence.
Formation of recombinant DNA requires a cloning vector, a DNA molecule that replicates within a living cell. Vectors are generally derived from plasmids or viruses, and represent relatively small segments of DNA that contain necessary genetic signals for replication, as well as additional elements for convenience in inserting foreign DNA, identifying cells that contain recombinant DNA, and, where appropriate, expressing the foreign DNA. The choice of vector for molecular cloning depends on the choice of host organism, the size of the DNA to be cloned, and whether and how the foreign DNA is to be expressed. The DNA segments can be combined by using a variety of methods, such as restriction enzyme/ligase cloning or Gibson assembly.
In standard cloning protocols, the cloning of any DNA fragment essentially involves seven steps: (1) Choice of host organism and cloning vector, (2) Preparation of vector DNA, (3) Preparation of DNA to be cloned, (4) Creation of recombinant DNA, (5) Introduction of recombinant DNA into the host organism, (6) Selection of organisms containing recombinant DNA, and (7) Screening for clones with desired DNA inserts and biological properties.
These steps are described in some detail in a related article (molecular cloning).
== DNA expression ==
DNA expression requires the transfection of suitable host cells. Typically, either bacterial, yeast, insect, or mammalian cells (such as Human Embryonic Kidney cells or CHO cells) are used as host cells.
Following transplantation into the host organism, the foreign DNA contained within the recombinant DNA construct may or may not be expressed. That is, the DNA may simply be replicated without expression, or it may be transcribed and translated and a recombinant protein is produced. Generally speaking, expression of a foreign gene requires restructuring the gene to include sequences that are required for producing an mRNA molecule that can be used by the host's translational apparatus (e.g. promoter, translational initiation signal, and transcriptional terminator). Specific changes to the host organism may be made to improve expression of the ectopic gene. In addition, changes may be needed to the coding sequences as well, to optimize translation, make the protein soluble, direct the recombinant protein to the proper cellular or extracellular location, and stabilize the protein from degradation.
== Properties of organisms containing recombinant DNA ==
In most cases, organisms containing recombinant DNA have apparently normal phenotypes. That is, their appearance, behavior and metabolism are usually unchanged, and the only way to demonstrate the presence of recombinant sequences is to examine the DNA itself, typically using a polymerase chain reaction (PCR) test. Significant exceptions exist, and are discussed below.
If the rDNA sequences encode a gene that is expressed, then the presence of RNA and/or protein products of the recombinant gene can be detected, typically using RT-PCR or western hybridization methods. Gross phenotypic changes are not the norm, unless the recombinant gene has been chosen and modified so as to generate biological activity in the host organism. Additional phenotypes that are encountered include toxicity to the host organism induced by the recombinant gene product, especially if it is over-expressed or expressed within inappropriate cells or tissues.
In some cases, recombinant DNA can have deleterious effects even if it is not expressed. One mechanism by which this happens is insertional inactivation, in which the rDNA becomes inserted into a host cell's gene. In some cases, researchers use this phenomenon to "knock out" genes to determine their biological function and importance. Another mechanism by which rDNA insertion into chromosomal DNA can affect gene expression is by inappropriate activation of previously unexpressed host cell genes. This can happen, for example, when a recombinant DNA fragment containing an active promoter becomes located next to a previously silent host cell gene, or when a host cell gene that functions to restrain gene expression undergoes insertional inactivation by recombinant DNA.
== Applications of recombinant DNA ==
Recombinant DNA is widely used in biotechnology, medicine and research. Today, recombinant proteins and other products that result from the use of DNA technology are found in essentially every pharmacy, physician or veterinarian office, medical testing laboratory, and biological research laboratory. In addition, organisms that have been manipulated using recombinant DNA technology, as well as products derived from those organisms, have found their way into many farms, supermarkets, home medicine cabinets, and even pet shops, such as those that sell GloFish and other genetically modified animals.
The most common application of recombinant DNA is in basic research, in which the technology is important to most current work in the biological and biomedical sciences. Recombinant DNA is used to identify, map and sequence genes, and to determine their function. rDNA probes are employed in analyzing gene expression within individual cells, and throughout the tissues of whole organisms. Recombinant proteins are widely used as reagents in laboratory experiments and to generate antibody probes for examining protein synthesis within cells and organisms.
Many additional practical applications of recombinant DNA are found in industry, food production, human and veterinary medicine, agriculture, and bioengineering. Some specific examples are identified below.
=== Recombinant chymosin ===
Found in rennet, chymosin is the enzyme responsible for hydrolysis of κ-casein to produce para-κ-casein and glycomacropeptide, which is the first step in formation of cheese, and subsequently curd, and whey. It was the first genetically engineered food additive used commercially. Traditionally, processors obtained chymosin from rennet, a preparation derived from the fourth stomach of milk-fed calves. Scientists engineered a non-pathogenic strain (K-12) of E. coli bacteria for large-scale laboratory production of the enzyme. This microbiologically produced recombinant enzyme, identical structurally to the calf derived enzyme, costs less and is produced in abundant quantities. Today about 60% of U.S. hard cheese is made with genetically engineered chymosin. In 1990, FDA granted chymosin "generally recognized as safe" (GRAS) status based on data showing that the enzyme was safe.
=== Recombinant human insulin ===
Recombinant human insulin has almost completely replaced insulin obtained from animal sources (e.g. pigs and cattle) for the treatment of type 1 diabetes. A variety of different recombinant insulin preparations are in widespread use. Recombinant insulin is synthesized by inserting the human insulin gene into E. coli, or yeast (Saccharomyces cerevisiae) which then produces insulin for human use. Insulin produced by E. coli requires further post translational modifications (e.g. glycosylation) whereas yeasts are able to perform these modifications themselves by virtue of being more complex host organisms. The advantage of recombinant human insulin is after chronic use patients don't develop an immune defence against it the way animal sourced insulin stimulates the human immune system.
=== Recombinant human growth hormone (HGH, somatotropin) ===
Administered to patients whose pituitary glands generate insufficient quantities to support normal growth and development. Before recombinant HGH became available, HGH for therapeutic use was obtained from pituitary glands of cadavers. This unsafe practice led to some patients developing Creutzfeldt–Jakob disease. Recombinant HGH eliminated this problem, and is now used therapeutically. It has also been misused as a performance-enhancing drug by athletes and others.
=== Recombinant blood clotting factor VIII ===
It is the recombinant form of factor VIII, a blood-clotting protein that is administered to patients with the bleeding disorder hemophilia, who are unable to produce factor VIII in quantities sufficient to support normal blood coagulation. Before the development of recombinant factor VIII, the protein was obtained by processing large quantities of human blood from multiple donors, which carried a very high risk of transmission of blood borne infectious diseases, for example HIV and hepatitis B.
=== Recombinant hepatitis B vaccine ===
Hepatitis B infection can be successfully controlled through the use of a recombinant subunit hepatitis B vaccine, which contains a form of the hepatitis B virus surface antigen that is produced in yeast cells. The development of the recombinant subunit vaccine was an important and necessary development because hepatitis B virus, unlike other common viruses such as polio virus, cannot be grown in vitro.
=== Recombinant antibodies ===
Recombinant antibodies (rAbs) are produced in vitro by the means of expression systems based on mammalian cells. Their monospecific binding to a specific epitope makes rAbs eligible not only for research purposes, but also as therapy options against certain cancer types, infections and autoimmune diseases.
=== Diagnosis of HIV infection ===
Each of the three widely used methods for diagnosing HIV infection has been developed using recombinant DNA. The antibody test (ELISA or western blot) uses a recombinant HIV protein to test for the presence of antibodies that the body has produced in response to an HIV infection. The DNA test looks for the presence of HIV genetic material using reverse transcription polymerase chain reaction (RT-PCR). Development of the RT-PCR test was made possible by the molecular cloning and sequence analysis of HIV genomes. HIV testing page from US Centers for Disease Control (CDC)
=== Golden rice ===
Golden rice is a recombinant variety of rice that has been engineered to express the enzymes responsible for β-carotene biosynthesis. This variety of rice holds substantial promise for reducing the incidence of vitamin A deficiency in the world's population. Golden rice is not currently in use, pending the resolution of regulatory and intellectual property issues.
=== Herbicide-resistant crops ===
Commercial varieties of important agricultural crops (including soy, maize/corn, sorghum, canola, alfalfa and cotton) have been developed that incorporate a recombinant gene that results in resistance to the herbicide glyphosate (trade name Roundup), and simplifies weed control by glyphosate application. These crops are in common commercial use in several countries.
=== Insect-resistant crops ===
Bacillus thuringiensis is a bacterium that naturally produces a protein (Bt toxin) with insecticidal properties. The bacterium has been applied to crops as an insect-control strategy for many years, and this practice has been widely adopted in agriculture and gardening. Recently, plants have been developed that express a recombinant form of the bacterial protein, which may effectively control some insect predators. Environmental issues associated with the use of these transgenic crops have not been fully resolved.
== History ==
The idea of recombinant DNA was first proposed by Peter Lobban, a graduate student of Prof. Dale Kaiser in the Biochemistry Department at Stanford University Medical School. The first publications describing the successful production and intracellular replication of recombinant DNA appeared in 1972 and 1973, from Stanford and UCSF. In 1980 Paul Berg, a professor in the Biochemistry Department at Stanford and an author on one of the first papers was awarded the Nobel Prize in Chemistry for his work on nucleic acids "with particular regard to recombinant DNA". Werner Arber, Hamilton Smith, and Daniel Nathans shared the 1978 Nobel Prize in Physiology or Medicine for the discovery of restriction endonucleases which enhanced the techniques of rDNA technology.
Stanford University applied for a U.S. patent on recombinant DNA on November 4, 1974, listing the inventors as Herbert W. Boyer (professor at the University of California, San Francisco) and Stanley N. Cohen (professor at Stanford University); this patent, U.S. 4,237,224A, was awarded on December 2, 1980. The first licensed drug generated using recombinant DNA technology was human insulin, developed by Genentech and licensed by Eli Lilly and Company.
== Controversy ==
Scientists associated with the initial development of recombinant DNA methods recognized that the potential existed for organisms containing recombinant DNA to have undesirable or dangerous properties. At the 1975 Asilomar Conference on Recombinant DNA, these concerns were discussed and a voluntary moratorium on recombinant DNA research was initiated for experiments that were considered particularly risky. This moratorium was widely observed until the US National Institutes of Health developed and issued formal guidelines for rDNA work. Today, recombinant DNA molecules and recombinant proteins are usually not regarded as dangerous. However, concerns remain about some organisms that express recombinant DNA, particularly when they leave the laboratory and are introduced into the environment or food chain. These concerns are discussed in the articles on genetically modified organisms and genetically modified food controversies. Furthermore, there are concerns about the by-products in biopharmaceutical production, where recombinant DNA result in specific protein products. The major by-product, termed host cell protein, comes from the host expression system and poses a threat to the patient's health and the overall environment.
== See also ==
Asilomar conference on recombinant DNA
Genetic engineering
Genetically modified organism
Recombinant virus
Vector DNA
Biomolecular engineering
Recombinant DNA technology
Host cell protein
T7 expression system
== References ==
=== Further reading ===
The Eighth Day of Creation: Makers of the Revolution in Biology. Touchstone Books, ISBN 0-671-22540-5. 2nd edition: Cold Spring Harbor Laboratory Press, 1996 paperback: ISBN 0-87969-478-5.
Micklas, David. 2003. DNA Science: A First Course. Cold Spring Harbor Press: ISBN 978-0-87969-636-8.
Rasmussen, Nicolas, Gene Jockeys: Life Science and the rise of Biotech Enterprise, Johns Hopkins University Press, (Baltimore), 2014. ISBN 978-1-42141-340-2.
Rosenfeld, Israel. 2010. DNA: A Graphic Guide to the Molecule that Shook the World. Columbia University Press: ISBN 978-0-231-14271-7.
Schultz, Mark and Zander Cannon. 2009. The Stuff of Life: A Graphic Guide to Genetics and DNA. Hill and Wang: ISBN 0-8090-8947-5.
Watson, James. 2004. DNA: The Secret of Life. Random House: ISBN 978-0-09-945184-6.
== External links ==
Recombinant DNA fact sheet (from University of New Hampshire)
Plasmids in Yeasts (Fact sheet from San Diego State University)
Recombinant DNA research at UCSF and commercial application at Genentech Edited transcript of 1994 interview with Herbert W. Boyer, Living history project. Oral history.
Recombinant Protein Purification Principles and Methods Handbook Archived 2008-12-05 at the Wayback Machine
Massachusetts Institute of Technology, Oral History Program, Oral History Collection on the Recombinant DNA Controversy, MC-0100. Massachusetts Institute of Technology, Department of Distinctive Collections, Cambridge, Massachusetts | Wikipedia/Recombinant_DNA |
DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a strand's supercoiling affects a number of biological processes, such as compacting DNA and regulating access to the genetic code (which strongly affects DNA metabolism and possibly gene expression). Certain enzymes, such as topoisomerases, change the amount of DNA supercoiling to facilitate functions such as DNA replication and transcription. The amount of supercoiling in a given strand is described by a mathematical formula that compares it to a reference state known as "relaxed B-form" DNA.
== Overview ==
In a "relaxed" double-helical segment of B-DNA, the two strands twist around the helical axis once every 10.4–10.5 base pairs of sequence. Adding or subtracting twists, as some enzymes do, imposes strain. If a DNA segment under twist strain is closed into a circle by joining its two ends, and then allowed to move freely, it takes on different shape, such as a figure-eight. This shape is referred to as a supercoil. (The noun form "supercoil" is often used when describing DNA topology.)
The DNA of most organisms is usually negatively supercoiled. It becomes temporarily positively supercoiled when it is being replicated or transcribed. These processes are inhibited (regulated) if it is not promptly relaxed. The simplest shape of a supercoil is a figure eight; a circular DNA strand assumes this shape to accommodate more or few helical twists. The two lobes of the figure eight will appear rotated either clockwise or counterclockwise with respect to one another, depending on whether the helix is over- or underwound. For each additional helical twist being accommodated, the lobes will show one more rotation about their axis.
Lobal contortions of a circular DNA, such as the rotation of the figure-eight lobes above, are referred to as writhe. The above example illustrates that twist and writhe are interconvertible. Supercoiling can be represented mathematically by the sum of twist and writhe. The twist is the number of helical turns in the DNA and the writhe is the number of times the double helix crosses over on itself (these are the supercoils). Extra helical twists are positive and lead to positive supercoiling, while subtractive twisting causes negative supercoiling. Many topoisomerase enzymes sense supercoiling and either generate or dissipate it as they change DNA topology.
In part because chromosomes may be very large, segments in the middle may act as if their ends are anchored. As a result, they may be unable to distribute excess twist to the rest of the chromosome or to absorb twist to recover from underwinding—the segments may become supercoiled, in other words. In response to supercoiling, they will assume an amount of writhe, just as if their ends were joined.
Supercoiled DNA forms two structures; a plectoneme or a toroid, or a combination of both. A negatively supercoiled DNA molecule will produce either a one-start left-handed helix, the toroid, or a two-start right-handed helix with terminal loops, the plectoneme. Plectonemes are typically more common in nature, and this is the shape most bacterial plasmids will take. For larger molecules it is common for hybrid structures to form – a loop on a toroid can extend into a plectoneme. If all the loops on a toroid extend then it becomes a branch point in the plectonemic structure. DNA supercoiling is important for DNA packaging within all cells, and seems to also play a role in gene expression.
== Intercalation-induced supercoiling of DNA ==
Based on the properties of intercalating molecules, i.e. fluorescing upon binding to DNA and unwinding of DNA base-pairs, in 2016, a single-molecule technique has been introduced to directly visualize individual plectonemes along supercoiled DNA which would further allow to study the interactions of DNA processing proteins with supercoiled DNA. In that study, Sytox Orange (an intercalating dye) was used to induce supercoiling on surface tethered DNA molecules.
Using this assay, it was found that the DNA sequence encodes for the position of plectonemic supercoils. Furthermore, DNA supercoils were found to be enriched at the transcription start sites in prokaryotes.
== Functions ==
=== Genome packaging ===
DNA supercoiling is important for DNA packaging within all cells. Because the length of DNA can be thousands of times that of a cell, packaging this genetic material into the cell or nucleus (in eukaryotes) is a difficult feat. Supercoiling of DNA reduces the space and allows for DNA to be packaged. In prokaryotes, plectonemic supercoils are predominant, because of the circular chromosome and relatively small amount of genetic material. In eukaryotes, DNA supercoiling exists on many levels of both plectonemic and solenoidal supercoils, with the solenoidal supercoiling proving most effective in compacting the DNA. Solenoidal supercoiling is achieved with histones to form a 10 nm fiber. This fiber is further coiled into a 30 nm fiber, and further coiled upon itself numerous times more.
DNA packaging is greatly increased during mitosis when duplicated sister DNAs are segregated into daughter cells. It has been shown that condensin, a large protein complex that plays a central role in mitotic chromosome assembly, induces positive supercoils in an ATP hydrolysis-dependent manner in vitro. Supercoiling could also play an important role during interphase in the formation and maintenance of topologically associating domains (TADs).
Supercoiling is also required for DNA/RNA synthesis. Because DNA must be unwound for DNA/RNA polymerase action, supercoils will result. The region ahead of the polymerase complex will be unwound; this stress is compensated with positive supercoils ahead of the complex. Behind the complex, DNA is rewound and there will be compensatory negative supercoils. Topoisomerases such as DNA gyrase (Type II Topoisomerase) play a role in relieving some of the stress during DNA/RNA synthesis.
In many bacterial species, barriers to supercoil diffusion divide the genome into a series of topologically isolated supercoil domains (SDs). These SDs play a major role in organizing the nucleoid. SDs negatively supercoiled on average but can sometimes be positively supercoiled as well. The degree of supercoiling can vary in response to different forms of stress and influences the binding of different nucleoid associated proteins (NAPs) that further organize the bacterial genome. For example, Dps from E. coli has been shown to bind supercoiled DNA much more rapidly that torsionally relaxed DNA.
=== Gene expression ===
Specialized proteins can unzip small segments of the DNA molecule when it is replicated or transcribed into RNA. But work published in 2015 illustrates how DNA opens on its own.
Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Also, transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read. Unfortunately, these interactions are very difficult to study because biological molecules morph shapes so easily. In 2008 it was noted that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself affects how the molecule responds to supercoiling.
For example, the researchers identified a specific sequence of DNA that regulates transcription speed; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA. It is hypothesized that these structural changes might trigger stress elsewhere along its length, which in turn might provide trigger points for replication or gene expression. This implies that it is a very dynamic process in which both DNA and proteins each influences how the other acts and reacts.
=== Gene Expression during cold shock ===
Almost half of the genes of the bacterium E. coli that are repressed during cold shock are similarly repressed when Gyrase is blocked by the antibiotic Novobiocin. Moreover, during cold shocks, the density of nucleoids increases, and the protein gyrase and the nucleoid become colocalized (which is consistent with a reduction in DNA relaxation). This is evidence that the reduction of negative supercoiling of the DNA is one of the main mechanisms responsible for the blocking of transcription of half of the genes that conduct the cold shock transcriptional response program of bacteria. Based on this, a stochastic model of this process has been proposed. This model is illustrated in the figure, where reactions 1 represent transcription and its locking due to supercoiling. Meanwhile, reactions 2 to 4 model, respectively, translation, and RNA and protein degradation.
== Mathematical description ==
In nature, circular DNA is always isolated as a higher-order helix-upon-a-helix, known as a superhelix. In discussions of this subject, the Watson–Crick twist is referred to as a "secondary" winding, and the superhelices as a "tertiary" winding. The sketch on the left indicates a "relaxed", or "open circular" Watson–Crick double-helix, and, next to it, a right-handed superhelix. The "relaxed" structure on the left is not found unless the chromosome is nicked; the superhelix is the form usually found in nature.
For purposes of mathematical computations, a right-handed superhelix is defined as having a "negative" number of superhelical turns, and a left-handed superhelix is defined as having a "positive" number of superhelical turns. In the drawing (shown at the right), both the secondary (i.e., "Watson–Crick") winding and the tertiary (i.e., "superhelical") winding are right-handed, hence the supertwists are negative (–3 in this example).
The superhelicity is presumed to be a result of underwinding, meaning that there is a deficiency in the number of secondary Watson–Crick twists. Such a chromosome will be strained, just as a macroscopic metal spring is strained when it is either overwound or unwound. In DNA which is thusly strained, supertwists will appear.
DNA supercoiling can be described numerically by changes in the linking number Lk. The linking number is the most descriptive property of supercoiled DNA. Lko, the number of turns in the relaxed (B type) DNA plasmid/molecule, is determined by dividing the total base pairs of the molecule by the relaxed bp/turn which, depending on reference is 10.4; 10.5; 10.6.
L
k
o
=
b
p
/
10.4
{\displaystyle Lk_{o}=bp/10.4}
Lk is the number of crosses a single strand makes across the other, often visualized as the number of Watson–Crick twists found in a circular chromosome in a (usually imaginary) planar projection. This number is physically "locked in" at the moment of covalent closure of the chromosome, and cannot be altered without strand breakage.
The topology of the DNA is described by the equation below in which the linking number is equivalent to the sum of Tw, which is the number of twists or turns of the double helix, and Wr, which is the number of coils or "writhes." If there is a closed DNA molecule, the sum of Tw and Wr, or the linking number, does not change. However, there may be complementary changes in Tw and Wr without changing their sum:
L
k
=
T
w
+
W
r
{\displaystyle Lk=Tw+Wr}
Tw, called "twist," is the number of Watson–Crick twists in the chromosome when it is not constrained to lie in a plane. We have already seen that native DNA is usually found to be superhelical. If one goes around the superhelically twisted chromosome, counting secondary Watson–Crick twists, that number will be different from the number counted when the chromosome is constrained to lie flat. In general, the number of secondary twists in the native, supertwisted chromosome is expected to be the "normal" Watson–Crick winding number, meaning a single 10-base-pair helical twist for every 34 Å of DNA length.
Wr, called "writhe," is the number of superhelical twists. Since biological circular DNA is usually underwound, Lk will generally be less than Tw, which means that Wr will typically be negative.
If DNA is underwound, it will be under strain, exactly as a metal spring is strained when forcefully unwound, and that the appearance of supertwists will allow the chromosome to relieve its strain by taking on negative supertwists, which correct the secondary underwinding in accordance with the topology equation above.
The topology equation shows that there is a one-to-one relationship between changes in Tw and Wr. For example, if a secondary "Watson–Crick" twist is removed, then a right-handed supertwist must have been removed simultaneously (or, if the chromosome is relaxed, with no supertwists, then a left-handed supertwist must be added).
The change in the linking number, ΔLk, is the actual number of turns in the plasmid/molecule, Lk, minus the number of turns in the relaxed plasmid/molecule Lko:
Δ
L
k
=
L
k
−
L
k
o
{\displaystyle \Delta Lk=Lk-Lk_{o}}
If the DNA is negatively supercoiled,
Δ
L
k
<
0
{\displaystyle \Delta Lk<0}
. The negative supercoiling implies that the DNA is underwound.
A standard expression independent of the molecule size is the "specific linking difference" or "superhelical density" denoted σ, which represents the number of turns added or removed relative to the total number of turns in the relaxed molecule/plasmid, indicating the level of supercoiling.
σ
=
Δ
L
k
/
L
k
o
{\displaystyle \sigma =\Delta {Lk/Lk_{o}}}
The Gibbs free energy associated with the coiling is given by the equation below
Δ
G
/
N
=
10
R
T
σ
2
{\displaystyle {\Delta G/N=10RT\sigma ^{2}}}
The difference in Gibbs free energy between the supercoiled circular DNA and uncoiled circular DNA with N > 2000 bp is approximated by:
Δ
G
/
N
=
700
Kcal
/
b
p
∗
(
Δ
L
k
/
N
)
{\displaystyle \Delta G/N=700\,{\text{Kcal}}/bp*(\Delta Lk/N)}
or, 16 cal/bp.
Since the linking number L of supercoiled DNA is the number of times the two strands are intertwined (and both strands remain covalently intact), L cannot change. The reference state (or parameter) L0 of a circular DNA duplex is its relaxed state. In this state, its writhe W = 0. Since L = T + W, in a relaxed state T = L. Thus, if we have a 400 bp relaxed circular DNA duplex, L ~ 40 (assuming ~10 bp per turn in B-DNA). Then T ~ 40.
Positively supercoiling:
T = 0, W = 0, then L = 0
T = +3, W = 0, then L = +3
T = +2, W = +1, then L = +3
Negatively supercoiling:
T = 0, W = 0, then L = 0
T = -3, W = 0, then L = -3
T = -2, W = -1, then L = -3
Negative supercoils favor local unwinding of the DNA, allowing processes such as transcription, DNA replication, and recombination. Negative supercoiling is also thought to favour the transition between B-DNA and Z-DNA, and moderate the interactions of DNA binding proteins involved in gene regulation.
== Stochastic models ==
Some stochastic models have been proposed to account for the effects of positive supercoiling buildup (PSB) in gene expression dynamics (e.g. in bacterial gene expression), differing in, e.g., the level of detail. In general, the detail increases when adding processes affected by and affecting supercoiling. As this addition occurs, the complexity of the model increases.
For example, in two models of different complexity are proposed. In the most detailed one, events were modeled at the nucleotide level, while in the other the events were modeled at the promoter region alone, and thus required much less events to be accounted for.
Examples of stochastic models that focus on the effects of PSB on a promoter's activity can be found in:. In general, such models include a promoter, Pro, which is the region of DNA controlling transcription and, thus, whose activity/locking is affected by PSB. Also included are RNA molecules (the product of transcription), RNA polymerases (RNAP) which control transcription, and Gyrases (G) which regulate PSB. Finally, there needs to be a means to quantify PSB on the DNA (i.e. the promoter) at any given moment. This can be done by having some component in the system that is produced over time (e.g., during transcription events) to represent positive supercoils, and that is removed by the action of Gyrases. The amount of this component can then be set to affect the rate of transcription.
== Effects on sedimentation coefficient ==
The topological properties of circular DNA are complex. In standard texts, these properties are invariably explained in terms of a helical model for DNA, but in 2008 it was noted that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations.
When the sedimentation coefficient, s, of circular DNA is ascertained over a large range of pH, the following curves are seen. Three curves are shown here, representing three species of DNA. From top-to-bottom they are: "Form IV" (green), "Form I" (blue) and "Form II" (red).
"Form I" (blue curve) is the traditional nomenclature used for the native form of duplex circular DNA, as recovered from viruses and intracellular plasmids. Form I is covalently closed, and any plectonemic winding which may be present is therefore locked in. If one or more nicks are introduced to Form I, free rotation of one strand with respect to the other becomes possible, and Form II (red curve) is seen.
Form IV (green curve) is the product of alkali denaturation of Form I. Its structure is unknown, except that it is persistently duplex, and extremely dense.
Between pH 7 and pH 11.5, the sedimentation coefficient s, for Form I, is constant. Then it dips, and at a pH just below 12, reaches a minimum. With further increases in pH, s then returns to its former value. It doesn't stop there, however, but continues to increase relentlessly. By pH 13, the value of s has risen to nearly 50, two to three times its value at pH 7, indicating an extremely compact structure.
If the pH is then lowered, the s value is not restored. Instead, one sees the upper, green curve. The DNA, now in the state known as Form IV, remains extremely dense, even if the pH is restored to the original physiologic range. As stated previously, the structure of Form IV is almost entirely unknown, and there is no currently accepted explanation for its extraordinary density. About all that is known about the tertiary structure is that it is duplex, but has no hydrogen bonding between bases.
These behaviors of Forms I and IV are considered to be due to the peculiar properties of duplex DNA which has been covalently closed into a double-stranded circle. If the covalent integrity is disrupted by even a single nick in one of the strands, all such topological behavior ceases, and one sees the lower Form II curve (Δ). For Form II, alterations in pH have very little effect on s. Its physical properties are, in general, identical to those of linear DNA. At pH 13, the strands of Form II simply separate, just as the strands of linear DNA do. The separated single strands have slightly different s values, but display no significant changes in s with further increases in pH.
A complete explanation for these data is beyond the scope of this article. In brief, the alterations in s come about because of changes in the superhelicity of circular DNA. These changes in superhelicity are schematically illustrated by four little drawings which have been strategically superimposed upon the figure above.
Briefly, the alterations of s seen in the pH titration curve above are widely thought to be due to changes in the superhelical winding of DNA under conditions of increasing pH. Up to pH 11.5, the purported "underwinding" produces a right-handed ("negative") supertwist. But as the pH increases, and the secondary helical structure begins to denature and unwind, the chromosome (if we may speak anthropomorphically) no longer "wants" to have the full Watson–Crick winding, but rather "wants", increasingly, to be "underwound". Since there is less and less strain to be relieved by superhelical winding, the superhelices therefore progressively disappear as the pH increases. At a pH just below 12, all incentive for superhelicity has expired, and the chromosome will appear as a relaxed, open circle.
At higher pH still, the chromosome, which is now denaturing in earnest, tends to unwind entirely, which it cannot do so (because Lk is covalently locked in). Under these conditions, what was once treated as "underwinding" has actually now become "overwinding". Once again there is strain, and once again it is (in part at least) relieved by superhelicity, but this time in the opposite direction (i.e., left-handed or "positive"). Each left-handed tertiary supertwist removes a single, now undesirable right-handed Watson–Crick secondary twist.
The titration ends at pH 13, where Form IV appears.
== See also ==
Mechanical properties of DNA
Ribbon theory
== References ==
=== Further reading === | Wikipedia/DNA_supercoil |
Arsenic biochemistry is the set of biochemical processes that can use arsenic or its compounds, such as arsenate. Arsenic is a moderately abundant element in Earth's crust, and although many arsenic compounds are often considered highly toxic to most life, a wide variety of organoarsenic compounds are produced biologically and various organic and inorganic arsenic compounds are metabolized by numerous organisms. This pattern is general for other related elements, including selenium, which can exhibit both beneficial and deleterious effects. Arsenic biochemistry has become topical since many toxic arsenic compounds are found in some aquifers, potentially affecting many millions of people via biochemical processes.
== Sources of arsenic ==
=== Organoarsenic compounds in nature ===
The evidence that arsenic may be a beneficial nutrient at trace levels below the background to which living organisms are normally exposed has been reviewed. Some organoarsenic compounds found in nature are arsenobetaine and arsenocholine, both being found in many marine organisms. Some As-containing nucleosides (sugar derivatives) are also known. Several of these organoarsenic compounds arise via methylation processes. For example, the mold Scopulariopsis brevicaulis produces significant amounts of trimethylarsine if inorganic arsenic is present. The organic compound arsenobetaine is found in some marine foods such as fish and algae, and also in mushrooms in larger concentrations. In clean environments, the edible mushroom species Cyanoboletus pulverulentus hyperaccumulates arsenic in concentrations reaching even 1,300 mg/kg in dry weight; cacodylic acid is the major As compound. A very unusual composition of organoarsenic compounds was found in deer truffles (Elaphomyces spp.). The average person's intake is about 10–50 μg/day. Values about 1000 μg are not unusual following consumption of fish or mushrooms; however, there is little danger in eating fish since this arsenic compound is nearly non-toxic.
Representative organoarsenic compounds found in nature.
A topical source of arsenic are the green pigments once popular in wallpapers, e.g. Paris green. A variety of illness have been blamed on this compound, although its toxicity has been exaggerated.
Trimethylarsine, once known as Gosio's gas, is an intensely malodorous organoarsenic compound that is commonly produced by microbial action on inorganic arsenic substrates.
Arsenic (V) compounds are easily reduced to arsenic (III) and could have served as an electron acceptor on primordial Earth. Lakes that contain a substantial amount of dissolved inorganic arsenic, harbor arsenic-tolerant biota.
=== Incorrect claims of arsenic-based life (phosphorus substitution) ===
Although phosphate and arsenate are structurally similar, there is no evidence that arsenic replaces phosphorus in DNA or RNA. A 2010 experiment involving the bacterium GFAJ-1 that made this claim was refuted by 2012.
=== Anthropogenic arsenic compounds ===
Anthropogenic (man-made) sources of arsenic, like the natural sources, are mainly arsenic oxides and the associated anions. Man-made sources of arsenic, include wastes from mineral processing, swine and poultry farms. For example, many ores, especially sulfide minerals, are contaminated with arsenic, which is released in roasting (burning in air). In such processing, arsenide is converted to arsenic trioxide, which is volatile at high temperatures and is released into the atmosphere. Poultry and swine farms make heavy use of the organoarsenic compound roxarsone as an antibiotic in feed. Some wood is treated with copper arsenates as a preservative. The mechanisms by which these sources affect "downstream" living organisms remains uncertain but are probably diverse. One commonly cited pathway involves methylation.
The monomethylated acid, methanearsonic acid (CH3AsO(OH)2), is a precursor to fungicides (tradename Neoasozin) in the cultivation of rice and cotton. Derivatives of phenylarsonic acid (C6H5AsO(OH)2) are used as feed additives for livestock, including 4-hydroxy-3-nitrobenzenearsonic acid (3-NHPAA or Roxarsone), ureidophenylarsonic acid, and p-arsanilic acid. These applications are controversial as they introduce soluble forms of arsenic into the environment.
==== Arsenic-based drugs ====
Despite, or possibly because of, its long-known toxicity, arsenic-containing potions and drugs have a history in medicine and quackery that continues into the 21st century. Starting in the early 19th century and continuing into the 20th century, Fowler's solution, a toxic concoction of sodium arsenite, was sold. The organoarsenic compound Salvarsan was the first synthetic chemotherapeutic agent, discovered by Paul Ehrlich. The treatment, however, led to many problems causing long lasting health complications. Around 1943 it was finally superseded by penicillin.
The related drug Melarsoprol is still in use against late-state African trypanosomiasis (sleeping sickness), despite its high toxicity and possibly fatal side effects.
Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis (programmed cell death) in certain types of cancer cells, which are normally immortal and can multiply without limit. In combination with all-trans retinoic acid, it is FDA-approved as first-line treatment for promyelocytic leukemia.
== Methylation of arsenic ==
Inorganic arsenic and its compounds, upon entering the food chain, are progressively metabolised (detoxified) through a process of methylation. The methylation occurs through alternating reductive and oxidative methylation reactions, that is, reduction of pentavalent to trivalent arsenic followed by addition of a methyl group (CH3).
In mammals, methylation occurs in the liver by methyltransferases, the products being the (CH3)2AsOH (dimethylarsinous acid) and (CH3)2As(O)OH (dimethylarsinic acid), which have the oxidation states As(III) and As(V), respectively. Although the mechanism of methylation of arsenic in humans has not been elucidated, the source of methyl is methionine, which suggests a role of S-adenosyl methionine. Exposure to toxic doses begin when the liver's methylation capacity is exceeded or inhibited.
There are two major forms of arsenic that can enter the body, arsenic (III) and arsenic (V). Arsenic (III) enters the cells though aquaporins 7 and 9, which is a type of aquaglyceroporin. Arsenic (V) compounds use phosphate transporters to enter cells. The arsenic (V) can be converted to arsenic (III) by the enzyme purine nucleoside phosphorylase. This is classified as a bioactivation step, as although arsenic (III) is more toxic, it is more readily methylated.
There are two routes by which inorganic arsenic compounds are methylated. The first route uses Cyt19 arsenic methyltransferase to methylate arsenic (III) to a mono-methylated arsenic (V) compound. This compound is then converted to a mono-methylated arsenic (III) compound using Glutathione S-Transferase Omega-1 (GSTO1). The mono-methylated arsenic (V) compound can then be methylated again by Cyt19 arsenic methyltransferase, which forms a dimethyl arsenic (V) compound, which can be converted to a dimethyl arsenic (III) compound by Glutathione S-Transferase Omega-1 (GTSO1). The other route uses glutathione (GSH) to conjugate with arsenic (III) to form an arsenic (GS) 3 complex. This complex can form a monomethylated arsenic (III) GS complex, using Cyt19 arsenic methyltransferase, and this monomethylated GS complex is in equilibrium with the monomethylated arsenic (III). Cyt19 arsenic methyltransferase can methylate the complex one more time, and this forms a dimethylated arsenic GS complex, which is in equilibrium with a dimethyl arsenic (III) complex. Both of the mono-methylated and di-methylated arsenic compounds can readily be excreted in urine. However, the monomethylated compound was shown to be more reactive and more toxic than the inorganic arsenic compounds to human hepatocytes (liver), keratinocytes in the skin, and bronchial epithelial cells (lungs).
Studies in experimental animals and humans show that both inorganic arsenic and methylated metabolites cross the placenta to the fetus, however, there is evidence that methylation is increased during pregnancy and that it could be highly protective for the developing organism.
Enzymatic methylation of arsenic is a detoxification process; it can be methylated to methylarsenite, dimethylarsenite or trimethylarsenite, all of which are trivalent. The methylation is catalyzed by arsenic methyltransferase (AS3MT) in mammals, which transfers a methyl group on the cofactor S-adenomethionine (SAM) to arsenic (III). An orthologue of AS3MT is found in bacteria and is called CmArsM. This enzyme was tested in three states (ligand free, arsenic (III) bound and SAM bound). Arsenic (III) binding sites usually use thiol groups of cysteine residues. The catalysis involves thiolates of Cys72, Cys174, and Cys224. In an SN2 reaction, the positive charge on the SAM sulfur atom pulls the bonding electron from the carbon of the methyl group, which interacts with the arsenic lone pair to form an As−C bond, leaving SAH.
=== Excretion ===
In humans, the major route of excretion of most arsenic compounds is via the urine. The biological half-life of inorganic arsenic is about 4 days, but is slightly shorter following exposure to arsenate than to arsenite. The main metabolites excreted in the urine of humans exposed to inorganic arsenic are mono- and dimethylated arsenic acids, together with some unmetabolized inorganic arsenic.
The biotransformation of arsenic for excretion is primarily done through the nuclear factor erythroid 2 related factor 2 (Nrf2) pathway. Under normal conditions the Nrf2 is bound to Kelch-like ECH associated protein 1 (Keap1) in its inactive form. With the uptake of arsenic within cells and the subsequent reactions that result in the production of reactive oxygen species (ROS), the Nrf2 unbinds and becomes active. Keap1 has reactive thiol moieties that bind ROS or electrophilic arsenic species such as monomethylted arsenic (III) and induces the release of Nrf2 which then travels through the cytoplasm to the nucleus. The Nrf2 then activates antioxidant responsive element (ARE) as well as electrophilic responsive element (EpRE) both of which contribute in the increase of antioxidant proteins. Of particular note in these antioxidant proteins is heme oxygenase 1 ([HO-1]), NAD(P)H-quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthase (γGCS) which work in conjunction to reduce the oxidative species such as hydrogen peroxide to decrease the oxidative stress upon the cell. The increase in γGCS causes an increased production of arsenite triglutathionine (As(SG)3) an important adduct that is taken up by either multidrug associated protein 1 or 2 (MRP1 or MRP2) which removes the arsenic out of the cell and into bile for excretion. This adduct can also decompose back into inorganic arsenic.
Of particular note in the excretion of arsenic is the multiple methylation steps that take place which may increase the toxicity of arsenic due to MMeAsIII being a potent inhibitor of glutathione peroxidase, glutathione reductase, pyruvate dehydrogenase, and thioredoxin reductase.
== Arsenic toxicity ==
Arsenic is a cause of mortality throughout the world; associated problems include heart, respiratory, gastrointestinal, liver, nervous and kidney diseases.
Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase (PDH) complex, which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD+. With the enzyme inhibited, the energy system of the cell is disrupted resulting in a cellular apoptosis episode. Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis.
Genotoxicity involves inhibition of DNA repair and DNA methylation. The carcinogenic effect of arsenic arises from the oxidative stress induced by arsenic. Arsenic's high toxicity naturally led to the development of a variety of arsenic compounds as chemical weapons, e.g. dimethylarsenic chloride. Some were employed as chemical warfare agents, especially in World War I. This threat led to many studies on antidotes and an expanded knowledge of the interaction of arsenic compounds with living organisms. One result was the development of antidotes such as British anti-Lewisite. Many such antidotes exploit the affinity of As(III) for thiolate ligands, which convert highly toxic organoarsenicals to less toxic derivatives. It is generally assumed that arsenates bind to cysteine residues in proteins.
By contrast, arsenic oxide is an approved and effective chemotherapeutic drug for the treatment of acute promyelocytic leukemia (APL).
=== Toxicity of pentavalent arsenicals ===
Due to its similar structure and properties, pentavalent arsenic metabolites are capable of replacing the phosphate group of many metabolic pathways. The replacement of phosphate by arsenate is initiated when arsenate reacts with glucose and gluconate in vitro. This reaction generates glucose-6-arsenate and 6-arsenogluconate, which act as analogs for glucose-6-phosphate and 6-phosphogluconate. At the substrate level, during glycolysis, glucose-6-arsenate binds as a substrate to glucose-6-phosphate dehydrogenase, and also inhibits hexokinase through negative feedback. Unlike the importance of phosphate in glycolysis, the presence of arsenate restricts the generation of ATP by forming an unstable anhydride product, through the reaction with D-glyceraldehyde-3-phosphate. The anhydride 1-arsenato-3-phospho-D-glycerate generated readily hydrolyzes due to the longer bond length of As-O compared to P-O. At the mitochondrial level, arsenate uncouples the synthesis of ATP by binding to ADP in the presence of succinate, thus forming an unstable compound that ultimately results in a decrease of ATP net gain. Arsenite (III) metabolites, on the other hand, have limited effect on ATP production in red blood cells.
=== Toxicity of trivalent arsenicals ===
Enzymes and receptors that contain thiol or sulfhydryl functional groups are actively targeted by arsenite (III) metabolites. These sulfur-containing compounds are normally glutathione and the amino acid cysteine. Arsenite derivatives generally have higher binding affinity compared to the arsenate metabolites. These bindings restrict activity of certain metabolic pathways. For example, pyruvate dehydrogenase (PDH) is inhibited when monomethylarsonous acid (MMAIII) targets the thiol group of the lipoic acid cofactor. PDH is a precursor of acetyl-CoA, thus the inhibition of PDH eventually limits the production of ATP in electron transport chain, as well as the production of gluconeogenesis intermediates.
=== Oxidative stress ===
Arsenic can cause oxidative stress through the formation of reactive oxygen species (ROS), and reactive nitrogen species (RNS). Reactive oxygen species are produced by the enzyme NADPH oxidase, which transfers electrons from NADPH to oxygen, synthesizing a superoxide, which is a reactive free radical. This superoxide can react to form hydrogen peroxide and a reactive oxygen species. The enzyme NADPH oxidase is able to generate more reactive oxygen species in the presence of arsenic, due to the subunit p22phox, which is responsible for the electron transfer, being upregulated by arsenic. The reactive oxygen species are capable of stressing the endoplasmic reticulum, which increases the amount of the unfolded protein response signals. This leads to inflammation, cell proliferation, and eventually to cell death. Another mechanism in which reactive oxygen species cause cell death would be through the cytoskeleton rearrangement, which affects the contractile proteins.
The reactive nitrogen species arise once the reactive oxygen species destroy the mitochondria. This leads to the formation of the reactive nitrogen species, which are responsible for damaging DNA in arsenic poisoning. Mitochondrial damage is known to cause the release of reactive nitrogen species, due to the reaction between superoxides and nitric oxide (NO). Nitric oxide (NO) is a part of cell regulation, including cellular metabolism, growth, division and death. Nitric oxide (NO) reacts with reactive oxygen species to form peroxynitrite. In cases of chronic arsenic exposure, the nitric oxide levels are depleted, due to the superoxide reactions. The enzyme NO synthase (NOS) uses L-arginine to form nitric oxide, but this enzyme is inhibited by monomethylated arsenic (III) compounds.
=== DNA damage ===
Arsenic is reported to cause DNA modifications such as aneuploidy, micronuclei formation, chromosome abnormality, deletion mutations, sister chromatid exchange and crosslinking of DNA with proteins. It has been demonstrated that arsenic does not directly interact with DNA and it is considered a poor mutagen, but instead, it helps mutagenicity of other carcinogens. For instance, a synergistic increase in the mutagenic activity of arsenic with UV light has been observed in human and other mammalian cells after exposing the UV-treated cells to arsenic. A series of experimental observations suggest that the arsenic genotoxicity is primarily linked to the generation of reactive oxygen species (ROS) during its biotransformation. The ROS production is able to generate DNA adducts, DNA strand breaks, crosslinks and chromosomal aberrations. The oxidative damage is caused by modification of DNA nucleobases, in particular 8-oxoguanine (8-OHdG) which leads to G:C to T:A mutations. Inorganic arsenic can also cause DNA strand break even at low concentrations.
==== Inhibition of DNA repair ====
Inhibition of DNA repair processes is considered one of main mechanism of inorganic arsenic genotoxicity. Nucleotide excision repair (NER) and base excision repair (BER) are the processes implicated in the repair of DNA base damage induced by ROS after arsenic exposure. In particular, the NER mechanism is the major pathway for repairing bulky distortions in DNA double helix, while the BER mechanism is mainly implicated in the repair of single strand breaks induced by ROS, but inorganic arsenic could also repress the BER mechanism.
Exposure of isolated lymphocytes to arsenic causes decreased expression of the DNA repair protein ERCC1. Consistent with an inhibitory effect on DNA repair, lymphocytes from arsenic exposed individuals have higher levels of DNA damage. Arsenic can act as a co-carcinogen by inhibiting repair of DNA damage through its interaction with sensitive zinc finger DNA repair proteins.
=== Neurodegenerative mechanisms ===
Arsenic is highly detrimental to the innate and the adaptive immune system of the body. When the amount of unfolded and misfolded proteins in endoplasmic reticulum stress is excessive, the unfolded protein response (UPR) is activated to increase the activity of several receptors that are responsible the restoration of homeostasis. The inositol-requiring enzyme-1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) are two receptors that restrict the rate of translation. On the other hand, the unfolded proteins are corrected by the production of chaperones, which are induced by the activating transcription factor 6 (ATF6). If the number of erroneous proteins elevates, further mechanism is active which triggers apoptosis. Arsenic has evidentially shown to increase the activity of these protein sensors.
=== Immune dysfunction ===
Arsenic exposure in small children distorts the ratio of T helper cells (CD4) to cytotoxic T cells (CD8), which are responsible for immunodepression. In addition, arsenic also increases the number of inflammatory molecules being secreted through macrophages. The excess amount of granulocytes and monocytes lead to a chronic state of inflammation, which might result in cancer development.
== Arsenic poisoning treatment ==
There are three molecules that serve as chelator agents that bond to arsenic. These three are British Anti-Lewisite (BAL, Dimercaprol), succimer (DMSA) and Unithiol (DMPS).
When these agents chelate inorganic arsenic, it is converted into an organic form of arsenic because it is bound to the organic chelating agent. The sulfur atoms of the thiol groups are the site of interaction with arsenic. This is because the thiol groups are nucleophilic while the arsenic atoms are electrophilic. Once bound to the chelating agent the molecules can be excreted, and therefore free inorganic arsenic atoms are removed from the body.
Other chelating agents can be used, but may cause more side effects than British Anti-Lewisite (BAL, Dimercaprol), succimer (DMSA) and (DMPS). DMPS and DMSA also have a higher therapeutic index than BAL.
These drugs are efficient for acute poisoning of arsenic, which refers to the instantaneous effects caused by arsenic poisoning. For example, headaches, vomiting or sweating are some of the common examples of an instantaneous effect. In comparison, chronic poisonous effects arise later on, and unexpectedly such as organ damage. Usually it is too late to prevent them once they appear. Therefore, action should be taken as soon as acute poisonous effects arise.
== See also ==
Arsenic compounds
Extremophile
Geomicrobiology
Hypothetical types of biochemistry
Organoarsenic chemistry
== References == | Wikipedia/Arsenic_DNA |
DNA nanotechnology is the design and manufacture of artificial nucleic acid structures for technological uses. In this field, nucleic acids are used as non-biological engineering materials for nanotechnology rather than as the carriers of genetic information in living cells. Researchers in the field have created static structures such as two- and three-dimensional crystal lattices, nanotubes, polyhedra, and arbitrary shapes, and functional devices such as molecular machines and DNA computers. The field is beginning to be used as a tool to solve basic science problems in structural biology and biophysics, including applications in X-ray crystallography and nuclear magnetic resonance spectroscopy of proteins to determine structures. Potential applications in molecular scale electronics and nanomedicine are also being investigated.
The conceptual foundation for DNA nanotechnology was first laid out by Nadrian Seeman in the early 1980s, and the field began to attract widespread interest in the mid-2000s. This use of nucleic acids is enabled by their strict base pairing rules, which cause only portions of strands with complementary base sequences to bind together to form strong, rigid double helix structures. This allows for the rational design of base sequences that will selectively assemble to form complex target structures with precisely controlled nanoscale features. Several assembly methods are used to make these structures, including tile-based structures that assemble from smaller structures, folding structures using the DNA origami method, and dynamically reconfigurable structures using strand displacement methods. The field's name specifically references DNA, but the same principles have been used with other types of nucleic acids as well, leading to the occasional use of the alternative name nucleic acid nanotechnology.
== History ==
The conceptual foundation for DNA nanotechnology was first laid out by Nadrian Seeman in the early 1980s. Seeman's original motivation was to create a three-dimensional DNA lattice for orienting other large molecules, which would simplify their crystallographic study by eliminating the difficult process of obtaining pure crystals. This idea had reportedly come to him in late 1980, after realizing the similarity between the woodcut Depth by M. C. Escher and an array of DNA six-arm junctions. Several natural branched DNA structures were known at the time, including the DNA replication fork and the mobile Holliday junction, but Seeman's insight was that immobile nucleic acid junctions could be created by properly designing the strand sequences to remove symmetry in the assembled molecule, and that these immobile junctions could in principle be combined into rigid crystalline lattices. The first theoretical paper proposing this scheme was published in 1982, and the first experimental demonstration of an immobile DNA junction was published the following year.
In 1991, Seeman's laboratory published a report on the synthesis of a cube made of DNA, the first synthetic three-dimensional nucleic acid nanostructure, for which he received the 1995 Feynman Prize in Nanotechnology. This was followed by a DNA truncated octahedron. It soon became clear that these structures, polygonal shapes with flexible junctions as their vertices, were not rigid enough to form extended three-dimensional lattices. Seeman developed the more rigid double-crossover (DX) structural motif, and in 1998, in collaboration with Erik Winfree, published the creation of two-dimensional lattices of DX tiles. These tile-based structures had the advantage that they provided the ability to implement DNA computing, which was demonstrated by Winfree and Paul Rothemund in their 2004 paper on the algorithmic self-assembly of a Sierpinski gasket structure, and for which they shared the 2006 Feynman Prize in Nanotechnology. Winfree's key insight was that the DX tiles could be used as Wang tiles, meaning that their assembly could perform computation. The synthesis of a three-dimensional lattice was finally published by Seeman in 2009, nearly thirty years after he had set out to achieve it.
New abilities continued to be discovered for designed DNA structures throughout the 2000s. The first DNA nanomachine—a motif that changes its structure in response to an input—was demonstrated in 1999 by Seeman. An improved system, which was the first nucleic acid device to make use of toehold-mediated strand displacement, was demonstrated by Bernard Yurke in 2000. The next advance was to translate this into mechanical motion, and in 2004 and 2005, several DNA walker systems were demonstrated by the groups of Seeman, Niles Pierce, Andrew Turberfield, and Chengde Mao. The idea of using DNA arrays to template the assembly of other molecules such as nanoparticles and proteins, first suggested by Bruche Robinson and Seeman in 1987, was demonstrated in 2002 by Seeman, Kiehl et al. and subsequently by many other groups.
In 2006, Rothemund first demonstrated the DNA origami method for easily and robustly forming folded DNA structures of arbitrary shape. Rothemund had conceived of this method as being conceptually intermediate between Seeman's DX lattices, which used many short strands, and William Shih's DNA octahedron, which consisted mostly of one very long strand. Rothemund's DNA origami contains a long strand which folding is assisted by several short strands. This method allowed forming much larger structures than formerly possible, and which are less technically demanding to design and synthesize. DNA origami was the cover story of Nature on March 15, 2006. Rothemund's research demonstrating two-dimensional DNA origami structures was followed by the demonstration of solid three-dimensional DNA origami by Douglas et al. in 2009, while the labs of Jørgen Kjems and Yan demonstrated hollow three-dimensional structures made out of two-dimensional faces.
DNA nanotechnology was initially met with some skepticism due to the unusual non-biological use of nucleic acids as materials for building structures and doing computation, and the preponderance of proof of principle experiments that extended the abilities of the field but were far from actual applications. Seeman's 1991 paper on the synthesis of the DNA cube was rejected by the journal Science after one reviewer praised its originality while another criticized it for its lack of biological relevance. By the early 2010s the field was considered to have increased its abilities to the point that applications for basic science research were beginning to be realized, and practical applications in medicine and other fields were beginning to be considered feasible. The field had grown from very few active laboratories in 2001 to at least 60 in 2010, which increased the talent pool and thus the number of scientific advances in the field during that decade.
== Fundamental concepts ==
=== Properties of nucleic acids ===
Nanotechnology is often defined as the study of materials and devices with features on a scale below 100 nanometers. DNA nanotechnology, specifically, is an example of bottom-up molecular self-assembly, in which molecular components spontaneously organize into stable structures; the particular form of these structures is induced by the physical and chemical properties of the components selected by the designers. In DNA nanotechnology, the component materials are strands of nucleic acids such as DNA; these strands are often synthetic and are almost always used outside the context of a living cell. DNA is well-suited to nanoscale construction because the binding between two nucleic acid strands depends on simple base pairing rules which are well understood, and form the specific nanoscale structure of the nucleic acid double helix. These qualities make the assembly of nucleic acid structures easy to control through nucleic acid design. This property is absent in other materials used in nanotechnology, including proteins, for which protein design is very difficult, and nanoparticles, which lack the capability for specific assembly on their own.
The structure of a nucleic acid molecule consists of a sequence of nucleotides distinguished by which nucleobase they contain. In DNA, the four bases present are adenine (A), cytosine (C), guanine (G), and thymine (T). Nucleic acids have the property that two molecules will only bind to each other to form a double helix if the two sequences are complementary, meaning that they form matching sequences of base pairs, with A only binding to T, and C only to G. Because the formation of correctly matched base pairs is energetically favorable, nucleic acid strands are expected in most cases to bind to each other in the conformation that maximizes the number of correctly paired bases. The sequences of bases in a system of strands thus determine the pattern of binding and the overall structure in an easily controllable way. In DNA nanotechnology, the base sequences of strands are rationally designed by researchers so that the base pairing interactions cause the strands to assemble in the desired conformation. While DNA is the dominant material used, structures incorporating other nucleic acids such as RNA and peptide nucleic acid (PNA) have also been constructed.
=== Subfields ===
DNA nanotechnology is sometimes divided into two overlapping subfields: structural DNA nanotechnology and dynamic DNA nanotechnology. Structural DNA nanotechnology, sometimes abbreviated as SDN, focuses on synthesizing and characterizing nucleic acid complexes and materials that assemble into a static, equilibrium end state. On the other hand, dynamic DNA nanotechnology focuses on complexes with useful non-equilibrium behavior such as the ability to reconfigure based on a chemical or physical stimulus. Some complexes, such as nucleic acid nanomechanical devices, combine features of both the structural and dynamic subfields.
The complexes constructed in structural DNA nanotechnology use topologically branched nucleic acid structures containing junctions. (In contrast, most biological DNA exists as an unbranched double helix.) One of the simplest branched structures is a four-arm junction that consists of four individual DNA strands, portions of which are complementary in a specific pattern. Unlike in natural Holliday junctions, each arm in the artificial immobile four-arm junction has a different base sequence, causing the junction point to be fixed at a certain position. Multiple junctions can be combined in the same complex, such as in the widely used double-crossover (DX) structural motif, which contains two parallel double helical domains with individual strands crossing between the domains at two crossover points. Each crossover point is, topologically, a four-arm junction, but is constrained to one orientation, in contrast to the flexible single four-arm junction, providing a rigidity that makes the DX motif suitable as a structural building block for larger DNA complexes.
Dynamic DNA nanotechnology uses a mechanism called toehold-mediated strand displacement to allow the nucleic acid complexes to reconfigure in response to the addition of a new nucleic acid strand. In this reaction, the incoming strand binds to a single-stranded toehold region of a double-stranded complex, and then displaces one of the strands bound in the original complex through a branch migration process. The overall effect is that one of the strands in the complex is replaced with another one. In addition, reconfigurable structures and devices can be made using functional nucleic acids such as deoxyribozymes and ribozymes, which can perform chemical reactions, and aptamers, which can bind to specific proteins or small molecules.
== Structural DNA nanotechnology ==
Structural DNA nanotechnology, sometimes abbreviated as SDN, focuses on synthesizing and characterizing nucleic acid complexes and materials where the assembly has a static, equilibrium endpoint. The nucleic acid double helix has a robust, defined three-dimensional geometry that makes it possible to simulate, predict and design the structures of more complicated nucleic acid complexes. Many such structures have been created, including two- and three-dimensional structures, and periodic, aperiodic, and discrete structures.
=== Extended lattices ===
Small nucleic acid complexes can be equipped with sticky ends and combined into larger two-dimensional periodic lattices containing a specific tessellated pattern of the individual molecular tiles. The earliest example of this used double-crossover (DX) complexes as the basic tiles, each containing four sticky ends designed with sequences that caused the DX units to combine into periodic two-dimensional flat sheets that are essentially rigid two-dimensional crystals of DNA. Two-dimensional arrays have been made from other motifs as well, including the Holliday junction rhombus lattice, and various DX-based arrays making use of a double-cohesion scheme. The top two images at right show examples of tile-based periodic lattices.
Two-dimensional arrays can be made to exhibit aperiodic structures whose assembly implements a specific algorithm, exhibiting one form of DNA computing. The DX tiles can have their sticky end sequences chosen so that they act as Wang tiles, allowing them to perform computation. A DX array whose assembly encodes an XOR operation has been demonstrated; this allows the DNA array to implement a cellular automaton that generates a fractal known as the Sierpinski gasket. The third image at right shows this type of array. Another system has the function of a binary counter, displaying a representation of increasing binary numbers as it grows. These results show that computation can be incorporated into the assembly of DNA arrays.
DX arrays have been made to form hollow nanotubes 4–20 nm in diameter, essentially two-dimensional lattices which curve back upon themselves. These DNA nanotubes are somewhat similar in size and shape to carbon nanotubes, and while they lack the electrical conductance of carbon nanotubes, DNA nanotubes are more easily modified and connected to other structures. One of many schemes for constructing DNA nanotubes uses a lattice of curved DX tiles that curls around itself and closes into a tube. In an alternative method that allows the circumference to be specified in a simple, modular fashion using single-stranded tiles, the rigidity of the tube is an emergent property.
Forming three-dimensional lattices of DNA was the earliest goal of DNA nanotechnology, but this proved to be one of the most difficult to realize. Success using a motif based on the concept of tensegrity, a balance between tension and compression forces, was finally reported in 2009.
=== Discrete structures ===
Researchers have synthesized many three-dimensional DNA complexes that each have the connectivity of a polyhedron, such as a cube or octahedron, meaning that the DNA duplexes trace the edges of a polyhedron with a DNA junction at each vertex. The earliest demonstrations of DNA polyhedra were very work-intensive, requiring multiple ligations and solid-phase synthesis steps to create catenated polyhedra. Subsequent work yielded polyhedra whose synthesis was much easier. These include a DNA octahedron made from a long single strand designed to fold into the correct conformation, and a tetrahedron that can be produced from four DNA strands in one step, pictured at the top of this article.
Nanostructures of arbitrary, non-regular shapes are usually made using the DNA origami method. These structures consist of a long, natural virus strand as a "scaffold", which is made to fold into the desired shape by computationally designed short "staple" strands. This method has the advantages of being easy to design, as the base sequence is predetermined by the scaffold strand sequence, and not requiring high strand purity and accurate stoichiometry, as most other DNA nanotechnology methods do. DNA origami was first demonstrated for two-dimensional shapes, such as a smiley face, a coarse map of the Western Hemisphere, and the Mona Lisa painting. Solid three-dimensional structures can be made by using parallel DNA helices arranged in a honeycomb pattern, and structures with two-dimensional faces can be made to fold into a hollow overall three-dimensional shape, akin to a cardboard box. These can be programmed to open and reveal or release a molecular cargo in response to a stimulus, making them potentially useful as programmable molecular cages.
=== Templated assembly ===
Nucleic acid structures can be made to incorporate molecules other than nucleic acids, sometimes called heteroelements, including proteins, metallic nanoparticles, quantum dots, amines, and fullerenes. This allows the construction of materials and devices with a range of functionalities much greater than is possible with nucleic acids alone. The goal is to use the self-assembly of the nucleic acid structures to template the assembly of the nanoparticles hosted on them, controlling their position and in some cases orientation.
Many of these schemes use a covalent attachment scheme, using oligonucleotides with amide or thiol functional groups as a chemical handle to bind the heteroelements. This covalent binding scheme has been used to arrange gold nanoparticles on a DX-based array,
and to arrange streptavidin protein molecules into specific patterns on a DX array.
A non-covalent hosting scheme using Dervan polyamides on a DX array was used to arrange streptavidin proteins in a specific pattern on a DX array. Carbon nanotubes have been hosted on DNA arrays in a pattern allowing the assembly to act as a molecular electronic device, a carbon nanotube field-effect transistor. In addition, there are nucleic acid metallization methods, in which the nucleic acid is replaced by a metal which assumes the general shape of the original nucleic acid structure, and schemes for using nucleic acid nanostructures as lithography masks, transferring their pattern into a solid surface.
== Dynamic DNA nanotechnology ==
Dynamic DNA nanotechnology focuses on forming nucleic acid systems with designed dynamic functionalities related to their overall structures, such as computation and mechanical motion. There is some overlap between structural and dynamic DNA nanotechnology, as structures can be formed through annealing and then reconfigured dynamically, or can be made to form dynamically in the first place.
=== Nanomechanical devices ===
DNA complexes have been made that change their conformation upon some stimulus, making them one form of nanorobotics. These structures are initially formed in the same way as the static structures made in structural DNA nanotechnology, but are designed so that dynamic reconfiguration is possible after the initial assembly. The earliest such device made use of the transition between the B-DNA and Z-DNA forms to respond to a change in buffer conditions by undergoing a twisting motion.
This reliance on buffer conditions caused all devices to change state at the same time. Subsequent systems could change states based upon the presence of control strands, allowing multiple devices to be independently operated in solution. Some examples of such systems are a "molecular tweezers" design that has an open and a closed state, a device that could switch from a paranemic-crossover (PX) conformation to a (JX2) conformation with two non-junction juxtapositions of the DNA backbone, undergoing rotational motion in the process, and a two-dimensional array that could dynamically expand and contract in response to control strands. Structures have also been made that dynamically open or close, potentially acting as a molecular cage to release or reveal a functional cargo upon opening. In another example, a DNA origami nanostructure was coupled to T7 RNA polymerase and could thus be operated as a chemical energy-driven motor that can be coupled to a passive follower, which it then drives.
DNA walkers are a class of nucleic acid nanomachines that exhibit directional motion along a linear track. A large number of schemes have been demonstrated. One strategy is to control the motion of the walker along the track using control strands that need to be manually added in sequence. It is also possible to control individual steps of a DNA walker by irradiation with light of different wavelengths. Another approach is to make use of restriction enzymes or deoxyribozymes to cleave the strands and cause the walker to move forward, which has the advantage of running autonomously. A later system could walk upon a two-dimensional surface rather than a linear track, and demonstrated the ability to selectively pick up and move molecular cargo. In 2018, a catenated DNA that uses rolling circle transcription by an attached T7 RNA polymerase was shown to walk along a DNA-path, guided by the generated RNA strand. Additionally, a linear walker has been demonstrated that performs DNA-templated synthesis as the walker advances along the track, allowing autonomous multistep chemical synthesis directed by the walker. The synthetic DNA walkers' function is similar to that of the proteins dynein and kinesin.
=== Strand displacement cascades ===
Cascades of strand displacement reactions can be used for either computational or structural purposes. An individual strand displacement reaction involves revealing a new sequence in response to the presence of some initiator strand. Many such reactions can be linked into a cascade where the newly revealed output sequence of one reaction can initiate another strand displacement reaction elsewhere. This in turn allows for the construction of chemical reaction networks with many components, exhibiting complex computational and information processing abilities. These cascades are made energetically favorable through the formation of new base pairs, and the entropy gain from disassembly reactions. Strand displacement cascades allow isothermal operation of the assembly or computational process, in contrast to traditional nucleic acid assembly's requirement for a thermal annealing step, where the temperature is raised and then slowly lowered to ensure proper formation of the desired structure. They can also support catalytic function of the initiator species, where less than one equivalent of the initiator can cause the reaction to go to completion.
Strand displacement complexes can be used to make molecular logic gates capable of complex computation. Unlike traditional electronic computers, which use electric current as inputs and outputs, molecular computers use the concentrations of specific chemical species as signals. In the case of nucleic acid strand displacement circuits, the signal is the presence of nucleic acid strands that are released or consumed by binding and unbinding events to other strands in displacement complexes. This approach has been used to make logic gates such as AND, OR, and NOT gates. More recently, a four-bit circuit was demonstrated that can compute the square root of the integers 0–15, using a system of gates containing 130 DNA strands.
Another use of strand displacement cascades is to make dynamically assembled structures. These use a hairpin structure for the reactants, so that when the input strand binds, the newly revealed sequence is on the same molecule rather than disassembling. This allows new opened hairpins to be added to a growing complex. This approach has been used to make simple structures such as three- and four-arm junctions and dendrimers.
== Applications ==
DNA nanotechnology provides one of the few ways to form designed, complex structures with precise control over nanoscale features. The field is beginning to see application to solve basic science problems in structural biology and biophysics. The earliest such application envisaged for the field, and one still in development, is in crystallography, where molecules that are difficult to crystallize in isolation could be arranged within a three-dimensional nucleic acid lattice, allowing determination of their structure. Another application is the use of DNA origami rods to replace liquid crystals in residual dipolar coupling experiments in protein NMR spectroscopy; using DNA origami is advantageous because, unlike liquid crystals, they are tolerant of the detergents needed to suspend membrane proteins in solution. DNA walkers have been used as nanoscale assembly lines to move nanoparticles and direct chemical synthesis. Further, DNA origami structures have aided in the biophysical studies of enzyme function and protein folding.
DNA nanotechnology is moving toward potential real-world applications. The ability of nucleic acid arrays to arrange other molecules indicates its potential applications in molecular scale electronics. The assembly of a nucleic acid structure could be used to template the assembly of molecular electronic elements such as molecular wires, providing a method for nanometer-scale control of the placement and overall architecture of the device analogous to a molecular breadboard. DNA nanotechnology has been compared to the concept of programmable matter because of the coupling of computation to its material properties.
In a study conducted by a group of scientists from iNANO and CDNA centers in Aarhus University, researchers were able to construct a small multi-switchable 3D DNA Box Origami. The proposed nanoparticle was characterized by atomic force microscopy (AFM), transmission electron microscopy (TEM) and Förster resonance energy transfer (FRET). The constructed box was shown to have a unique reclosing mechanism, which enabled it to repeatedly open and close in response to a unique set of DNA or RNA keys. The authors proposed that this "DNA device can potentially be used for a broad range of applications such as controlling the function of single molecules, controlled drug delivery, and molecular computing."
There are potential applications for DNA nanotechnology in nanomedicine, making use of its ability to perform computation in a biocompatible format to make "smart drugs" for targeted drug delivery, as well as for diagnostic applications. One such system being investigated uses a hollow DNA box containing proteins that induce apoptosis, or cell death, that will only open when in proximity to a cancer cell. There has additionally been interest in expressing these artificial structures in engineered living bacterial cells, most likely using the transcribed RNA for the assembly, although it is unknown whether these complex structures are able to efficiently fold or assemble in the cell's cytoplasm. If successful, this could enable directed evolution of nucleic acid nanostructures.
Scientists at Oxford University reported the self-assembly of four short strands of synthetic DNA into a cage which can enter cells and survive for at least 48 hours. The fluorescently labeled DNA tetrahedra were found to remain intact in the laboratory cultured human kidney cells despite the attack by cellular enzymes after two days. This experiment showed the potential of drug delivery inside the living cells using the DNA ‘cage’. A DNA tetrahedron was used to deliver RNA Interference (RNAi) in a mouse model, reported a team of researchers in MIT. Delivery of the interfering RNA for treatment has showed some success using polymer or lipid, but there are limits of safety and imprecise targeting, in addition to short shelf life in the blood stream. The DNA nanostructure created by the team consists of six strands of DNA to form a tetrahedron, with one strand of RNA affixed to each of the six edges. The tetrahedron is further equipped with targeting protein, three folate molecules, which lead the DNA nanoparticles to the abundant folate receptors found on some tumors. The result showed that the gene expression targeted by the RNAi, luciferase, dropped by more than half. This study shows promise in using DNA nanotechnology as an effective tool to deliver treatment using the emerging RNA Interference technology. The DNA tetrahedron was also used in an effort to overcome the phenomena multidrug resistance. Doxorubicin (DOX) was conjugated with the tetrahedron and was loaded into MCF-7 breast cancer cells that contained the P-glycoprotein drug efflux pump. The results of the experiment showed the DOX was not being pumped out and apoptosis of the cancer cells was achieved. The tetrahedron without DOX was loaded into cells to test its biocompatibility, and the structure showed no cytotoxicity itself. The DNA tetrahedron was also used as barcode for profiling the subcellular expression and distribution of proteins in cells for diagnostic purposes. The tetrahedral-nanostructured showed enhanced signal due to higher labeling efficiency and stability.
Applications for DNA nanotechnology in nanomedicine also focus on mimicking the structure and function of naturally occurring membrane proteins with designed DNA nanostructures. In 2012, Langecker et al. introduced a pore-shaped DNA origami structure that can self-insert into lipid membranes via hydrophobic cholesterol modifications and induce ionic currents across the membrane. This first demonstration of a synthetic DNA ion channel was followed by a variety of pore-inducing designs ranging from a single DNA duplex, to small tile-based structures, and large DNA origami transmembrane porins. Similar to naturally occurring protein ion channels, this ensemble of synthetic DNA-made counterparts thereby spans multiple orders of magnitude in conductance. The study of the membrane-inserting single DNA duplex showed that current must also flow on the DNA-lipid interface as no central channel lumen is present in the design that lets ions pass across the lipid bilayer. This indicated that the DNA-induced lipid pore has a toroidal shape, rather than cylindrical, as lipid headgroups reorient to face towards the membrane-inserted part of the DNA. Researchers from the University of Cambridge and the University of Illinois at Urbana-Champaign then demonstrated that such a DNA-induced toroidal pore can facilitate rapid lipid flip-flop between the lipid bilayer leaflets. Utilizing this effect, they designed a synthetic DNA-built enzyme that flips lipids in biological membranes orders of magnitudes faster than naturally occurring proteins called scramblases. This development highlights the potential of synthetic DNA nanostructures for personalized drugs and therapeutics.
== Design ==
DNA nanostructures must be rationally designed so that individual nucleic acid strands will assemble into the desired structures. This process usually begins with specification of a desired target structure or function. Then, the overall secondary structure of the target complex is determined, specifying the arrangement of nucleic acid strands within the structure, and which portions of those strands should be bound to each other. The last step is the primary structure design, which is the specification of the actual base sequences of each nucleic acid strand.
=== Structural design ===
The first step in designing a nucleic acid nanostructure is to decide how a given structure should be represented by a specific arrangement of nucleic acid strands. This design step determines the secondary structure, or the positions of the base pairs that hold the individual strands together in the desired shape. Several approaches have been demonstrated:
Tile-based structures. This approach breaks the target structure into smaller units with strong binding between the strands contained in each unit, and weaker interactions between the units. It is often used to make periodic lattices, but can also be used to implement algorithmic self-assembly, making them a platform for DNA computing. This was the dominant design strategy used from the mid-1990s until the mid-2000s, when the DNA origami methodology was developed.
Folding structures. An alternative to the tile-based approach, folding approaches make the nanostructure from one long strand, which can either have a designed sequence that folds due to its interactions with itself, or it can be folded into the desired shape by using shorter, "staple" strands. This latter method is called DNA origami, which allows forming nanoscale two- and three-dimensional shapes (see Discrete structures above).
Dynamic assembly. This approach directly controls the kinetics of DNA self-assembly, specifying all of the intermediate steps in the reaction mechanism in addition to the final product. This is done using starting materials which adopt a hairpin structure; these then assemble into the final conformation in a cascade reaction, in a specific order (see Strand displacement cascades below). This approach has the advantage of proceeding isothermally, at a constant temperature. This is in contrast to the thermodynamic approaches, which require a thermal annealing step where a temperature change is required to trigger the assembly and favor proper formation of the desired structure.
=== Sequence design ===
After any of the above approaches are used to design the secondary structure of a target complex, an actual sequence of nucleotides that will form into the desired structure must be devised. Nucleic acid design is the process of assigning a specific nucleic acid base sequence to each of a structure's constituent strands so that they will associate into a desired conformation. Most methods have the goal of designing sequences so that the target structure has the lowest energy, and is thus the most thermodynamically favorable, while incorrectly assembled structures have higher energies and are thus disfavored. This is done either through simple, faster heuristic methods such as sequence symmetry minimization, or by using a full nearest-neighbor thermodynamic model, which is more accurate but slower and more computationally intensive. Geometric models are used to examine tertiary structure of the nanostructures and to ensure that the complexes are not overly strained.
Nucleic acid design has similar goals to protein design. In both, the sequence of monomers is designed to favor the desired target structure and to disfavor other structures. Nucleic acid design has the advantage of being much computationally easier than protein design, because the simple base pairing rules are sufficient to predict a structure's energetic favorability, and detailed information about the overall three-dimensional folding of the structure is not required. This allows the use of simple heuristic methods that yield experimentally robust designs. Nucleic acid structures are less versatile than proteins in their function because of proteins' increased ability to fold into complex structures, and the limited chemical diversity of the four nucleotides as compared to the twenty proteinogenic amino acids.
== Materials and methods ==
The sequences of the DNA strands making up a target structure are designed computationally, using molecular modeling and thermodynamic modeling software. The nucleic acids themselves are then synthesized using standard oligonucleotide synthesis methods, usually automated in an oligonucleotide synthesizer, and strands of custom sequences are commercially available. Strands can be purified by denaturing gel electrophoresis if needed, and precise concentrations determined via any of several nucleic acid quantitation methods using ultraviolet absorbance spectroscopy.
The fully formed target structures can be verified using native gel electrophoresis, which gives size and shape information for the nucleic acid complexes. An electrophoretic mobility shift assay can assess whether a structure incorporates all desired strands. Fluorescent labeling and Förster resonance energy transfer (FRET) are sometimes used to characterize the structure of the complexes.
Nucleic acid structures can be directly imaged by atomic force microscopy, which is well suited to extended two-dimensional structures, but less useful for discrete three-dimensional structures because of the microscope tip's interaction with the fragile nucleic acid structure; transmission electron microscopy and cryo-electron microscopy are often used in this case. Extended three-dimensional lattices are analyzed by X-ray crystallography.
== See also ==
International Society for Nanoscale Science, Computation, and Engineering
Comparison of nucleic acid simulation software
Molecular models of DNA
Nanobiotechnology
== References ==
== Further reading ==
General:
Specific subfields:
== External links ==
What is Bionanotechnology?—a video introduction to DNA nanotechnology | Wikipedia/DNA_nanotechnology |
Environmental DNA or eDNA is DNA that is collected from a variety of environmental samples such as soil, seawater, snow or air, rather than directly sampled from an individual organism. As various organisms interact with the environment, DNA is expelled and accumulates in their surroundings from various sources. Such eDNA can be sequenced by environmental omics to reveal facts about the species that are present in an ecosystem — even microscopic ones not otherwise apparent or detectable.
In recent years, eDNA has been used as a tool to detect endangered wildlife that were otherwise unseen. In 2020, human health researchers began repurposing eDNA techniques to track the COVID-19 pandemic.
Example sources of eDNA include, but are not limited to, feces, mucus, gametes, shed skin, carcasses and hair. Samples can be analyzed by high-throughput DNA sequencing methods, known as metagenomics, metabarcoding, and single-species detection, for rapid monitoring and measurement of biodiversity. In order to better differentiate between organisms within a sample, DNA metabarcoding is used in which the sample is analyzed and uses previously studied DNA libraries, such as BLAST, to determine what organisms are present.
eDNA metabarcoding is a novel method of assessing biodiversity wherein samples are taken from the environment via water, sediment or air from which DNA is extracted, and then amplified using general or universal primers in polymerase chain reaction and sequenced using next-generation sequencing to generate thousands to millions of reads. From this data, species presence can be determined, and overall biodiversity assessed. It is an interdisciplinary method that brings together traditional field-based ecology with in-depth molecular methods and advanced computational tools.
The analysis of eDNA has great potential, not only for monitoring common species, but to genetically detect and identify other extant species that could influence conservation efforts. This method allows for biomonitoring without requiring collection of the living organism, creating the ability to study organisms that are invasive, elusive, or endangered without introducing anthropogenic stress on the organism. Access to this genetic information makes a critical contribution to the understanding of population size, species distribution, and population dynamics for species not well documented. Importantly, eDNA is often more cost-effective compared to traditional sampling methods. The integrity of eDNA samples is dependent upon its preservation within the environment.
Soil, permafrost, freshwater and seawater are well-studied macro environments from which eDNA samples have been extracted, each of which include many more conditioned subenvironments. Because of its versatility, eDNA is applied in many subenvironments such as freshwater sampling, seawater sampling, terrestrial soil sampling (tundra permafrost), aquatic soil sampling (river, lake, pond, and ocean sediment), or other environments where normal sampling procedures can become problematic.
On 7 December 2022 a study in Nature reported the recovery of two-million year old eDNA in sediments from Greenland, which is currently considered the oldest DNA sequenced so far.
== Overview ==
Environmental DNA or eDNA describes the genetic material present in environmental samples such as sediment, water, and air, including whole cells, extracellular DNA and potentially whole organisms. The analysis of eDNA starts with capturing an environmental sample of interest. The DNA in the sample is then extracted and purified. The purified DNA is then amplified for a specific gene target so it can be sequenced and categorised based on its sequence. From this information, detection and classification of species is possible.
eDNA can come from skin, mucous, saliva, sperm, secretions, eggs, feces, urine, blood, roots, leaves, fruit, pollen, and rotting bodies of larger organisms, while microorganisms may be obtained in their entirety. eDNA production is dependent on biomass, age and feeding activity of the organism as well as physiology, life history, and space use.
Despite being a relatively new method of surveying, eDNA has already proven to have enormous potential in biological monitoring. Conventional methods for surveying richness and abundance are limited by taxonomic identification, may cause disturbance or destruction of habitat, and may rely on methods in which it is difficult to detect small or elusive species, thus making estimates for entire communities impossible. eDNA can complement these methods by targeting different species, sampling greater diversity, and increasing taxonomic resolution. Additionally, eDNA is capable of detecting rare species, but not of determining population quality information such as sex ratios and body conditions, so it is ideal for supplementing traditional studies. Regardless, it has useful applications in detecting the first occurrences of invasive species, the continued presence of native species thought to be extinct or otherwise threatened, and other elusive species occurring in low densities that would be difficult to detect by traditional means.
Degradation of eDNA in the environment limits the scope of eDNA studies, as often only small segments of genetic material remain, particularly in warm, tropical regions. Additionally, the varying lengths of time to degradation based on environmental conditions and the potential of DNA to travel throughout media such as water can affect inference of fine-scale spatiotemporal trends of species and communities. Despite these drawbacks, eDNA still has the potential to determine relative or rank abundance as some studies have found it to correspond with biomass, though the variation inherent in environmental samples makes it difficult to quantify. While eDNA has numerous applications in conservation, monitoring, and ecosystem assessment, as well as others yet to be described, the highly variable concentrations of eDNA and potential heterogeneity through the water body makes it essential that the procedure is optimized, ideally with a pilot study for each new application to ensure that the sampling design is appropriate to detect the target.
=== Community DNA ===
While the definition of eDNA seems straightforward, the lines between different forms of DNA become blurred, particularly in comparison to community DNA, which is described as bulk organismal samples. A question arises regarding whole microorganisms captured in eDNA samples: do these organisms alter the classification of the sample to a community DNA sample? Additionally, the classification of genetic material from feces is problematic and often referred to as eDNA. Differentiation between the two is important as community DNA indicates organismal presence at a particular time and place, while eDNA may have come from a different location, from predator feces, or from past presence, however this differentiation is often impossible. However, eDNA can be loosely classified as including many sectors of DNA biodiversity research, including fecal analysis and bulk samples when they are applicable to biodiversity research and ecosystem analysis.
=== selfDNA ===
The concept of selfDNA stems from discoveries made by scientists from the University of Naples Federico II, which were reported during 2015 in the journal New Phytologist, about the self-inhibitory effect of extracellular DNA in plants, but also in bacteria, fungi, algae, plants, protozoa and insects. The environmental source of such extracellular DNA is proposed to be plant litter but also other sources in different ecosystems and organisms, with the size of DNA fragments experimentally shown to have an inhibitory effect upon their conspecific organisms typically ranging between 200 and 500 base pairs. The selfDNA phenomenon has been postulated to drive ecological interactions and to be mechanistically mediated by damage-associated molecular patterns (DAMPs) and to have potential for the development of biocidal applications.
== eDNA metabarcoding ==
By 2019 methods in eDNA research had been expanded to be able to assess whole communities from a single sample. This process involves metabarcoding, which can be precisely defined as the use of general or universal polymerase chain reaction (PCR) primers on mixed DNA samples from any origin followed by high-throughput next-generation sequencing (NGS) to determine the species composition of the sample. This method has been common in microbiology for years, but is only just finding its footing in assessment of macroorganisms. Ecosystem-wide applications of eDNA metabarcoding have the potential to not only describe communities and biodiversity, but also to detect interactions and functional ecology over large spatial scales, though it may be limited by false readings due to contamination or other errors. Altogether, eDNA metabarcoding increases speed, accuracy, and identification over traditional barcoding and decreases cost, but needs to be standardized and unified, integrating taxonomy and molecular methods for full ecological study.
eDNA metabarcoding has applications to diversity monitoring across all habitats and taxonomic groups, ancient ecosystem reconstruction, plant-pollinator interactions, diet analysis, invasive species detection, pollution responses, and air quality monitoring. eDNA metabarcoding is a unique method still in development and will likely remain in flux for some time as technology advances and procedures become standardized. However, as metabarcoding is optimized and its use becomes more widespread, it is likely to become an essential tool for ecological monitoring and global conservation study.
== Extracellular and relic DNA ==
Extracellular DNA, sometimes called relic DNA, is DNA from dead microbes. Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer; it may provide nutrients; and it may act as a buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress.
Under the name of environmental DNA, eDNA has seen increased use in the natural sciences as a survey tool for ecology, monitoring the movements and presence of species in water, air, or on land, and assessing an area's biodiversity.
In the diagram on the right, the amount of relic DNA in a microbial environment is determined by inputs associated with the mortality of viable individuals with intact DNA and by losses associated with the degradation of relic DNA. If the diversity of sequences contained in the relic DNA pool is sufficiently different from that in the intact DNA pool, then relic DNA may bias estimates of microbial biodiversity (as indicated by different colored boxes) when sampling from the total (intact + relic) DNA pool. Standardised Data on Initiatives (STARDIT) has been proposed as one way of standardising both data about sampling and analysis methods, and taxonomic and ontological relationships.
== Collection ==
=== Terrestrial sediments ===
Methods in modern and ancient marine genomics
The importance of eDNA analysis stemmed from the recognition of the limitations presented by culture-based studies. Organisms have adapted to thrive in the specific conditions of their natural environments. Although scientists work to mimic these environments, many microbial organisms can not be removed and cultured in a laboratory setting. The earliest version of this analysis began with ribosomal RNA (rRNA) in microbes to better understand microbes that live in hostile environments. The genetic makeup of some microbes is then only accessible through eDNA analysis. Analytical techniques of eDNA were first applied to terrestrial sediments yielding DNA from both extinct and extant mammals, birds, insects and plants. Samples extracted from these terrestrial sediments are commonly referenced as 'sedimentary ancient DNA' (sedaDNA or dirtDNA). The eDNA analysis can also be used to study current forest communities including everything from birds and mammals to fungi and worms. Samples can be obtained from soil, faeces, 'bite DNA' from where leaves have been bitten, plants and leaves where animals have been, and from the blood meals of captured mosquitos which may have eaten blood from any animals in the area. Some methods can also attempt to capture cells with hair traps and sandpaper in areas commonly transversed by target species.
=== Aquatic sediments ===
The sedaDNA was subsequently used to study ancient animal diversity and verified using known fossil records in aquatic sediments. The aquatic sediments are deprived of oxygen and are thus protect the DNA from degrading. Other than ancient studies, this approach can be used to understand current animal diversity with relatively high sensitivity. While typical water samples can have the DNA degrade relatively quickly, the aquatic sediment samples can have useful DNA two months after the species was present. One problem with aquatic sediments is that it is unknown where the organism deposited the eDNA as it could have moved in the water column.
=== Aquatic (water column) ===
Studying eDNA in the water column can indicate the community composition of a body of water. Before eDNA, the main ways to study open water diversity were to use fishing and trapping, which require resources such as funding and skilled labour, whereas eDNA only needs samples of water. This method is effective as pH of the water does not affect the DNA as much as previously thought, and sensitivity can be increased relatively easily. Sensitivity is how likely the DNA marker will be present in the sampled water, and can be increased simply by taking more samples, having bigger samples, and increasing PCR. eDNA degrades relatively fast in the water column, which is very beneficial in short term conservation studies such as identifying what species are present.
Researchers at the Experimental Lakes Area in Ontario, Canada and McGill University have found that eDNA distribution reflects lake stratification. As seasons and water temperature change, water density also changes such that it forms distinct layers in small boreal lakes in the summer and winter. These layers mix during the spring and fall. Fish habitat use correlates to stratification (e.g. a cold-water fish like lake trout will stay in cold water) and so does eDNA distribution, as these researchers found.
== Monitoring species ==
eDNA can be used to monitor species throughout the year and can be very useful in conservation monitoring. eDNA analysis has been successful at identifying many different taxa from aquatic plants, aquatic mammals, fishes, mussels, fungi and even parasites. eDNA has been used to study species while minimizing any stress inducing human interaction, allowing researchers to monitor species presence at larger spatial scales more efficiently. The most prevalent use in current research is using eDNA to study the locations of species at risk, invasive species, and keystone species across all environments. eDNA is especially useful for studying species with small populations because eDNA is sensitive enough to confirm the presence of a species with relatively little effort to collect data which can often be done with a soil sample or water sample. eDNA relies on the efficiency of genomic sequencing and analysis as well as the survey methods used which continue to become more efficient and cheaper. Some studies have shown that eDNA sampled from stream and inshore environments decayed to undetectable levels within about 48 hours.
Environmental DNA can be applied as a tool to detect low abundance organisms in both active and passive forms. Active eDNA surveys target individual species or groups of taxa for detection by using highly sensitive species-specific quantitative real-time PCR or digital droplet PCR markers. CRISPR-Cas methodology has also been applied to the detection of single species from eDNA; utilising the Cas12a enzyme and allowing greater specificity when detecting sympatric taxa. Passive eDNA surveys employ massively-parallel DNA sequencing to amplify all eDNA molecules in a sample with no a priori target in mind, providing blanket DNA evidence of biotic community composition.
=== Decline of terrestrial arthropods ===
Differentiation of arthropod communities by plant species
Terrestrial arthropods are experiencing massive decline in Europe as well as globally, although only a fraction of the species have been assessed and the majority of insects are still undescribed to science. As one example, grassland ecosystems are home to diverse taxonomic and functional groups of terrestrial arthropods, such as pollinators, phytophagous insects, and predators, that use nectar and pollen for food sources, and stem and leaf tissue for food and development. These communities harbor endangered species, since many habitats have disappeared or are under significant threat. Therefore, extensive efforts are being conducted in order to restore European grassland ecosystems and conserve biodiversity. For instance, pollinators like bees and butterflies represent an important ecological group that has undergone severe decline in Europe, indicating a dramatic loss of grassland biodiversity. The vast majority of flowering plants are pollinated by insects and other animals both in temperate regions and the tropics. The majority of insect species are herbivores feeding on different parts of plants, and most of these are specialists, relying on one or a few plant species as their main food resource. However, given the gap in knowledge on existing insect species, and the fact that most species are still undescribed, it is clear that for the majority of plant species in the world, there is limited knowledge about the arthropod communities they harbor and interact with.
Terrestrial arthropod communities have traditionally been collected and studied using methods, such as Malaise traps and pitfall traps, which are very effective but somewhat cumbersome and potentially invasive methods. In some instances, these techniques fall short of performing efficient and standardized surveys, due to, for example, phenotypic plasticity, closely related species, and difficulties in identifying juvenile stages. Furthermore, morphological identification depends directly on taxonomic expertise, which is in decline. All such limitations of traditional biodiversity monitoring have created a demand for alternative approaches. Meanwhile, the advance in DNA sequencing technologies continuously provides new means of obtaining biological data. Hence, several new molecular approaches have recently been suggested for obtaining fast and efficient data on arthropod communities and their interactions through non‐invasive genetic techniques. This includes extracting DNA from sources such as bulk samples or insect soups, empty leaf mines, spider webs, pitcher plant fluid, environmental samples like soil, water, air, and even whole flowers (environmental DNA [eDNA]), host plant and predatory diet identification from insect DNA extracts, and predator scat from bats. Recently, also DNA from pollen attached to insects has been used for retrieving information on plant–pollinator interactions. Many of such recent studies rely on DNA metabarcoding—high‐throughput sequencing of PCR amplicons using generic primers.
=== Mammals ===
==== Snow tracks ====
Wildlife researchers in snowy areas also use snow samples to gather and extract genetic information about species of interest. DNA from snow track samples has been used to confirm the presence of such elusive and rare species as polar bears, arctic fox, lynx, wolverines, and fishers.
==== DNA from the air ====
In 2021, researchers demonstrated that eDNA can be collected from air and used to identify mammals. In 2023, scientists developed a specialized sampling probe and aircraft surveys to assess biodiversity of multiple taxa, including mammals, using air eDNA.
=== Managing fisheries ===
The successful management of commercial fisheries relies on standardised surveys to estimate the quantity and distribution of fish stocks. Atlantic cod (Gadus morhua) is an iconic example that demonstrates how poorly constrained data and uninformed decision making can result in catastrophic stock decline and ensuing economic and social problems. Traditional stock assessments of demersal fish species have relied primarily on trawl surveys, which have provided a valuable stream of information to decision makers. However, there are some notable drawbacks of demersal trawl surveys including cost, gear selectivity/catchability, habitat destruction and restricted coverage (e.g. hard-substrate bottom environments, marine protected areas).
Environmental DNA (eDNA) has emerged as a potentially powerful alternative for studying ecosystem dynamics. The constant loss and shedding of genetic material from macroorganisms imparts a molecular footprint in environmental samples that can be analysed to determine either the presence of specific target species or characterise biodiversity. The combination of next generation sequencing and eDNA sampling has been successfully applied in aquatic systems to document spatial and temporal patterns in the diversity of fish fauna. To further develop the utility of eDNA for fisheries management, understanding the ability of eDNA quantities to reflect fish biomass in the ocean is an important next step.
Positive relationships between eDNA quantities and fish biomass and abundance have been demonstrated in experimental systems. However, known variations between eDNA production and degradation rates are anticipated to complicate these relationships in natural systems. Furthermore, in oceanic systems, large habitat volumes and strong currents are likely to result in physical dispersal of DNA fragments away from target organisms. These confounding factors have been previously considered to restrict the application of quantitative eDNA monitoring in oceanic settings.
Despite these potential constraints, numerous studies in marine environments have found positive relationships between eDNA quantities and complimentary survey efforts including radio-tagging, visual surveys, echo-sounding and trawl surveys. However, studies that quantify target eDNA concentrations of commercial fish species with standardised trawl surveys in marine environments are much scarcer. In this context, direct comparisons of eDNA concentrations with biomass and stock assessment metrics, such as catch per unit effort (CPUE), are necessary to understand the applicability of eDNA monitoring to contribute to fisheries management efforts.
== Deep sea sediments ==
Extracellular DNA in surface deep-sea sediments is by far the largest reservoir of DNA of the world oceans. The main sources of extracellular DNA in such ecosystems are represented by in situ DNA release from dead benthic organisms, and/or other processes including cell lysis due to viral infection, cellular exudation and excretion from viable cells, virus decomposition, and allochthonous inputs from the water column. Previous studies provided evidence that an important fraction of extracellular DNA can escape degradation processes, remaining preserved in the sediments. This DNA represents, potentially, a genetic repository that records biological processes occurring over time.
Recent investigations revealed that DNA preserved in marine sediments is characterized by a large number of highly diverse gene sequences. In particular, extracellular DNA has been used to reconstruct past prokaryotic and eukaryotic diversity in benthic ecosystems characterized by low temperatures and/or permanently anoxic conditions.
The diagram on the right shows the OTU (operational taxonomic unit) network of the extracellular DNA pools from the sediments of the different continental margins. The dot size within the network is proportional to the abundance of sequences for each OTU. Dots circled in red represent extracellular core OTUs, dot circled in yellow are partially shared (among two or more pools) OTUs, dots circled in black are OTUs exclusive of each pool. The core OTUs contributing at least for 20 sequences are shown. The numbers in parentheses represent the number of connections among OTUs and samples: 1 for exclusive OTUs, 2–3 for partially shared OTUs and 4 for core OTUs.
Previous studies suggested that the preservation of DNA might be also favoured in benthic systems characterised by high organic matter inputs and sedimentation rates, such as continental margins. These systems, which represent ca. 15% of the global seafloor, are also hotspots of benthic prokaryotic diversity, and therefore they could represent optimal sites to investigate the prokaryotic diversity preserved within extracellular DNA.
Spatial distribution of prokaryotic diversity has been intensively studied in benthic deep-sea ecosystems through the analysis of "environmental DNA" (i.e., the genetic material obtained directly from environmental samples without any obvious signs of biological source material). However, the extent to which gene sequences contained within extracellular DNA can alter the estimates of the diversity of the present-day prokaryotic assemblages is unknown.
== Sedimentary ancient DNA ==
Analyses of ancient DNA preserved in various archives have transformed understanding of the evolution of species and ecosystems. Whilst earlier studies have concentrated on DNA extracted from taxonomically constrained samples (such as bones or frozen tissue), advances in high-throughput sequencing and bioinformatics now allow the analysis of ancient DNA extracted from sedimentary archives, so called sedaDNA. The accumulation and preservation of sedaDNA buried in land and lake sediments have been subject to active research and interpretation. However, studying the deposition of DNA on the ocean floor and its preservation in marine sediments is more complex because the DNA has to travel through a water column for several kilometers. Unlike in the terrestrial environment, with pervasive transport of subfossil biomass from land, the largest portion of the marine sedaDNA is derived from planktonic community, which is dominated by marine microbes and marine protists. After the death of the surface plankton, its DNA is subject to a transport through the water column, during which much of the associated organic matter is known to be consumed and respired. This transport could take between 3 and 12 days depending on the size and morphology of test. However, it remains unclear how exactly the planktonic eDNA, defined as the total DNA present in the environment after, survives this transport, whether the degradation or transport are associated with sorting or lateral advection, and finally, whether the eDNA arriving at the seafloor is preserved in marine sediments without further distortion of its composition.
Despite the long exposure to degradation under oxic conditions during transport in the water column, and substantially lower concentration of organic matter on the seafloor, there is evidence that planktonic eDNA is preserved in marine sediments and contains exploitable ecological signal. Earlier studies have shown sedaDNA preservation in marine sediments deposited under anoxia with unusually high amounts of organic matter preserved, but later investigations indicate that sedaDNA can also be extracted from normal marine sediments, dominated by clastic or biogenic mineral fractions. In addition, the low temperature of deep-sea water (0–4 °C) ensures a good preservation of sedaDNA. Using planktonic foraminifera as a "Rosetta Stone", allowing benchmarking of sedaDNA signatures by co-occurring fossil tests of these organisms, Morard et al. showed in 2017 that the fingerprint of plankton eDNA arriving on the seafloor preserves the ecological signature of these organisms at a large geographic scale. This indicates that planktonic community eDNA is deposited onto the seafloor below, together with aggregates, skeletons and other sinking planktonic material. If this is true, sedaDNA should be able to record signatures of surface ocean hydrography, affecting the composition of plankton communities, with the same spatial resolution as the skeletal remains of the plankton. In addition, if the plankton eDNA is arriving on the seafloor in association with aggregates or shells, it is possible that it withstands the transport through the water column by fixation onto mineral surfaces. The same mechanism has been proposed to explain the preservation of sedaDNA in sediments, implying that the flux of planktonic eDNA encapsulated in calcite test arriving on the seafloor is conditioned for preservation upon burial.
Planktonic foraminifera sedaDNA is an ideal proxy both “horizontally” to assess the spatial resolution of reconstructing past surface ocean hydrographic features and “vertically”, to unambiguously track the burial of its signal throughout the sediment column. Indeed, the flux of planktonic foraminifera eDNA should be proportionate to the flux of dead foraminiferal shells sinking to the seafloor, allowing independent benchmarking of the eDNA signal. eDNA is a powerful tool to study ecosystem because it does not require direct taxonomic knowledge thus allowing information to be gathered on every organism present in a sample, even at the cryptic level. However, assignment of the eDNA sequences to known organisms is done via comparison with reference sequences (or barcodes) made available in public repositories or curated databases. The taxonomy of planktonic foraminifera is well understood and barcodes exist allowing almost complete mapping of eDNA amplicons on the taxonomy based on foraminiferal test morphology. Importantly, the composition of planktonic foraminifera communities is closely linked to surface hydrography and this signal is preserved by fossil tests deposited on the seafloor. Since foraminiferal eDNA accumulated in the ocean sediment can be recovered, it could be used to analyze changes in planktonic and benthic communities over time.
In 2022, two-million-year-old eDNA genetic material was discovered and sequenced in Greenland, and is currently considered the oldest DNA discovered so far.
== Participatory research and citizen science ==
The relative simplicity of eDNA sampling lends itself to projects which seek to involve local communities in being part of research projects, including collecting and analysing DNA samples. This can empower local communities (including Indigenous peoples) to be actively involved in monitoring the species in an environment, and help make informed decisions as part of participatory action research model. An example of such a project has been demonstrated by the charity Science for All with the 'Wild DNA' project.
== See also ==
Circulating free DNA
Exogenous DNA
Extracellular RNA
RNAs present in environmental samples
Shadow Effect (Genetics)
== References ==
== Further references ==
Schallenberg, Lena; Wood, Susie A.; Pochon, Xavier; Pearman, John K. (2020). "What Can DNA in the Environment Tell Us About an Ecosystem?". Frontiers for Young Minds. 7. doi:10.3389/frym.2019.00150. hdl:2292/50690. S2CID 210714520.
== External links ==
BLAST
Biomeme Guide to eDNA | Wikipedia/Environmental_DNA |
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regulatory RNAs). Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional, such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Regions that are completely nonfunctional are called junk DNA.
== Fraction of non-coding genomic DNA ==
In bacteria, the coding regions typically take up 88% of the genome. The remaining 12% does not encode proteins, but much of it still has biological function through genes where the RNA transcript is functional (non-coding genes) and regulatory sequences, which means that almost all of the bacterial genome has a function. The amount of coding DNA in eukaryotes is usually a much smaller fraction of the genome because eukaryotic genomes contain large amounts of repetitive DNA not found in prokaryotes. The human genome contains somewhere between 1–2% coding DNA. The exact number is not known because there are disputes over the number of functional coding exons and over the total size of the human genome. This means that 98–99% of the human genome consists of non-coding DNA and this includes many functional elements such as non-coding genes and regulatory sequences.
Genome size in eukaryotes can vary over a wide range, even between closely related species. This puzzling observation was originally known as the C-value Paradox where "C" refers to the haploid genome size. The paradox was resolved with the discovery that most of the differences were due to the expansion and contraction of repetitive DNA and not the number of genes. Some researchers speculated that this repetitive DNA was mostly junk DNA. The reasons for the changes in genome size are still being worked out and this problem is called the C-value Enigma.
This led to the observation that the number of genes does not seem to correlate with perceived notions of complexity because the number of genes seems to be relatively constant, an issue termed the G-value Paradox. For example, the genome of the unicellular Polychaos dubium (formerly known as Amoeba dubia) has been reported to contain more than 200 times the amount of DNA in humans (i.e. more than 600 billion pairs of bases vs a bit more than 3 billion in humans). The pufferfish Takifugu rubripes genome is only about one eighth the size of the human genome, yet seems to have a comparable number of genes. Genes take up about 30% of the pufferfish genome and the coding DNA is about 10%. (Non-coding DNA = 90%.) The reduced size of the pufferfish genome is due to a reduction in the length of introns and less repetitive DNA.
Utricularia gibba, a bladderwort plant, has a very small nuclear genome (100.7 Mb) compared to most plants. It likely evolved from an ancestral genome that was 1,500 Mb in size. The bladderwort genome has roughly the same number of genes as other plants but the total amount of coding DNA comes to about 30% of the genome.
The remainder of the genome (70% non-coding DNA) consists of promoters and regulatory sequences that are shorter than those in other plant species. The genes contain introns but there are fewer of them and they are smaller than the introns in other plant genomes. There are noncoding genes, including many copies of ribosomal RNA genes. The genome also contains telomere sequences and centromeres as expected. Much of the repetitive DNA seen in other eukaryotes has been deleted from the bladderwort genome since that lineage split from those of other plants. About 59% of the bladderwort genome consists of transposon-related sequences but since the genome is so much smaller than other genomes, this represents a considerable reduction in the amount of this DNA. The authors of the original 2013 article note that claims of additional functional elements in the non-coding DNA of animals do not seem to apply to plant genomes.
According to a New York Times article, during the evolution of this species, "... genetic junk that didn't serve a purpose was expunged, and the necessary stuff was kept." According to Victor Albert of the University of Buffalo, the plant is able to expunge its so-called junk DNA and "have a perfectly good multicellular plant with lots of different cells, organs, tissue types and flowers, and you can do it without the junk. Junk is not needed."
== Types of non-coding DNA sequences ==
=== Noncoding genes ===
There are two types of genes: protein coding genes and noncoding genes. Noncoding genes are an important part of non-coding DNA and they include genes for transfer RNA and ribosomal RNA. These genes were discovered in the 1960s. Prokaryotic genomes contain genes for a number of other noncoding RNAs but noncoding RNA genes are much more common in eukaryotes.
Typical classes of noncoding genes in eukaryotes include genes for small nuclear RNAs (snRNAs), small nucleolar RNAs (sno RNAs), microRNAs (miRNAs), short interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and long noncoding RNAs (lncRNAs). In addition, there are a number of unique RNA genes that produce catalytic RNAs.
Noncoding genes account for only a few percent of prokaryotic genomes but they can represent a vastly higher fraction in eukaryotic genomes. In humans, the noncoding genes take up at least 6% of the genome, largely because there are hundreds of copies of ribosomal RNA genes. Protein-coding genes occupy about 38% of the genome; a fraction that is much higher than the coding region because genes contain large introns.
The total number of noncoding genes in the human genome is controversial. Some scientists think that there are only about 5,000 noncoding genes while others believe that there may be more than 100,000 (see the article on Non-coding RNA). The difference is largely due to debate over the number of lncRNA genes.
=== Promoters and regulatory elements ===
Promoters are DNA segments near the 5' end of the gene where transcription begins. They are the sites where RNA polymerase binds to initiate RNA synthesis. Every gene has a noncoding promoter.
Regulatory elements are sites that control the transcription of a nearby gene. They are almost always sequences where transcription factors bind to DNA and these transcription factors can either activate transcription (activators) or repress transcription (repressors). Regulatory elements were discovered in the 1960s and their general characteristics were worked out in the 1970s by studying specific transcription factors in bacteria and bacteriophage.
Promoters and regulatory sequences represent an abundant class of noncoding DNA but they mostly consist of a collection of relatively short sequences so they do not take up a very large fraction of the genome. The exact amount of regulatory DNA in mammalian genome is unclear because it is difficult to distinguish between spurious transcription factor binding sites and those that are functional. The binding characteristics of typical DNA-binding proteins were characterized in the 1970s and the biochemical properties of transcription factors predict that in cells with large genomes, the majority of binding sites will not be biologically functional.
Many regulatory sequences occur near promoters, usually upstream of the transcription start site of the gene. Some occur within a gene and a few are located downstream of the transcription termination site. In eukaryotes, there are some regulatory sequences that are located at a considerable distance from the promoter region. These distant regulatory sequences are often called enhancers but there is no rigorous definition of enhancer that distinguishes it from other transcription factor binding sites.
=== Introns ===
Introns are the parts of a gene that are transcribed into the precursor RNA sequence, but ultimately removed by RNA splicing during the processing to mature RNA. Introns are found in both types of genes: protein-coding genes and noncoding genes. They are present in prokaryotes but they are much more common in eukaryotic genomes.
Group I and group II introns take up only a small percentage of the genome when they are present. Spliceosomal introns (see Figure) are only found in eukaryotes and they can represent a substantial proportion of the genome. In humans, for example, introns in protein-coding genes cover 37% of the genome. Combining that with about 1% coding sequences means that protein-coding genes occupy about 38% of the human genome. The calculations for noncoding genes are more complicated because there is considerable dispute over the total number of noncoding genes but taking only the well-defined examples means that noncoding genes occupy at least 6% of the genome.
=== Untranslated regions ===
The standard biochemistry and molecular biology textbooks describe non-coding nucleotides in mRNA located between the 5' end of the gene and the translation initiation codon. These regions are called 5'-untranslated regions or 5'-UTRs. Similar regions called 3'-untranslated regions (3'-UTRs) are found at the end of the gene. The 5'-UTRs and 3'UTRs are very short in bacteria but they can be several hundred nucleotides in length in eukaryotes. They contain short elements that control the initiation of translation (5'-UTRs) and transcription termination (3'-UTRs) as well as regulatory elements that may control mRNA stability, processing, and targeting to different regions of the cell.
=== Origins of replication ===
DNA synthesis begins at specific sites called origins of replication. These are regions of the genome where the DNA replication machinery is assembled and the DNA is unwound to begin DNA synthesis. In most cases, replication proceeds in both directions from the replication origin.
The main features of replication origins are sequences where specific initiation proteins are bound. A typical replication origin covers about 100-200 base pairs of DNA. Prokaryotes have one origin of replication per chromosome or plasmid but there are usually multiple origins in eukaryotic chromosomes. The human genome contains about 100,000 origins of replication representing about 0.3% of the genome.
=== Centromeres ===
Centromeres are the sites where spindle fibers attach to newly replicated chromosomes in order to segregate them into daughter cells when the cell divides. Each eukaryotic chromosome has a single functional centromere that is seen as a constricted region in a condensed metaphase chromosome. Centromeric DNA consists of a number of repetitive DNA sequences that often take up a significant fraction of the genome because each centromere can be millions of base pairs in length. In humans, for example, the sequences of all 24 centromeres have been determined and they account for about 6% of the genome. However, it is unlikely that all of this noncoding DNA is essential since there is considerable variation in the total amount of centromeric DNA in different individuals. Centromeres are another example of functional noncoding DNA sequences that have been known for almost half a century and it is likely that they are more abundant than coding DNA.
=== Telomeres ===
Telomeres are regions of repetitive DNA at the end of a chromosome, which provide protection from chromosomal deterioration during DNA replication. Recent studies have shown that telomeres function to aid in its own stability. Telomeric repeat-containing RNA (TERRA) are transcripts derived from telomeres. TERRA has been shown to maintain telomerase activity and lengthen the ends of chromosomes.
=== Scaffold attachment regions ===
Both prokaryotic and eukarotic genomes are organized into large loops of protein-bound DNA. In eukaryotes, the bases of the loops are called scaffold attachment regions (SARs) and they consist of stretches of DNA that bind an RNA/protein complex to stabilize the loop. There are about 100,000 loops in the human genome and each SAR consists of about 100 bp of DNA, so the total amount of DNA devoted to SARs accounts for about 0.3% of the human genome.
=== Pseudogenes ===
Pseudogenes are mostly former genes that have become non-functional due to mutation, but the term also refers to inactive DNA sequences that are derived from RNAs produced by functional genes (processed pseudogenes). Pseudogenes are only a small fraction of noncoding DNA in prokaryotic genomes because they are eliminated by negative selection. In some eukaryotes, however, pseudogenes can accumulate because selection is not powerful enough to eliminate them (see Nearly neutral theory of molecular evolution).
The human genome contains about 15,000 pseudogenes derived from protein-coding genes and an unknown number derived from noncoding genes. They may cover a substantial fraction of the genome (~5%) since many of them contain former intron sequences.
Pseudogenes are junk DNA by definition and they evolve at the neutral rate as expected for junk DNA. Some former pseudogenes have secondarily acquired a function and this leads some scientists to speculate that most pseudogenes are not junk because they have a yet-to-be-discovered function.
=== Repeat sequences, transposons and viral elements ===
Transposons and retrotransposons are mobile genetic elements. Retrotransposon repeated sequences, which include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), account for a large proportion of the genomic sequences in many species. Alu sequences, classified as a short interspersed nuclear element, are the most abundant mobile elements in the human genome. Some examples have been found of SINEs exerting transcriptional control of some protein-encoding genes.
Endogenous retrovirus sequences are the product of reverse transcription of retrovirus genomes into the genomes of germ cells. Mutation within these retro-transcribed sequences can inactivate the viral genome.
Over 8% of the human genome is made up of (mostly decayed) endogenous retrovirus sequences, as part of the over 42% fraction that is recognizably derived of retrotransposons, while another 3% can be identified to be the remains of DNA transposons. Much of the remaining half of the genome that is currently without an explained origin is expected to have found its origin in transposable elements that were active so long ago (> 200 million years) that random mutations have rendered them unrecognizable. Genome size variation in at least two kinds of plants is mostly the result of retrotransposon sequences.
=== Highly repetitive DNA ===
Highly repetitive DNA consists of short stretches of DNA that are repeated many times in tandem (one after the other). The repeat segments are usually between 2 bp and 10 bp but longer ones are known. Highly repetitive DNA is rare in prokaryotes but common in eukaryotes, especially those with large genomes. It is sometimes called satellite DNA.
Most of the highly repetitive DNA is found in centromeres and telomeres (see above) and most of it is functional although some might be redundant. The other significant fraction resides in short tandem repeats (STRs; also called microsatellites) consisting of short stretches of a simple repeat such as ATC. There are about 350,000 STRs in the human genome and they are scattered throughout the genome with an average length of about 25 repeats.
Variations in the number of STR repeats can cause genetic diseases when they lie within a gene but most of these regions appear to be non-functional junk DNA where the number of repeats can vary considerably from individual to individual. This is why these length differences are used extensively in DNA fingerprinting.
=== Junk DNA ===
Junk DNA is DNA that has no biologically relevant function such as pseudogenes and fragments of once active transposons. Bacteria and viral genomes have very little junk DNA but some eukaryotic genomes may have a substantial amount of junk DNA. The exact amount of nonfunctional DNA in humans and other species with large genomes has not been determined and there is considerable controversy in the scientific literature.
The nonfunctional DNA in bacterial genomes is mostly located in the intergenic fraction of non-coding DNA but in eukaryotic genomes it may also be found within introns. There are many examples of functional DNA elements in non-coding DNA, and it is erroneous to equate non-coding DNA with junk DNA.
== Genome-wide association studies (GWAS) and non-coding DNA ==
Genome-wide association studies (GWAS) identify linkages between alleles and observable traits such as phenotypes and diseases. Most of the associations are between single-nucleotide polymorphisms (SNPs) and the trait being examined and most of these SNPs are located in non-functional DNA. The association establishes a linkage that helps map the DNA region responsible for the trait but it does not necessarily identify the mutations causing the disease or phenotypic difference.
SNPs that are tightly linked to traits are the ones most likely to identify a causal mutation. (The association is referred to as tight linkage disequilibrium.) About 12% of these polymorphisms are found in coding regions; about 40% are located in introns; and most of the rest are found in intergenic regions, including regulatory sequences.
== See also ==
Conserved non-coding sequence
Eukaryotic chromosome fine structure
Gene-centered view of evolution
Gene regulatory network
Intergenic region
Intragenomic conflict
Phylogenetic footprinting
Transcriptome
Non-coding RNA
Gene desert
The Onion Test
== References ==
== Further reading ==
== External links ==
Plant DNA C-values Database at Royal Botanic Gardens, Kew
Fungal Genome Size Database at Estonian Institute of Zoology and Botany
ENCODE: The human encyclopaedia at Nature ENCODE | Wikipedia/Non-coding_DNA |
Protein A is a 42 kDa surface protein originally found in the cell wall of the bacteria Staphylococcus aureus. It is encoded by the spa gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical research because of its ability to bind immunoglobulins. It is composed of five homologous Ig-binding domains that fold into a three-helix bundle. Each domain is able to bind proteins from many mammalian species, most notably IgGs. It binds the heavy chain within the Fc region of most immunoglobulins and also within the Fab region in the case of the human VH3 family. Through these interactions in serum, where IgG molecules are bound in the wrong orientation (in relation to normal antibody function), the bacteria disrupts opsonization and phagocytosis.
== History ==
As a by-product of his work on type-specific staphylococcus antigens, Verwey reported in
1940 that a protein fraction prepared from extracts of these bacteria non-specifically precipitated rabbit antisera raised against different staphylococcus types. In 1958, Jensen confirmed Verwey's finding and showed that rabbit pre-immunization sera as well as normal human sera bound to the active component in the staphylococcus extract; he designated this component Antigen A (because it was found in fraction A of the extract) but thought it was a polysaccharide. The misclassification of the protein was the result of faulty tests, but it was not long thereafter (1962) that Löfkvist and Sjöquist corrected the error and confirmed that Antigen A was in fact a surface protein on the bacterial wall of certain strains of S. aureus. The Bergen group from Norway named the protein "Protein A" after the antigen fraction isolated by Jensen.
== Protein A antibody binding ==
It has been shown via crystallographic refinement that the primary binding site for protein A is on the Fc region, between the CH2 and CH3 domains. In addition, protein A has been shown to bind human IgG molecules containing IgG F(ab')2 fragments from the human VH3 gene family.
Protein A can bind with strong affinity to the Fc portion of immunoglobulin of certain species as shown in the below table.
== Other antibody binding proteins ==
In addition to protein A, other immunoglobulin-binding bacterial proteins such as protein G, protein A/G and protein L are all commonly used to purify, immobilize or detect immunoglobulins.
== Role in pathogenesis ==
As a pathogen, Staphylococcus aureus utilizes protein A, along with a host of other proteins and surface factors, to aid its survival and virulence. To this end, protein A plays a multifaceted role:
By binding the Fc portion of antibodies, protein A renders them inaccessible to the opsonins, thus impairing phagocytosis of the bacteria via immune cell attack.
Protein A facilitates the adherence of S. aureus to human von Willebrand factor (vWF)-coated surfaces, thus increasing the bacteria's infectiousness at the site of skin penetration.
Protein A can inflame lung tissue by binding to tumor necrosis factor 1 (TNFR-1) receptors. This interaction has been shown to play a key role in the pathogenesis of staphylococcal pneumonia.
Protein A has been shown to cripple humoral (antibody-mediated) immunity which in turn means that individuals can be repeatedly infected with S. aureus since they cannot mount a strong antibody response.
Protein A has been shown to promote the formation of biofilms both when the protein is covalently linked to the bacterial cell wall as well as in solution.
Protein A helps inhibit phagocytic engulfment and acts as an immunological disguise. Higher levels of protein A in different strains of S. aureus have been associated with nasal carriage of this bacteria.
Mutants of S. aureus lacking protein A are more efficiently phagocytosed in vitro, and mutants in infection models have diminished virulence.
== Production ==
Protein A is produced and purified in industrial fermentation for use in immunology, biological research and industrial applications (see below). Natural (or native) protein A can be cultured in Staphylococcus aureus and contains the five homologous antibody binding regions described above and a C-terminal region for cell wall attachment. Today, protein A is more commonly produced recombinantly in Escherichia coli. (Brevibacillus has also been shown to be an effective host.) Recombinant versions of protein A also contain the five homologous antibody binding domains but may vary in other parts of the structure in order to facilitate coupling to porous substrates. Engineered versions of the protein are also available, the first of which was rProtein A, B4, C-CYS. Engineered versions are multimers (typically tetramers, pentamers or hexamers) of a single domain which has been modified to improve usability in industrial applications.
== Research ==
Protein A is often coupled to other molecules such as a fluorescent dye, enzymes, biotin, colloidal gold or radioactive iodine without affecting the antibody binding site. Examples including protein A–gold (PAG) stain is used in immunogold labelling, fluorophore coupled protein A for immunofluorescence, and DNA docking strand coupled protein A for DNA-PAINT imaging. It is also widely utilized coupled to magnetic, latex and agarose beads.
Protein A is often immobilized onto a solid support and used as reliable method for purifying total IgG from crude protein mixtures such as serum or ascites fluid, or coupled with one of the above markers to detect the presence of antibodies. The first example of protein A being coupled to a porous bead for purification of IgG was published in 1972. Immunoprecipitation studies with protein A conjugated to beads are also commonly used to purify proteins or protein complexes indirectly through antibodies against the protein or protein complex of interest.
== Role in industrial purification of antibodies ==
The first reference in the literature to a commercially available protein A chromatography resin appeared in 1976. Today, chromatographic separation using protein A immobilized on porous substrates is the most widely established method for purifying monoclonal antibodies (mAbs) from harvest cell culture supernatant. The choice of protein A as the preferred method is due to the high purity and yield which are easily and reliably achieved. This forms the basis for a general antibody purification "platform" which simplifies manufacturing operations and reduces the time and effort required to develop purification processes. A typical mAb purification process is shown at right. Albeit the long history of protein A chromatography for the production of antibodies, the process is still being improved today. Continuous chromatography, more precisely periodic counter-current chromatography, enormously increases the productivity of the purification step.
== References == | Wikipedia/Protein_A |
In genetics, complementary DNA (cDNA) is DNA that was reverse transcribed (via reverse transcriptase) from an RNA (e.g., messenger RNA or microRNA). cDNA exists in both single-stranded and double-stranded forms and in both natural and engineered forms.
In engineered forms, it often is a copy (replicate) of the naturally occurring DNA from any particular organism's natural genome; the organism's own mRNA was naturally transcribed from its DNA, and the cDNA is reverse transcribed from the mRNA, yielding a duplicate of the original DNA. Engineered cDNA is often used to express a specific protein in a cell that does not normally express that protein (i.e., heterologous expression), or to sequence or quantify mRNA molecules using DNA based methods (qPCR, RNA-seq). cDNA that codes for a specific protein can be transferred to a recipient cell for expression as part of recombinant DNA, often bacterial or yeast expression systems. cDNA is also generated to analyze transcriptomic profiles in bulk tissue, single cells, or single nuclei in assays such as microarrays, qPCR, and RNA-seq.
In natural forms, cDNA is produced by retroviruses (such as HIV-1, HIV-2, simian immunodeficiency virus, etc.) and then integrated into the host's genome, where it creates a provirus.
The term cDNA is also used, typically in a bioinformatics context, to refer to an mRNA transcript's sequence, expressed as DNA bases (deoxy-GCAT) rather than RNA bases (GCAU).
Patentability of cDNA was a subject of a 2013 US Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. As a compromise, the Court declared, that exons-only cDNA is patent-eligible, whereas isolated sequences of naturally occurring DNA comprising introns are not.
== Synthesis ==
RNA serves as a template for cDNA synthesis. In cellular life, cDNA is generated by viruses and retrotransposons for integration of RNA into target genomic DNA. In molecular biology, RNA is purified from source material after genomic DNA, proteins and other cellular components are removed. cDNA is then synthesized through in vitro reverse transcription.
=== RNA purification ===
RNA is transcribed from genomic DNA in host cells and is extracted by first lysing cells then purifying RNA utilizing widely used methods such as phenol-chloroform, silica column, and bead-based RNA extraction methods. Extraction methods vary depending on the source material. For example, extracting RNA from plant tissue requires additional reagents, such as polyvinylpyrrolidone (PVP), to remove phenolic compounds, carbohydrates, and other compounds that will otherwise render RNA unusable. To remove DNA and proteins, enzymes such as DNase and Proteinase K are used for degradation. Importantly, RNA integrity is maintained by inactivating RNases with chaotropic agents such as guanidinium isothiocyanate, sodium dodecyl sulphate (SDS), phenol or chloroform. Total RNA is then separated from other cellular components and precipitated with alcohol. Various commercial kits exist for simple and rapid RNA extractions for specific applications. Additional bead-based methods can be used to isolate specific sub-types of RNA (e.g. mRNA and microRNA) based on size or unique RNA regions.
=== Reverse transcription ===
==== First-strand synthesis ====
Using a reverse transcriptase enzyme and purified RNA templates, one strand of cDNA is produced (first-strand cDNA synthesis). The M-MLV reverse transcriptase from the Moloney murine leukemia virus is commonly used due to its reduced RNase H activity suited for transcription of longer RNAs. The AMV reverse transcriptase from the avian myeloblastosis virus may also be used for RNA templates with strong secondary structures (i.e. high melting temperature). cDNA is commonly generated from mRNA for gene expression analyses such as RT-qPCR and RNA-seq. mRNA is selectively reverse transcribed using oligo-dT primers that are the reverse complement of the poly-adenylated tail on the 3' end of all mRNA. The oligo-dT primer anneals to the poly-adenylated tail of the mRNA to serve as a binding site for the reverse transcriptase to begin reverse transcription. An optimized mixture of oligo-dT and random hexamer primers increases the chance of obtaining full-length cDNA while reducing 5' or 3' bias. Ribosomal RNA may also be depleted to enrich both mRNA and non-poly-adenylated transcripts such as some non-coding RNA.
==== Second-strand synthesis ====
The result of first-strand syntheses, RNA-DNA hybrids, can be processed through multiple second-strand synthesis methods or processed directly in downstream assays. An early method known as hairpin-primed synthesis relied on hairpin formation on the 3' end of the first-strand cDNA to prime second-strand synthesis. However, priming is random and hairpin hydrolysis leads to loss of information. The Gubler and Hoffman Procedure uses E. Coli RNase H to nick mRNA that is replaced with E. Coli DNA Polymerase I and sealed with E. Coli DNA Ligase. An optimization of this procedure relies on low RNase H activity of M-MLV to nick mRNA with remaining RNA later removed by adding RNase H after DNA Polymerase translation of the second-strand cDNA. This prevents lost sequence information at the 5' end of the mRNA.
== Applications ==
Complementary DNA is often used in gene cloning or as gene probes or in the creation of a cDNA library. When scientists transfer a gene from one cell into another cell in order to express the new genetic material as a protein in the recipient cell, the cDNA will be added to the recipient (rather than the entire gene), because the DNA for an entire gene may include DNA that does not code for the protein or that interrupts the coding sequence of the protein (e.g., introns). Partial sequences of cDNAs are often obtained as expressed sequence tags.
With amplification of DNA sequences via polymerase chain reaction (PCR) now commonplace, one will typically conduct reverse transcription as an initial step, followed by PCR to obtain an exact sequence of cDNA for intra-cellular expression. This is achieved by designing sequence-specific DNA primers that hybridize to the 5' and 3' ends of a cDNA region coding for a protein. Once amplified, the sequence can be cut at each end with nucleases and inserted into one of many small circular DNA sequences known as expression vectors. Such vectors allow for self-replication, inside the cells, and potentially integration in the host DNA. They typically also contain a strong promoter to drive transcription of the target cDNA into mRNA, which is then translated into protein.
cDNA is also used to study gene expression via methods such as RNA-seq or RT-qPCR. For sequencing, RNA must be fragmented due to sequencing platform size limitations. Additionally, second-strand synthesized cDNA must be ligated with adapters that allow cDNA fragments to be PCR amplified and bind to sequencing flow cells. Gene-specific analysis methods commonly use microarrays and RT-qPCR to quantify cDNA levels via fluorometric and other methods.
On 13 June 2013, the United States Supreme Court ruled in the case of Association for Molecular Pathology v. Myriad Genetics that while naturally occurring genes cannot be patented, cDNA is patent-eligible because it does not occur naturally.
== Viruses and retrotransposons ==
Some viruses also use cDNA to turn their viral RNA into mRNA (viral RNA → cDNA → mRNA). The mRNA is used to make viral proteins to take over the host cell.
An example of this first step from viral RNA to cDNA can be seen in the HIV cycle of infection. Here, the host cell membrane becomes attached to the virus' lipid envelope which allows the viral capsid with two copies of viral genome RNA to enter the host. The cDNA copy is then made through reverse transcription of the viral RNA, a process facilitated by the chaperone CypA and a viral capsid associated reverse transcriptase.
cDNA is also generated by retrotransposons in eukaryotic genomes. Retrotransposons are mobile genetic elements that move themselves within, and sometimes between, genomes via RNA intermediates. This mechanism is shared with viruses with the exclusion of the generation of infectious particles.
== See also ==
cDNA library – Type of DNA library
cDNA microarray – Collection of microscopic DNA spots attached to a solid surfacePages displaying short descriptions of redirect targets
RNA-Seq – Lab technique in cellular biology
Real-time polymerase chain reaction – Laboratory technique of molecular biology (RT-qPCR)
== References ==
Mark D. Adams et al. "Complementary DNA Sequencing: Expressed Sequence Tags and Human Genome Project." Science (American Association for the Advancement of Science) 252.5013 (1991): 1651–1656. Web.
Philip M. Murphy, and H. Lee Tiffany. "Cloning of Complementary DNA Encoding a Functional Human Interleukin-8 Receptor." Science (American Association for the Advancement of Science) 253.5025 (1991): 1280–1283. Web.
== External links ==
H-Invitational Database
Functional Annotation of the Mouse database
Complementary DNA tool
http://news.icecric.com/today-match-prediction/ | Wikipedia/Complementary_DNA |
Nucleic acid thermodynamics is the study of how temperature affects the nucleic acid structure of double-stranded DNA (dsDNA). The melting temperature (Tm) is defined as the temperature at which half of the DNA strands are in the random coil or single-stranded (ssDNA) state. Tm depends on the length of the DNA molecule and its specific nucleotide sequence. DNA, when in a state where its two strands are dissociated (i.e., the dsDNA molecule exists as two independent strands), is referred to as having been denatured by the high temperature.
== Concepts ==
=== Hybridization ===
Hybridization is the process of establishing a non-covalent, sequence-specific interaction between two or more complementary strands of nucleic acids into a single complex, which in the case of two strands is referred to as a duplex. Oligonucleotides, DNA, or RNA will bind to their complement under normal conditions, so two perfectly complementary strands will bind to each other readily. In order to reduce the diversity and obtain the most energetically preferred complexes, a technique called annealing is used in laboratory practice. However, due to the different molecular geometries of the nucleotides, a single inconsistency between the two strands will make binding between them less energetically favorable. Measuring the effects of base incompatibility by quantifying the temperature at which two strands anneal can provide information as to the similarity in base sequence between the two strands being annealed. The complexes may be dissociated by thermal denaturation, also referred to as melting. In the absence of external negative factors, the processes of hybridization and melting may be repeated in succession indefinitely, which lays the ground for polymerase chain reaction. Most commonly, the pairs of nucleic bases A=T and G≡C are formed, of which the latter is more stable.
=== Denaturation ===
DNA denaturation, also called DNA melting, is the process by which double-stranded deoxyribonucleic acid unwinds and separates into single-stranded strands through the breaking of hydrophobic stacking attractions between the bases. See Hydrophobic effect. Both terms are used to refer to the process as it occurs when a mixture is heated, although "denaturation" can also refer to the separation of DNA strands induced by chemicals like formamide or urea.
The process of DNA denaturation can be used to analyze some aspects of DNA. Because cytosine / guanine base-pairing is generally stronger than adenine / thymine base-pairing, the amount of cytosine and guanine in a genome is called its GC-content and can be estimated by measuring the temperature at which the genomic DNA melts. Higher temperatures are associated with high GC content.
DNA denaturation can also be used to detect sequence differences between two different DNA sequences. DNA is heated and denatured into single-stranded state, and the mixture is cooled to allow strands to rehybridize. Hybrid molecules are formed between similar sequences and any differences between those sequences will result in a disruption of the base-pairing. On a genomic scale, the method has been used by researchers to estimate the genetic distance between two species, a process known as DNA-DNA hybridization. In the context of a single isolated region of DNA, denaturing gradient gels and temperature gradient gels can be used to detect the presence of small mismatches between two sequences, a process known as temperature gradient gel electrophoresis.
Methods of DNA analysis based on melting temperature have the disadvantage of being proxies for studying the underlying sequence; DNA sequencing is generally considered a more accurate method.
The process of DNA melting is also used in molecular biology techniques, notably in the polymerase chain reaction. Although the temperature of DNA melting is not diagnostic in the technique, methods for estimating Tm are important for determining the appropriate temperatures to use in a protocol. DNA melting temperatures can also be used as a proxy for equalizing the hybridization strengths of a set of molecules, e.g. the oligonucleotide probes of DNA microarrays.
=== Annealing ===
Annealing, in genetics, means for complementary sequences of single-stranded DNA or RNA to pair by hydrogen bonds to form a double-stranded polynucleotide. Before annealing can occur, one of the strands may need to be phosphorylated by an enzyme such as kinase to allow proper hydrogen bonding to occur. The term annealing is often used to describe the binding of a DNA probe, or the binding of a primer to a DNA strand during a polymerase chain reaction. The term is also often used to describe the reformation (renaturation) of reverse-complementary strands that were separated by heat (thermally denatured). Proteins such as RAD52 can help DNA anneal. DNA strand annealing is a key step in pathways of homologous recombination. In particular, during meiosis, synthesis-dependent strand annealing is a major pathway of homologous recombination.
=== Stacking ===
Stacking is the stabilizing interaction between the flat surfaces of adjacent bases. Stacking can happen with any face of the base, that is 5'-5', 3'-3', and vice versa.
Stacking in "free" nucleic acid molecules is mainly contributed by intermolecular force, specifically electrostatic attraction among aromatic rings, a process also known as pi stacking. For biological systems with water as a solvent, hydrophobic effect contributes and helps in formation of a helix. Stacking is the main stabilizing factor in the DNA double helix.
Contribution of stacking to the free energy of the molecule can be experimentally estimated by observing the bent-stacked equilibrium in nicked DNA. Such stabilization is dependent on the sequence. The extent of the stabilization varies with salt concentrations and temperature.
== Thermodynamics of the two-state model ==
Several formulas are used to calculate Tm values. Some formulas are more accurate in predicting melting temperatures of DNA duplexes. For DNA oligonucleotides, i.e. short sequences of DNA, the thermodynamics of hybridization can be accurately described as a two-state process. In this approximation one neglects the possibility of intermediate partial binding states in the formation of a double strand state from two single stranded oligonucleotides. Under this assumption one can elegantly describe the thermodynamic parameters for forming double-stranded nucleic acid AB from single-stranded nucleic acids A and B.
AB ↔ A + B
The equilibrium constant for this reaction is
K
=
[
A
]
[
B
]
[
A
B
]
{\displaystyle K={\frac {[A][B]}{[AB]}}}
. According to the Van´t Hoff equation, the relation between free energy, ΔG, and K is ΔG° = -RTln K, where R is the ideal gas law constant, and T is the kelvin temperature of the reaction. This gives, for the nucleic acid system,
Δ
G
∘
=
−
R
T
ln
[
A
]
[
B
]
[
A
B
]
{\displaystyle \Delta G^{\circ }=-RT\ln {\frac {[A][B]}{[AB]}}}
.
The melting temperature, Tm, occurs when half of the double-stranded nucleic acid has dissociated. If no additional nucleic acids are present, then [A], [B], and [AB] will be equal, and equal to half the initial concentration of double-stranded nucleic acid, [AB]initial. This gives an expression for the melting point of a nucleic acid duplex of
T
m
=
−
Δ
G
∘
R
ln
[
A
B
]
i
n
i
t
i
a
l
2
{\displaystyle T_{m}=-{\frac {\Delta G^{\circ }}{R\ln {\frac {[AB]_{initial}}{2}}}}}
.
Because ΔG° = ΔH° -TΔS°, Tm is also given by
T
m
=
Δ
H
∘
Δ
S
∘
−
R
ln
[
A
B
]
i
n
i
t
i
a
l
2
{\displaystyle T_{m}={\frac {\Delta H^{\circ }}{\Delta S^{\circ }-R\ln {\frac {[AB]_{initial}}{2}}}}}
.
The terms ΔH° and ΔS° are usually given for the association and not the dissociation reaction (see the nearest-neighbor method for example). This formula then turns into:
T
m
=
Δ
H
∘
Δ
S
∘
+
R
ln
(
[
A
]
t
o
t
a
l
−
[
B
]
t
o
t
a
l
/
2
)
{\displaystyle T_{m}={\frac {\Delta H^{\circ }}{\Delta S^{\circ }+R\ln([A]_{total}-[B]_{total}/2)}}}
, where [B]total ≤ [A]total.
As mentioned, this equation is based on the assumption that only two states are involved in melting: the double stranded state and the random-coil state. However, nucleic acids may melt via several intermediate states. To account for such complicated behavior, the methods of statistical mechanics must be used, which is especially relevant for long sequences.
== Estimating thermodynamic properties from nucleic acid sequence ==
The previous paragraph shows how melting temperature and thermodynamic parameters (ΔG° or ΔH° & ΔS°) are related to each other. From the observation of melting temperatures one can experimentally determine the thermodynamic parameters. Vice versa, and important for applications, when the thermodynamic parameters of a given nucleic acid sequence are known, the melting temperature can be predicted. It turns out that for oligonucleotides, these parameters can be well approximated by the nearest-neighbor model.
=== Nearest-neighbor method ===
The interaction between bases on different strands depends somewhat on the neighboring bases. Instead of treating a DNA helix as a string of interactions between base pairs, the nearest-neighbor model treats a DNA helix as a string of interactions between 'neighboring' base pairs. So, for example, the DNA shown below has nearest-neighbor interactions indicated by the arrows.
↓ ↓ ↓ ↓ ↓
5' C-G-T-T-G-A 3'
3' G-C-A-A-C-T 5'
The free energy of forming this DNA from the individual strands, ΔG°, is represented (at 37 °C) as
ΔG°37(predicted) = ΔG°37(C/G initiation) + ΔG°37(CG/GC) + ΔG°37(GT/CA) + ΔG°37(TT/AA) + ΔG°37(TG/AC) + ΔG°37(GA/CT) + ΔG°37(A/T initiation)
Except for the C/G initiation term, the first term represents the free energy of the first base pair, CG, in the absence of a nearest neighbor. The second term includes both the free energy of formation of the second base pair, GC, and stacking interaction between this base pair and the previous base pair. The remaining terms are similarly defined. In general, the free energy of forming a nucleic acid duplex is
Δ
G
37
∘
(
t
o
t
a
l
)
=
Δ
G
37
∘
(
i
n
i
t
i
a
t
i
o
n
s
)
+
∑
i
=
1
10
n
i
Δ
G
37
∘
(
i
)
{\displaystyle \Delta G_{37}^{\circ }(\mathrm {total} )=\Delta G_{37}^{\circ }(\mathrm {initiations} )+\sum _{i=1}^{10}n_{i}\Delta G_{37}^{\circ }(i)}
,
where
Δ
G
37
∘
(
i
)
{\displaystyle \Delta G_{37}^{\circ }(i)}
represents the free energy associated with one of the ten possible the nearest-neighbor nucleotide pairs, and
n
i
{\displaystyle n_{i}}
represents its count in the sequence.
Each ΔG° term has enthalpic, ΔH°, and entropic, ΔS°, parameters, so the change in free energy is also given by
Δ
G
∘
(
t
o
t
a
l
)
=
Δ
H
t
o
t
a
l
∘
−
T
Δ
S
t
o
t
a
l
∘
{\displaystyle \Delta G^{\circ }(\mathrm {total} )=\Delta H_{\mathrm {total} }^{\circ }-T\Delta S_{\mathrm {total} }^{\circ }}
.
Values of ΔH° and ΔS° have been determined for the ten possible pairs of interactions. These are given in Table 1, along with the value of ΔG° calculated at 37 °C. Using these values, the value of ΔG37° for the DNA duplex shown above is calculated to be −22.4 kJ/mol. The experimental value is −21.8 kJ/mol.
The parameters associated with the ten groups of neighbors shown in table 1 are determined from melting points of short oligonucleotide duplexes. It works out that only eight of the ten groups are independent.
The nearest-neighbor model can be extended beyond the Watson-Crick pairs to include parameters for interactions between mismatches and neighboring base pairs. This allows the estimation of the thermodynamic parameters of sequences containing isolated mismatches, like e.g. (arrows indicating mismatch)
↓↓↓
5' G-G-A-C-T-G-A-C-G 3'
3' C-C-T-G-G-C-T-G-C 5'
These parameters have been fitted from melting experiments and an extension of Table 1 which includes mismatches can be found in literature.
A more realistic way of modeling the behavior of nucleic acids would seem to be to have parameters that depend on the neighboring groups on both sides of a nucleotide, giving a table with entries like "TCG/AGC". However, this would involve around 32 groups for Watson-Crick pairing and even more for sequences containing mismatches; the number of DNA melting experiments needed to get reliable data for so many groups would be inconveniently high. However, other means exist to access thermodynamic parameters of nucleic acids: microarray technology allows hybridization monitoring of tens of thousands sequences in parallel. This data, in combination with molecular adsorption theory allows the determination of many thermodynamic parameters in a single experiment and to go beyond the nearest neighbor model. In general the predictions from the nearest neighbor method agree reasonably well with experimental results, but some unexpected outlying sequences, calling for further insights, do exist. Finally, we should also mention the increased accuracy provided by single molecule unzipping assays which provide a wealth of new insight into the thermodynamics of DNA hybridization and the validity of the nearest-neighbour model as well.
== See also ==
Melting point
Primer (molecular biology) for calculations of Tm
Base pair
Complementary DNA
Western blot
== References ==
== External links ==
Tm calculations in OligoAnalyzer – Integrated DNA Technologies
DNA thermodynamics calculations – Tm, melting profile, mismatches, free energy calculations
Tm calculation – by bioPHP.org.
https://web.archive.org/web/20080516194508/http://www.promega.com/biomath/calc11.htm#disc
Invitrogen Tm calculation
AnnHyb Open Source software for Tm calculation using the Nearest-neighbour method
Sigma-aldrich technical notes
Primer3 calculation
"Discovery of the Hybrid Helix and the First DNA-RNA Hybridization" by Alexander Rich
uMelt: Melting Curve Prediction
Tm Tool
Nearest Neighbor Database: Provides a description of RNA-RNA interaction nearest neighbor parameters and examples of their use. | Wikipedia/DNA_melting |
Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. It adheres to Mendelian inheritance, with information coming from two parents, one male and one female—rather than matrilineally (through the mother) as in mitochondrial DNA.
== Structure ==
Nuclear DNA is a nucleic acid, a polymeric biomolecule or biopolymer, found in the nucleus of eukaryotic cells. Its structure is a double helix, with two strands wound around each other, a structure first described by Francis Crick and James D. Watson (1953) using data collected by Rosalind Franklin. Each strand is a long polymer chain of repeating nucleotides. Each nucleotide is composed of a five-carbon sugar, a phosphate group, and an organic base. Nucleotides are distinguished by their bases: purines, large bases that include adenine and guanine; and pyrimidines, small bases that include thymine and cytosine. Chargaff's rules state that adenine always pairs with thymine, and guanine always with cytosine. The phosphate groups are held together by a phosphodiester bond and the bases are held together by hydrogen bonds.
== Differences to mitochondrial DNA ==
Nuclear DNA and mitochondrial DNA differ in many ways, starting with location and structure. Nuclear DNA is located within the nucleus of eukaryote cells and usually has two copies per cell while mitochondrial DNA is located in the mitochondria and contains 100–1,000 copies per cell. The structure of nuclear DNA chromosomes is linear with open ends and includes 46 chromosomes and contains for example 3 billion nucleotides in humans while the structure of Mitochondrial DNA chromosome is usually closed, circular, and contains for example 16,569 nucleotides in humans. Nuclear DNA in animals is diploid, ordinarily inheriting the DNA from two parents, while mitochondrial DNA is haploid, coming only from the mother. The mutation rate for nuclear DNA is less than 0.3% while that of mitochondrial DNA is generally higher.
== Forensics ==
Nuclear DNA is known as the molecule of life and contains the genetic instructions for the development of all eukaryotic organisms. It is found in almost every cell in the human body, with exceptions such as red blood cells. Everyone has a unique genetic blueprint, even identical twins. Forensic departments such as the Bureau of Criminal Apprehension (BCA) and Federal Bureau of Investigation (FBI) are able to use techniques involving nuclear DNA to compare samples in a case. Techniques used include polymerase chain reaction (PCR), which allows one to utilize very small amounts of DNA by making copies of targeted regions on the molecule, also known as short tandem repeats (STRs).
== Cell division ==
Like mitosis, meiosis is a form of eukaryotic cell division. Meiosis gives rise to four unique daughter cells, each of which has half the number of chromosomes as the parent cell. Because meiosis creates cells that are destined to become gametes (or reproductive cells), this reduction in chromosome number is critical — without it, the union of two gametes during fertilization would result in offspring with twice the normal number of chromosomes.
Meiosis creates new combinations of genetic material in each of the four daughter cells. These new combinations result from the exchange of DNA between paired chromosomes. Such an exchange means that the gametes produced through meiosis often exhibit considerable genetic variation.
Meiosis involves two rounds of nuclear division, not just one. Prior to undergoing meiosis, a cell goes through an interphase period in which it grows, replicates its chromosomes, and checks all of its systems to ensure that it is ready to divide.
Like mitosis, meiosis also has distinct stages called prophase, metaphase, anaphase, and telophase. A key difference, however, is that during meiosis, each of these phases occurs twice — once during the first round of division, called meiosis I, and again during the second round of division, called meiosis II.
== Replication ==
Prior to cell division, the DNA material in the original cell must be duplicated so that after cell division, each new cell contains the full amount of DNA material. The process of DNA duplication is usually called replication. The replication is termed semiconservative since each new cell contains one strand of original DNA and one newly synthesized strand of DNA. The original polynucleotide strand of DNA serves as a template to guide the synthesis of the new complementary polynucleotide of DNA. The DNA single-strand template serves to guide the synthesis of a complementary strand of DNA.
DNA replication begins at a specific site in the DNA molecule called the origin of replication. The enzyme helicase unwinds and separates a portion of the DNA molecule after which single-strand binding proteins react with and stabilize the separated, single-stranded sections of the DNA molecule. The enzyme complex DNA polymerase engages the separated portion of the molecule and initiates the process of replication. DNA polymerase can only connect new DNA nucleotides to a pre-existing chain of nucleotides. Therefore, replication begins as an enzyme called primase assembles an RNA primer at the origin of replication. The RNA primer consists of a short sequence of RNA nucleotides, complementary to a small, initial section of the DNA strand being prepared for replication. DNA polymerase is then able to add DNA nucleotides to the RNA primer and thus begin the process of constructing a new complementary strand of DNA. Later the RNA primer is enzymatically removed and replaced with the appropriate sequence of DNA nucleotides. Because the two complementary strands of the DNA molecule are oriented in opposite directions and the DNA polymerase can only accommodate replication in one direction, two different mechanisms for copying the strands of DNA are employed. One strand is replicated continuously towards unwinding, separating the portion of the original DNA molecule; while the other strand is replicated discontinuously in the opposite direction with the formation of a series of short DNA segments called Okazaki fragments. Each Okazaki fragment requires a separate RNA primer. As the Okazaki fragments are synthesized, the RNA primers are replaced with DNA nucleotides and the fragments are bonded together in a continuous complementary strand.
== DNA damage and repair ==
Damage of nuclear DNA is a persistent problem arising from a variety of disruptive endogenous and exogenous sources. Eukaryotes have evolved a diverse set of DNA repair processes that remove nuclear DNA damages. These repair processes include base excision repair, nucleotide excision repair, homologous recombinational repair, non-homologous end joining and microhomology-mediated end joining. Such repair processes are essential for maintaining nuclear DNA stability. Failure of repair activity to keep up with the occurrence of damages has various negative consequences. Nuclear DNA damages, as well as the mutations and epigenetic alterations that such damages cause, are considered to be a major cause of cancer. Nuclear DNA damages are also implicated in aging and neurodegenerative diseases.
== Mutation ==
Nuclear DNA is subject to mutation. A major cause of mutation is inaccurate DNA replication, often by specialized DNA polymerases that synthesize past DNA damages in the template strand (error-prone trans-lesion synthesis). Mutations also arise by inaccurate DNA repair. The microhomology-mediated end joining pathway for repair of double-strand breaks is particularly prone to mutation. Mutations arising in the nuclear DNA of the germline are most often neutral or adaptively disadvantageous. However, the small proportion of mutations that prove to be advantageous provide the genetic variation upon which natural selection operates to generate new adaptations.
== Gallery ==
The human nuclear DNA displayed into chromosome ideograms with label from Human Genome Project (1990-2003)
== See also ==
Chromatin
Nuclear gene
== References == | Wikipedia/Nuclear_DNA |
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction).
Several review articles have shown that deficient DNA repair, allowing greater accumulation of DNA damage, causes premature aging; and that increased DNA repair facilitates greater longevity, e.g. Mouse models of nucleotide-excision–repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relationship. Human population studies show that single-nucleotide polymorphisms in DNA repair genes, causing up-regulation of their expression, correlate with increases in longevity. Lombard et al. compiled a lengthy list of mouse mutational models with pathologic features of premature aging, all caused by different DNA repair defects. Freitas and de Magalhães presented a comprehensive review and appraisal of the DNA damage theory of aging, including a detailed analysis of many forms of evidence linking DNA damage to aging. As an example, they described a study showing that centenarians of 100 to 107 years of age had higher levels of two DNA repair enzymes, PARP1 and Ku70, than general-population old individuals of 69 to 75 years of age. Their analysis supported the hypothesis that improved DNA repair leads to longer life span. Overall, they concluded that while the complexity of responses to DNA damage remains only partly understood, the idea that DNA damage accumulation with age is the primary cause of aging remains an intuitive and powerful one.
In humans and other mammals, DNA damage occurs frequently and DNA repair processes have evolved to compensate. In estimates made for mice, DNA lesions occur on average 25 to 115 times per minute in each cell, or about 36,000 to 160,000 per cell per day. Some DNA damage may remain in any cell despite the action of repair processes. The accumulation of unrepaired DNA damage is more prevalent in certain types of cells, particularly in non-replicating or slowly replicating cells, such as cells in the brain, skeletal and cardiac muscle.
== DNA damage and mutation ==
To understand the DNA damage theory of aging it is important to distinguish between DNA damage and mutation, the two major types of errors that occur in DNA. Damage and mutation are fundamentally different. DNA damage is any physical abnormality in the DNA, such as single and double strand breaks, 8-hydroxydeoxyguanosine residues and polycyclic aromatic hydrocarbon adducts. DNA damage can be recognized by enzymes, and thus can be correctly repaired using the complementary undamaged strand in DNA as a template or an undamaged sequence in a homologous chromosome if it is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented and thus translation into a protein will also be blocked. Replication may also be blocked and/or the cell may die. Descriptions of reduced function, characteristic of aging and associated with accumulation of DNA damage, are described in the next section.
In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation.
Given these properties of DNA damage and mutation, it can be seen that DNA damages are a special problem in non-dividing or slowly dividing cells, where unrepaired damages will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damages that do not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell's survival. Thus, in a population of cells comprising a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism, because such mutant cells can give rise to cancer. Thus, DNA damages in frequently dividing cells, because they give rise to mutations, are a prominent cause of cancer. In contrast, DNA damages in infrequently dividing cells are likely a prominent cause of aging.
The first person to suggest that DNA damage, as distinct from mutation, is the primary cause of aging was Alexander in 1967. By the early 1980s there was significant experimental support for this idea in the literature. By the early 1990s experimental support for this idea was substantial, and furthermore it had become increasingly evident that oxidative DNA damage, in particular, is a major cause of aging.
In a series of articles from 1970 to 1977, PV Narasimh Acharya, Phd. (1924–1993) theorized and presented evidence that cells undergo "irreparable DNA damage", whereby DNA crosslinks occur when both normal cellular repair processes fail and cellular apoptosis does not occur. Specifically, Acharya noted that double-strand breaks and a "cross-linkage joining both strands at the same point is irreparable because neither strand can then serve as a template for repair. The cell will die in the next mitosis or in some rare instances, mutate."
== Age-associated accumulation of DNA damage and changes in gene expression ==
In tissues composed of non- or infrequently replicating cells, DNA damage can accumulate with age and lead either to loss of cells, or, in surviving cells, loss of gene expression. Accumulated DNA damage is usually measured directly. Numerous studies of this type have indicated that oxidative damage to DNA is particularly important. The loss of expression of specific genes can be detected at both the mRNA level and protein level.
Other form of age-associated changes in gene expression is increased transcriptional variability, that was found first in a selected panel of genes in heart cells and, more recently, in the whole transcriptomes of immune cells, and human pancreas cells.
=== Brain ===
The adult brain is composed in large part of terminally differentiated non-dividing neurons. Many of the conspicuous features of aging reflect a decline in neuronal function. Accumulation of DNA damage with age in the mammalian brain has been reported during the period 1971 to 2008 in at least 29 studies. This DNA damage includes the oxidized nucleoside 8-oxo-2'-deoxyguanosine (8-oxo-dG), single- and double-strand breaks, DNA-protein crosslinks and malondialdehyde adducts (reviewed in Bernstein et al.). Increasing DNA damage with age has been reported in the brains of the mouse, rat, gerbil, rabbit, dog, and human.
Rutten et al. showed that single-strand breaks accumulate in the mouse brain with age. Young 4-day-old rats have about 3,000 single-strand breaks and 156 double-strand breaks per neuron, whereas in rats older than 2 years the level of damage increases to about 7,400 single-strand breaks and 600 double-strand breaks per neuron. Sen et al. showed that DNA damages which block the polymerase chain reaction in rat brain accumulate with age. Swain and Rao observed marked increases in several types of DNA damages in aging rat brain, including single-strand breaks, double-strand breaks and modified bases (8-OHdG and uracil). Wolf et al. also showed that the oxidative DNA damage 8-OHdG accumulates in rat brain with age. Similarly, it was shown that as humans age from 48 to 97 years, 8-OHdG accumulates in the brain.
Lu et al. studied the transcriptional profiles of the human frontal cortex of individuals ranging from 26 to 106 years of age. This led to the identification of a set of genes whose expression was altered after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. In the brain, promoters of genes with reduced expression have markedly increased DNA damage. In cultured human neurons, these gene promoters are selectively damaged by oxidative stress. Thus Lu et al. concluded that DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a program of brain aging that starts early in adult life.
=== Muscle ===
Muscle strength, and stamina for sustained physical effort, decline in function with age in humans and other species. Skeletal muscle is a tissue composed largely of multinucleated myofibers, elements that arise from the fusion of mononucleated myoblasts. Accumulation of DNA damage with age in mammalian muscle has been reported in at least 18 studies since 1971. Hamilton et al. reported that the oxidative DNA damage 8-OHdG accumulates in heart and skeletal muscle (as well as in brain, kidney and liver) of both mouse and rat with age. In humans, increases in 8-OHdG with age were reported for skeletal muscle. Catalase is an enzyme that removes hydrogen peroxide, a reactive oxygen species, and thus limits oxidative DNA damage. In mice, when catalase expression is increased specifically in mitochondria, oxidative DNA damage (8-OHdG) in skeletal muscle is decreased and lifespan is increased by about 20%. These findings suggest that mitochondria are a significant source of the oxidative damages contributing to aging.
Protein synthesis and protein degradation decline with age in skeletal and heart muscle, as would be expected, since DNA damage blocks gene transcription. In 2005, Piec et al. found numerous changes in protein expression in rat skeletal muscle with age, including lower levels of several proteins related to myosin and actin. Force is generated in striated muscle by the interactions between myosin thick filaments and actin thin filaments.
=== Liver ===
Liver hepatocytes do not ordinarily divide and appear to be terminally differentiated, but they retain the ability to proliferate when injured. With age, the mass of the liver decreases, blood flow is reduced, metabolism is impaired, and alterations in microcirculation occur. At least 21 studies have reported an increase in DNA damage with age in liver. For instance, Helbock et al. estimated that the steady state level of oxidative DNA base alterations increased from 24,000 per cell in the liver of young rats to 66,000 per cell in the liver of old rats.
One or two months after inducing DNA double-strand breaks in the livers of young mice, the mice showed multiple symptoms of aging similar to those seen in untreated livers of normally aged control mice.
=== Kidney ===
In kidney, changes with age include reduction in both renal blood flow and glomerular filtration rate, and impairment in the ability to concentrate urine and to conserve sodium and water. DNA damages, particularly oxidative DNA damages, increase with age (at least 8 studies). For instance Hashimoto et al. showed that 8-OHdG accumulates in rat kidney DNA with age.
=== Long-lived stem cells ===
Tissue-specific stem cells produce differentiated cells through a series of increasingly more committed progenitor intermediates. In hematopoiesis (blood cell formation), the process begins with long-term hematopoietic stem cells that self-renew and also produce progeny cells that upon further replication go through a series of stages leading to differentiated cells without self-renewal capacity. In mice, deficiencies in DNA repair appear to limit the capacity of hematopoietic stem cells to proliferate and self-renew with age. Sharpless and Depinho reviewed evidence that hematopoietic stem cells, as well as stem cells in other tissues, undergo intrinsic aging. They speculated that stem cells grow old, in part, as a result of DNA damage. DNA damage may trigger signalling pathways, such as apoptosis, that contribute to depletion of stem cell stocks. This has been observed in several cases of accelerated aging and may occur in normal aging too.
A key aspect of hair loss with age is the aging of the hair follicle. Ordinarily, hair follicle renewal is maintained by the stem cells associated with each follicle. Aging of the hair follicle appears to be due to the DNA damage that accumulates in renewing stem cells during aging.
== Mutation theories of aging ==
A related theory is that mutation, as distinct from DNA damage, is the primary cause of aging. A comparison of somatic mutation rate across several mammal species found that the total number of accumulated mutations at the end of lifespan was roughly equal across a broad range of lifespans. The authors state that this strong relationship between somatic mutation rate and lifespan across different mammalian species suggests that evolution may constrain somatic mutation rates, perhaps by selection acting on different DNA repair pathways.
As discussed above, mutations tend to arise in frequently replicating cells as a result of errors of DNA synthesis when template DNA is damaged, and can give rise to cancer. However, in mice there is no increase in mutation in the brain with aging. Mice defective in a gene (Pms2) that ordinarily corrects base mispairs in DNA have about a 100-fold elevated mutation frequency in all tissues, but do not appear to age more rapidly. On the other hand, mice defective in one particular DNA repair pathway show clear premature aging, but do not have elevated mutation.
One variation of the idea that mutation is the basis of aging, that has received much attention, is that mutations specifically in mitochondrial DNA are the cause of aging. Several studies have shown that mutations accumulate in mitochondrial DNA in infrequently replicating cells with age. DNA polymerase gamma is the enzyme that replicates mitochondrial DNA. A mouse mutant with a defect in this DNA polymerase is only able to replicate its mitochondrial DNA inaccurately, so that it sustains a 500-fold higher mutation burden than normal mice. These mice showed no clear features of rapidly accelerated aging. Overall, the observations discussed in this section indicate that mutations are not the primary cause of aging.
== Dietary restriction ==
In rodents, caloric restriction slows aging and extends lifespan. At least 4 studies have shown that caloric restriction reduces 8-OHdG damages in various organs of rodents. One of these studies showed that caloric restriction reduced accumulation of 8-OHdG with age in rat brain, heart and skeletal muscle, and in mouse brain, heart, kidney and liver. More recently, Wolf et al. showed that dietary restriction reduced accumulation of 8-OHdG with age in rat brain, heart, skeletal muscle, and liver. Thus reduction of oxidative DNA damage is associated with a slower rate of aging and increased lifespan.
== Inherited defects that cause premature aging ==
If DNA damage is the underlying cause of aging, it would be expected that humans with inherited defects in the ability to repair DNA damages should age at a faster pace than persons without such a defect. Numerous examples of rare inherited conditions with DNA repair defects are known. Several of these show multiple striking features of premature aging, and others have fewer such features. Perhaps the most striking premature aging conditions are Werner syndrome (mean lifespan 47 years), Huchinson–Gilford progeria (mean lifespan 13 years), and Cockayne syndrome (mean lifespan 13 years).
Werner syndrome is due to an inherited defect in an enzyme (a helicase and exonuclease) that acts in base excision repair of DNA (e.g. see Harrigan et al.).
Huchinson–Gilford progeria is due to a defect in Lamin A protein which forms a scaffolding within the cell nucleus to organize chromatin and is needed for repair of double-strand breaks in DNA. A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the DNA repair processes of non-homologous end joining and homologous recombination. Mouse cells deficient for maturation of prelamin A show increased DNA damage and chromosome aberrations and are more sensitive to DNA damaging agents.
Cockayne Syndrome is due to a defect in a protein necessary for the repair process, transcription coupled nucleotide excision repair, which can remove damages, particularly oxidative DNA damages, that block transcription.
In addition to these three conditions, several other human syndromes, that also have defective DNA repair, show several features of premature aging. These include ataxia–telangiectasia, Nijmegen breakage syndrome, some subgroups of xeroderma pigmentosum, trichothiodystrophy, Fanconi anemia, Bloom syndrome and Rothmund–Thomson syndrome.
In addition to human inherited syndromes, experimental mouse models with genetic defects in DNA repair show features of premature aging and reduced lifespan.(e.g. refs.) In particular, mutant mice defective in Ku70, or Ku80, or double mutant mice deficient in both Ku70 and Ku80 exhibit early aging. The mean lifespans of the three mutant mouse strains were similar to each other, at about 37 weeks, compared to 108 weeks for the wild-type control. Six specific signs of aging were examined, and the three mutant mice were found to display the same aging signs as the control mice, but at a much earlier age. Cancer incidence was not increased in the mutant mice. Ku70 and Ku80 form the heterodimer Ku protein essential for the non-homologous end joining (NHEJ) pathway of DNA repair, active in repairing DNA double-strand breaks. This suggests an important role of NHEJ in longevity assurance.
=== Defects in DNA repair cause features of premature aging ===
Many authors have noted an association between defects in the DNA damage response and premature aging (see e.g.). If a DNA repair protein is deficient, unrepaired DNA damages tend to accumulate. Such accumulated DNA damages appear to cause features of premature aging (segmental progeria). Table 1 lists 18 DNA repair proteins which, when deficient, cause numerous features of premature aging.
=== Increased DNA repair and extended longevity ===
Table 2 lists DNA repair proteins whose increased expression is connected to extended longevity.
== Lifespan in different mammalian species ==
=== DNA repair capacity ===
Studies comparing DNA repair capacity in different mammalian species have shown that repair capacity correlates with lifespan. The initial study of this type, by Hart and Setlow, showed that the ability of skin fibroblasts of seven mammalian species to perform DNA repair after exposure to a DNA damaging agent correlated with lifespan of the species. The species studied were shrew, mouse, rat, hamster, cow, elephant and human. This initial study stimulated many additional studies involving a wide variety of mammalian species, and the correlation between repair capacity and lifespan generally held up. In one of the more recent studies, Burkle et al. studied the level of a particular enzyme, Poly ADP ribose polymerase, which is involved in repair of single-strand breaks in DNA. They found that the lifespan of 13 mammalian species correlated with the activity of this enzyme.
The DNA repair transcriptomes of the liver of humans, naked mole-rats and mice were compared. The maximum lifespans of humans, naked mole-rat, and mouse are respectively ~120, 30 and 3 years. The longer-lived species, humans and naked mole rats expressed DNA repair genes, including core genes in several DNA repair pathways, at a higher level than did mice. In addition, several DNA repair pathways in humans and naked mole-rats were up-regulated compared with mouse. These findings suggest that increased DNA repair facilitates greater longevity.
Over the past decade, a series of papers have shown that the mitochondrial DNA (mtDNA) base composition correlates with animal species maximum life span. The mitochondrial DNA base composition is thought to reflect its nucleotide-specific (guanine, cytosine, thymidine and adenine) different mutation rates (i.e., accumulation of guanine in the mitochondrial DNA of an animal species is due to low guanine mutation rate in the mitochondria of that species).
=== DNA damage accumulation and repair decline ===
The rate of accumulation of DNA damage (double-strand breaks) in the leukocytes of dolphins, goats, reindeer, American flamingos, and griffon vultures was compared to the longevity of individuals of these different species. The species with longer lifespans were found to have slower accumulation of DNA damage, a finding consistent with the DNA damage theory of aging. In healthy humans after age 50, endogenous DNA single- and double-strand breaks increase linearly, and other forms of DNA damage also increase with age in blood mononuclear cells. Also, after age 50 DNA repair capability decreases with age.
In mice, the DNA repair process of non-homologous end-joining that repairs DNA double strand breaks, declines in efficiency from 1.8-3.8-fold, depending on the specific tissue, when 5 month old animals are compared to 24 month old animals. A study of fibroblast cells from humans varying in age from 16-75 years showed that the efficiency and fidelity of non-homologous end joining, and the efficiency of homologous recombinational DNA repair decline with age leading to increased sensitivity to ionizing radiation in older individuals. In middle aged human adults, oxidative DNA damage was found to be greater among individuals who were both frail and living in poverty.
== Centenarians ==
Lymphoblastoid cell lines established from blood samples of humans who lived past 100 years (centenarians) have significantly higher activity of the DNA repair protein Poly (ADP-ribose) polymerase (PARP) than cell lines from younger individuals (20 to 70 years old). The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after H2O2 sublethal oxidative DNA damage and in their PARP capacity.
Among centenarians, those with the most severe cognitive impairment have the lowest activity of the central DNA repair enzyme apurinic/apyrimidinc (AP) endonuclease 1. AP endonuclease I is employed in the DNA base excision repair pathway and its main role is the repair of damaged or mismatched nucleotides in DNA.
== Menopause ==
As women age, they experience a decline in reproductive performance leading to menopause. This decline is tied to a decline in the number of ovarian follicles. Although 6 to 7 million oocytes are present at mid-gestation in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest are lost. The decline in ovarian reserve appears to occur at an increasing rate with age, and leads to nearly complete exhaustion of the reserve by about age 51. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions.
BRCA1 and BRCA2 are homologous recombination repair genes. The role of declining ATM-Mediated DNA double strand DNA break (DSB) repair in oocyte aging was first proposed by Kutluk Oktay, MD, PhD based on his observations that women with BRCA mutations produced fewer oocytes in response to ovarian stimulation repair. His laboratory has further studied this hypothesis and provided an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Titus et al. from Oktay Laboratory also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in ability to repair double-strand damages can account for the accumulation of these damages, which then likely contributes to the decline in ovarian reserve as further explained by Turan and Oktay.
Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely, suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. Genomic data from about 70,000 women were analyzed to identify protein-coding variation associated with age at natural menopause. Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and including a common coding variant in the BRCA1 gene.
== Atherosclerosis ==
The most important risk factor for cardiovascular problems is chronological aging. Several research groups have reviewed evidence for a key role of DNA damage in vascular aging.
Atherosclerotic plaque contains vascular smooth muscle cells, macrophages and endothelial cells and these have been found to accumulate 8-oxoG, a common type of oxidative DNA damage. DNA strand breaks also increased in atherosclerotic plaques, thus linking DNA damage to plaque formation.
Werner syndrome (WS), a premature aging condition in humans, is caused by a genetic defect in a RecQ helicase that is employed in several DNA repair processes. WS patients develop a substantial burden of atherosclerotic plaques in their coronary arteries and aorta. These findings link excessive unrepaired DNA damage to premature aging and early atherosclerotic plaque development.
== DNA damage and the epigenetic clock ==
Endogenous, naturally occurring DNA damages are frequent, and in humans include an average of about 10,000 oxidative damages per day and 50 double-strand DNA breaks per cell cycle.
Several reviews summarize evidence that the methylation enzyme DNMT1 is recruited to sites of oxidative DNA damage. Recruitment of DNMT1 leads to DNA methylation at the promoters of genes to inhibit transcription during repair. In addition, the 2018 review describes recruitment of DNMT1 during repair of DNA double-strand breaks. DNMT1 localization results in increased DNA methylation near the site of recombinational repair, associated with altered expression of the repaired gene. In general, repair-associated hyper-methylated promoters are restored to their former methylation level after DNA repair is complete. However, these reviews also indicate that transient recruitment of epigenetic modifiers can occasionally result in subsequent stable epigenetic alterations and gene silencing after DNA repair has been completed.
In human and mouse DNA, cytosine followed by guanine (CpG) is the least frequent dinucleotide, making up less than 1% of all dinucleotides (see CG suppression). At most CpG sites cytosine is methylated to form 5-methylcytosine. As indicated in the article CpG site, in mammals, 70% to 80% of CpG cytosines are methylated. However, in vertebrates there are CpG islands, about 300 to 3,000 base pairs long, with interspersed DNA sequences that deviate significantly from the average genomic pattern by being CpG-rich. These CpG islands are predominantly nonmethylated. In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island (see CpG islands in promoters). If the initially nonmethylated CpG sites in a CpG island become largely methylated, this causes stable silencing of the associated gene.
For humans, after adulthood is reached and during subsequent aging, the majority of CpG sequences slowly lose methylation (called epigenetic drift). However, the CpG islands that control promoters tend to gain methylation with age. The gain of methylation at CpG islands in promoter regions is correlated with age, and has been used to create an epigenetic clock (see article Epigenetic clock).
There may be some relationship between the epigenetic clock and epigenetic alterations accumulating after DNA repair. Both unrepaired DNA damage accumulated with age and accumulated methylation of CpG islands would silence genes in which they occur, interfere with protein expression, and contribute to the aging phenotype.
== See also ==
== References == | Wikipedia/DNA_damage_theory_of_aging |
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair.
== Examples ==
DNA-binding proteins include transcription factors which modulate the process of transcription, various polymerases, nucleases which cleave DNA molecules, and histones which are involved in chromosome packaging and transcription in the cell nucleus. DNA-binding proteins can incorporate such domains as the zinc finger, the helix-turn-helix, and the leucine zipper (among many others) that facilitate binding to nucleic acid. There are also more unusual examples such as transcription activator like effectors.
== Non-specific DNA-protein interactions ==
Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones. In prokaryotes, multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group (HMG) proteins, which bind to bent or distorted DNA. Biophysical studies show that these architectural HMG proteins bind, bend and loop DNA to perform its biological functions. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that form chromosomes. Recently FK506 binding protein 25 (FBP25) was also shown to non-specifically bind to DNA which helps in DNA repair.
== Proteins that specifically bind single-stranded DNA ==
A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.
== Binding to specific DNA sequences ==
In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.
These DNA targets can occur throughout an organism's genome. Thus, changes in the activity of one type of transcription factor can affect thousands of genes. Thus, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to read the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible. Mathematical descriptions of protein-DNA binding taking into account sequence-specificity, and competitive and cooperative binding of proteins of different types are usually performed with the help of the lattice models. Computational methods to identify the DNA binding sequence specificity have been proposed to make a good use of the abundant sequence data in the post-genomic era. In addition, progress has happened on structure-based prediction of binding specificity across protein families using deep learning.
== Protein–DNA interactions ==
Protein–DNA interactions occur when a protein binds a molecule of DNA, often to regulate the biological function of DNA, usually the expression of a gene. Among the proteins that bind to DNA are transcription factors that activate or repress gene expression by binding to DNA motifs and histones that form part of the structure of DNA and bind to it less specifically. Also proteins that repair DNA such as uracil-DNA glycosylase interact closely with it.
In general, proteins bind to DNA in the major groove; however, there are exceptions. Protein–DNA interaction are of mainly two types, either specific interaction, or non-specific interaction. Recent single-molecule experiments showed that DNA binding proteins undergo of rapid rebinding in order to bind in correct orientation for recognizing the target site.
=== Design ===
Designing DNA-binding proteins that have a specified DNA-binding site has been an important goal for biotechnology. Zinc finger proteins have been designed to bind to specific DNA sequences and this is the basis of zinc finger nucleases. Recently transcription activator-like effector nucleases (TALENs) have been created which are based on natural proteins secreted by Xanthomonas bacteria via their type III secretion system when they infect various plant species.
=== Detection methods ===
There are many in vitro and in vivo techniques which are useful in detecting DNA-Protein Interactions. The following lists some methods currently in use: Electrophoretic mobility shift assay (EMSA) is a widespread qualitative technique to study protein–DNA interactions of known DNA binding proteins. DNA-Protein-Interaction - Enzyme-Linked ImmunoSorbant Assay (DPI-ELISA) allows the qualitative and quantitative analysis of DNA-binding preferences of known proteins in vitro. This technique allows the analysis of protein complexes that bind to DNA (DPI-Recruitment-ELISA) or is suited for automated screening of several nucleotide probes due to its standard ELISA plate formate. DNase footprinting assay can be used to identify the specific sites of binding of a protein to DNA at basepair resolution. Chromatin immunoprecipitation is used to identify the in vivo DNA target regions of a known transcription factor. This technique when combined with high throughput sequencing is known as ChIP-Seq and when combined with microarrays it is known as ChIP-chip. Yeast one-hybrid System (Y1H) is used to identify which protein binds to a particular DNA fragment. Bacterial one-hybrid system (B1H) is used to identify which protein binds to a particular DNA fragment. Structure determination using X-ray crystallography has been used to give a highly detailed atomic view of protein–DNA interactions.
Besides these methods, other techniques such as SELEX, PBM (protein binding microarrays), DNA microarray screens, DamID, FAIRE or more recently DAP-seq are used in the laboratory to investigate DNA-protein interaction in vivo and in vitro.
=== Manipulating the interactions ===
The protein–DNA interactions can be modulated using stimuli like ionic strength of the buffer, macromolecular crowding, temperature, pH and electric field. This can lead to reversible dissociation/association of the protein–DNA complex.
== See also ==
bZIP domain
ChIP-exo
Comparison of nucleic acid simulation software
DNA-binding domain
Helix-loop-helix
Helix-turn-helix
HMG-box
Leucine zipper
Lexitropsin (a semi-synthetic DNA-binding ligand)
Deoxyribonucleoprotein
Protein–DNA interaction site prediction software
RNA-binding protein
Single-strand binding protein
Zinc finger
== References ==
== External links ==
Protein-DNA binding: data, tools & models (annotated list, constantly updated)
Abalone tool for modeling DNA-ligand interactions.
DBD database of predicted transcription factors Uses a curated set of DNA-binding domains to predict transcription factors in all completely sequenced genomes
DNA-Binding+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/DNA-binding_protein |
DNA digital data storage is the process of encoding and decoding binary data to and from synthesized strands of DNA.
While DNA as a storage medium has enormous potential because of its high storage density, its practical use is currently severely limited because of its high cost and very slow read and write times.
In June 2019, scientists reported that all 16 GB of text from the English Wikipedia had been encoded into synthetic DNA. In 2021, scientists reported that a custom DNA data writer had been developed that was capable of writing data into DNA at 1 Mbps.
== Encoding methods ==
Many methods for encoding data in DNA are possible. The optimal methods are those that make economical use of DNA and protect against errors. If the message DNA is intended to be stored for a long period of time, for example, 1,000 years, it is also helpful if the sequence is obviously artificial and the reading frame is easy to identify.
=== Encoding text ===
Several simple methods for encoding text have been proposed. Most of these involve translating each letter into a corresponding "codon", consisting of a unique small sequence of nucleotides in a lookup table. Some examples of these encoding schemes include Huffman codes, comma codes, and alternating codes.
=== Encoding arbitrary data ===
To encode arbitrary data in DNA, the data is typically first converted into ternary (base 3) data rather than binary (base 2) data. Each digit (or "trit") is then converted to a nucleotide using a lookup table. To prevent homopolymers (repeating nucleotides), which can cause problems with accurate sequencing, the result of the lookup also depends on the preceding nucleotide. Using the example lookup table below, if the previous nucleotide in the sequence is T (thymine), and the trit is 2, the next nucleotide will be G (guanine).
Various systems may be incorporated to partition and address the data, as well as to protect it from errors. One approach to error correction is to regularly intersperse synchronization nucleotides between the information-encoding nucleotides. These synchronization nucleotides can act as scaffolds when reconstructing the sequence from multiple overlapping strands.
== In vivo ==
The genetic code within living organisms can potentially be co-opted to store information. Furthermore synthetic biology can be used to engineer cells with "molecular recorders" to allow the storage and retrieval of information stored in the cell's genetic material. CRISPR gene editing can also be used to insert artificial DNA sequences into the genome of the cell. For encoding developmental lineage data (molecular flight recorder), roughly 30 trillion cell nuclei per mouse * 60 recording sites per nucleus * 7-15 bits per site yields about 2 terabytes per mouse written (but only very selectively read).
=== In-vivo light-based direct image and data recording ===
A proof-of-concept in-vivo direct DNA data recording system was demonstrated through incorporation of optogenetically regulated recombinases as part of an engineered "molecular recorder" allows for direct encoding of light-based stimuli into engineered E.coli cells. This approach can also be parallelized to store and write text or data in 8-bit form through the use of physically separated individual cell cultures in cell-culture plates.
This approach leverages the editing of a "recorder plasmid" by the light-regulated recombinases, allowing for identification of cell populations exposed to different stimuli. This approach allows for the physical stimulus to be directly encoded into the "recorder plasmid" through recombinase action. Unlike other approaches, this approach does not require manual design, insertion and cloning of artificial sequences to record the data into the genetic code. In this recording process, each individual cell population in each cell-culture plate culture well can be treated as a digital "bit", functioning as a biological transistor capable of recording a single bit of data.
== History ==
The idea of DNA digital data storage dates back to 1959, when the physicist Richard P. Feynman, in "There's Plenty of Room at the Bottom: An Invitation to Enter a New Field of Physics" outlined the general prospects for the creation of artificial objects similar to objects of the microcosm (including biological) and having similar or even more extensive capabilities. In 1964–65, Mikhail Samoilovich Neiman, the Soviet physicist, published 3 articles about microminiaturization in electronics at the molecular-atomic level, which independently presented general considerations and some calculations regarding the possibility of recording, storage, and retrieval of information on synthesized DNA and RNA molecules. After the publication of the first M.S. Neiman's paper and after receiving by Editor the manuscript of his second paper (January, the 8th, 1964, as indicated in that paper) the interview with cybernetician Norbert Wiener was published. N. Wiener expressed ideas about miniaturization of computer memory, close to the ideas, proposed by M. S. Neiman independently. These Wiener's ideas M. S. Neiman mentioned in the third of his papers. This story is described in details.
One of the earliest uses of DNA storage occurred in a 1988 collaboration between artist Joe Davis and researchers from Harvard University. The image, stored in a DNA sequence in E.coli, was organized in a 5 x 7 matrix that, once decoded, formed a picture of an ancient Germanic rune representing life and the female Earth. In the matrix, ones corresponded to dark pixels while zeros corresponded to light pixels.
In 2007 a device was created at the University of Arizona using addressing molecules to encode mismatch sites within a DNA strand. These mismatches were then able to be read out by performing a restriction digest, thereby recovering the data.
In 2011, George Church, Sri Kosuri, and Yuan Gao carried out an experiment that would encode a 659 kb book that was co-authored by Church. To do this, the research team did a two-to-one correspondence where a binary zero was represented by either an adenine or cytosine and a binary one was represented by a guanine or thymine. After examination, 22 errors were found in the DNA.
In 2012, George Church and colleagues at Harvard University published an article in which DNA was encoded with digital information that included an HTML draft of a 53,400 word book written by the lead researcher, eleven JPEG images and one JavaScript program. Multiple copies for redundancy were added and 5.5 petabits can be stored in each cubic millimeter of DNA. The researchers used a simple code where bits were mapped one-to-one with bases, which had the shortcoming that it led to long runs of the same base, the sequencing of which is error-prone. This result showed that besides its other functions, DNA can also be another type of storage medium such as hard disk drives and magnetic tapes.
In 2013, an article led by researchers from the European Bioinformatics Institute (EBI) and submitted at around the same time as the paper of Church and colleagues detailed the storage, retrieval, and reproduction of over five million bits of data. All the DNA files reproduced the information with an accuracy between 99.99% and 100%. The main innovations in this research were the use of an error-correcting encoding scheme to ensure the extremely low data-loss rate, as well as the idea of encoding the data in a series of overlapping short oligonucleotides identifiable through a sequence-based indexing scheme. Also, the sequences of the individual strands of DNA overlapped in such a way that each region of data was repeated four times to avoid errors. Two of these four strands were constructed backwards, also with the goal of eliminating errors. The costs per megabyte were estimated at $12,400 to encode data and $220 for retrieval. However, it was noted that the exponential decrease in DNA synthesis and sequencing costs, if it continues into the future, should make the technology cost-effective for long-term data storage by 2023.
In 2013, a software called DNACloud was developed by Manish K. Gupta and co-workers to encode computer files to their DNA representation. It implements a memory efficiency version of the algorithm proposed by Goldman et al. to encode (and decode) data to DNA (.dnac files).
The long-term stability of data encoded in DNA was reported in February 2015, in an article by researchers from ETH Zurich. The team added redundancy via Reed–Solomon error correction coding and by encapsulating the DNA within silica glass spheres via Sol-gel chemistry.
In 2016 research by Church and Technicolor Research and Innovation was published in which, 22 MB of a MPEG compressed movie sequence were stored and recovered from DNA. The recovery of the sequence was found to have zero errors.
In March 2017, Yaniv Erlich and Dina Zielinski of Columbia University and the New York Genome Center published a method known as DNA Fountain that stored data at a density of 215 petabytes per gram of DNA. The technique approaches the Shannon capacity of DNA storage, achieving 85% of the theoretical limit. The method was not ready for large-scale use, as it costs $7000 to synthesize 2 megabytes of data and another $2000 to read it.
In March 2018, University of Washington and Microsoft published results demonstrating storage and retrieval of approximately 200MB of data. The research also proposed and evaluated a method for random access of data items stored in DNA. In March 2019, the same team announced they have demonstrated a fully automated system to encode and decode data in DNA.
Research published by Eurecom and Imperial College in January 2019, demonstrated the ability to store structured data in synthetic DNA. The research showed how to encode structured or, more specifically, relational data in synthetic DNA and also demonstrated how to perform data processing operations (similar to SQL) directly on the DNA as chemical processes.
In April 2019, due to a collaboration with TurboBeads Labs in Switzerland, Mezzanine by Massive Attack was encoded into synthetic DNA, making it the first album to be stored in this way.
In June 2019, scientists reported that all 16 GB of Wikipedia have been encoded into synthetic DNA. In 2021, CATALOG reported that they had developed a custom DNA writer capable of writing data at 1 Mbps into DNA.
The first article describing data storage on native DNA sequences via enzymatic nicking was published in April 2020. In the paper, scientists demonstrate a new method of recording information in DNA backbone which enables bit-wise random access and in-memory computing.
In 2021, a research team at Newcastle University led by N. Krasnogor implemented a stack data structure using DNA, allowing for last-in, first-out (LIFO) data recording and retrieval. Their approach used hybridization and strand displacement to record DNA signals in DNA polymers, which were then released in reverse order. The study demonstrated that data structure-like operations are possible in the molecular realm. The researchers also explored the limitations and future improvements for dynamic DNA data structures, highlighting the potential for DNA-based computational systems.
== Davos Bitcoin Challenge ==
On January 21, 2015, Nick Goldman from the European Bioinformatics Institute (EBI), one of the original authors of the 2013 Nature paper, announced the Davos Bitcoin Challenge at the World Economic Forum annual meeting in Davos. During his presentation, DNA tubes were handed out to the audience, with the message that each tube contained the private key of exactly one bitcoin, all coded in DNA. The first one to sequence and decode the DNA could claim the bitcoin and win the challenge. The challenge was set for three years and would close if nobody claimed the prize before January 21, 2018.
Almost three years later on January 19, 2018, the EBI announced that a Belgian PhD student, Sander Wuyts, of the University of Antwerp and Vrije Universiteit Brussel, was the first one to complete the challenge. Next to the instructions on how to claim the bitcoin (stored as a plain text and PDF file), the logo of the EBI, the logo of the company that printed the DNA (CustomArray), and a sketch of James Joyce were retrieved from the DNA.
== The Lunar Library ==
The Lunar Library, launched on the Beresheet Lander by the Arch Mission Foundation, carries information encoded in DNA, which includes 20 famous books and 10,000 images. This was one of the optimal choices of storage, as DNA can last a long time. The Arch Mission Foundation suggests that it can still be read after billions of years.
The lander crashed on 11 April 2019 and was lost.
== DNA of things ==
The concept of the DNA of Things (DoT) was introduced in 2019 by a team of researchers from Israel and Switzerland, including Yaniv Erlich and Robert Grass. DoT encodes digital data into DNA molecules, which are then embedded into objects. This gives the ability to create objects that carry their own blueprint, similar to biological organisms. In contrast to Internet of things, which is a system of interrelated computing devices, DoT creates objects which are independent storage objects, completely off-grid.
As a proof of concept for DoT, the researcher 3D-printed a Stanford bunny which contains its blueprint in the plastic filament used for printing. By clipping off a tiny bit of the ear of the bunny, they were able to read out the blueprint, multiply it and produce a next generation of bunnies. In addition, the ability of DoT to serve for steganographic purposes was shown by producing non-distinguishable lenses which contain a YouTube video integrated into the material.
== See also ==
DNA computing
DNA nanotechnology
Nanobiotechnology
Natural computing
Plant-based digital data storage
5D optical data storage
== References ==
== Further reading == | Wikipedia/DNA_digital_data_storage |
Multicopy single-stranded DNA (msDNA) is a type of extrachromosomal satellite DNA that consists of a single-stranded DNA molecule covalently linked via a 2'-5'phosphodiester bond to an internal guanosine of an RNA molecule. The resultant DNA/RNA chimera possesses two stem-loops joined by a branch similar to the branches found in RNA splicing intermediates. The coding region for msDNA, called a "retron", also encodes a type of reverse transcriptase, which is essential for msDNA synthesis.
== Discovery ==
Before the discovery of msDNA in myxobacteria, a group of swarming, soil-dwelling bacteria, it was thought that the enzymes known as reverse transcriptases (RT) existed only in eukaryotes and viruses. The discovery led to an increase in research of the area. As a result, msDNA has been found to be widely distributed among bacteria, including various strains of Escherichia coli and pathogenic bacteria. Further research discovered similarities between HIV-encoded reverse transcriptase and an open reading frame (ORF) found in the msDNA coding region. Tests confirmed the presence of reverse transcriptase activity in crude lysates of retron-containing strains. Although an RNase H domain was tentatively identified in the retron ORF, it was later found that the RNase H activity required for msDNA synthesis is actually supplied by the host.
== Retrons ==
The discovery of msDNA has led to broader questions regarding where reverse transcriptase originated, as genes encoding for reverse transcriptase (not necessarily associated with msDNA) have been found in prokaryotes, eukaryotes, viruses and even archaea. After a DNA fragment coding for the production of msDNA in E. coli was discovered, it was conjectured that bacteriophages might have been responsible for the introduction of the RT gene into E. coli. These discoveries suggest that reverse transcriptase played a role in the evolution of viruses from bacteria, with one hypothesis stating that, with the help of reverse transcriptase, viruses may have arisen as a breakaway msDNA gene that acquired a protein coat. Since nearly all RT genes function in retrovirus replication and/or the movement of transposable elements, it is reasonable to imagine that retrons might be mobile genetic elements, but there has been little supporting evidence for such a hypothesis, save for the observed fact that msDNA is widely yet sporadically dispersed among bacterial species in a manner suggestive of both horizontal and vertical transfer. Since it is not known whether retron sequences per se represent mobile elements, retrons are functionally defined by their ability to produce msDNA while deliberately avoiding speculation about other possible activities.
== Function ==
The function of msDNA remains unknown even though many copies are present within cells. Knockout mutations that do not express msDNA are viable, so the production of msDNA is not essential to life under laboratory conditions. Over-expression of msDNA is mutagenic, apparently as a result of titrating out repair proteins by the mismatched base pairs that are typical of their structure. It has been suggested that msDNA may have some role in pathogenicity or the adaptation to stressful conditions. Sequence comparison of msDNAs from Myxococcus xanthus, Stigmatella aurantiaca, and many other bacteria reveal conserved and hypervariable domains reminiscent of conserved and hypervariable sequences found in allorecognition molecules. The major msDNAs of M. xanthus and S. aurantiaca, for instance, share 94% sequence homology except within a 19 base-pair domain that shares sequence homology of only 42%. The presence of such domains is significant because myxobacteria exhibit complex cooperative social behaviors including swarming and formation of fruiting bodies, while E. coli and other pathogenic bacteria form biofilms that exhibit enhanced antibiotic and detergent resistance. The sustainability of social assemblies that require significant individual investment of energy is generally dependent on the evolution of allorecognition mechanisms that enable groups to distinguish self versus non-self.
== Biosynthesis ==
Biosynthesis of msDNA is purported to follow a unique pathway found nowhere else in DNA/RNA biochemistry. Because of the similarity of the 2'-5' branch junction to the branch junctions found in RNA splicing intermediates, it might at first have been expected that branch formation would be via spliceosome- or ribozyme-mediated ligation. Surprisingly, however, experiments in cell-free systems using purified retron reverse transcriptase indicate that cDNA synthesis is directly primed from the 2'-OH group of the specific internal G residue of the primer RNA. The RT recognizes specific stem-loop structures in the precursor RNA, rendering synthesis of msDNA by the RT highly specific to its own retron. The priming of msDNA synthesis offers a fascinating challenge to our understanding of DNA synthesis. DNA polymerases (which include RT) share highly conserved structural features, which means that their active catalytic sites vary little from species to species, or even between DNA polymerases using DNA as a template, versus DNA polymerases using RNA as a template. The catalytic region of eukaryotic reverse transcriptase comprises three domains termed the "fingers", "palm", and "thumb" which hold the double-stranded primer-template in a right-hand grip with the 3'-OH of the primer buried in the active site of the polymerase, a cluster of highly conserved acidic and polar residues situated on the palm between what would be the index and middle fingers. In eukaryotic RTs, the RNase H domain lies on the wrist below the base of the thumb, but retron RTs lack RNase H activity. The nucleic acid binding cleft, extending from the polymerase active site to the RNase H active site, is about 60 Å in length in eukaryotic RTs, corresponding to nearly two helical turns. When eukaryotic RT extends a conventional primer, the growing DNA/RNA double helix spirals along the cleft, and as the double helix passes the RNase H domain, the template RNA is digested to release the nascent strand of cDNA. In the case of msDNA primer extension, however, a long strand of RNA remains attached to the 3'-OH of the priming G. Although it is possible to model an RT-primer template complex which would make the 2'-OH accessible for the priming reaction, further extension of the DNA strand presents a problem: as DNA synthesis progresses, the bulky RNA strand extending from the 3'-OH needs somehow to spiral down the binding cleft without being blocked by steric hindrance. To overcome this issue, the msDNA reverse transcriptase clearly would require special features not shared by other RTs.
== References ==
== Further reading ==
Lampson B, Inouye M, Inouye S (2001). The msDNAs of bacteria. Progress in Nucleic Acid Research and Molecular Biology. Vol. 67. pp. 65–91. doi:10.1016/S0079-6603(01)67025-9. ISBN 9780125400671. PMID 11525386.
Zimmerly, Steven (2005). "Mobile introns and retroelements in bacteria". In Mullany, Peter (ed.). The Dynamic Bacterial Genome. Advances in Molecular and Cellular Microbiology. Vol. 8. Cambridge University Press. pp. 121–148. doi:10.1017/CBO9780511541544.004. ISBN 978-0-511-54154-4. | Wikipedia/Multicopy_single-stranded_DNA |
Hachimoji DNA (from Japanese 八文字 hachimoji, "eight letters") is a synthetic nucleic acid analog that uses four synthetic nucleotides in addition to the four present in the natural nucleic acids, DNA and RNA. This leads to four allowed base pairs: two unnatural base pairs formed by the synthetic nucleobases in addition to the two normal pairs. Hachimoji bases have been demonstrated in both DNA and RNA analogs, using deoxyribose and ribose respectively as the backbone sugar.
Benefits of such a nucleic acid system may include an enhanced ability to store data, as well as insights into what may be possible in the search for extraterrestrial life.
The hachimoji DNA system produced one type of catalytic RNA (ribozyme or aptamer) in vitro.
== Description ==
Natural DNA is a molecule carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life. DNA is a polynucleotide as it is composed of simpler monomeric units called nucleotides; when double-stranded, the two chains coil around each other to form a double helix.
In natural DNA, each nucleotide is composed of one of four nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound to each other with hydrogen bonds, according to base pairing rules (A with T and C with G), to make double-stranded DNA.
Hachimoji DNA is similar to natural DNA but differs in the number, and type, of nucleobases. Unnatural nucleobases, more hydrophobic than natural bases, are used in successful hachimoji DNA. Such a DNA always formed the standard double helix, no matter what sequence of bases were used. An enzyme (T7 polymerase) was adapted by the researchers to be used in vitro to transcribe hachimoji DNA into hachimoji RNA, which, in turn, produced chemical activity in the form of a glowing green fluorophore.
=== New base pairs ===
DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hachimoji DNA uses an additional four synthetic nucleotides to form four types of base pairs, two of which are unnatural: P binds with Z and B binds with S (dS in DNA, rS in RNA).
=== Background ===
Earlier, the research group responsible for the hachimoji DNA system, headed by Harvard University chemist Steven Benner, had studied a synthetic DNA analog system, named Artificially Expanded Genetic Information System (AEGIS), that used twelve different nucleotides, including the four found in DNA.
== Biology ==
Scripps Research chemist Floyd Romesberg, noted for creating the first Unnatural Base Pair (UBP), and expanding the genetic alphabet of four letters to six in 2012, stated that the invention of the hachimoji DNA system is an example of the fact that the natural bases (G, C, A and T) "are not unique". Creating new life forms may be possible, at least theoretically, with the new DNA system. For now, however, the hachimoji DNA system is not self-sustaining; the system needs a steady supply of unique building blocks and proteins found only in the laboratory. As a result, "Hachimoji DNA can go nowhere if it escapes the laboratory."
== Applications ==
NASA funded this research to "expand[s] the scope of the structures that we might encounter as we search for life in the cosmos". According to Lori Glaze of the Planetary Science Division of NASA, "Life detection is an increasingly important goal of NASA's planetary science missions, and this new work [with hachimoji DNA] will help us to develop effective instruments and experiments that will expand the scope of what we look for." Research team leader Steven Benner notes, "By carefully analyzing the roles of shape, size and structure in hachimoji DNA, this work expands our understanding of the types of molecules that might store information in extraterrestrial life on alien worlds."
According to researchers, hachimoji DNA could also be used "to develop clean diagnostics for human diseases, in DNA digital data storage, DNA barcoding, self-assembling nanostructures, and to make proteins with unusual amino acids. Parts of this hachimoji DNA are already being commercially produced by Firebird Biomolecular Sciences LLC".
== See also ==
== References ==
== Further reading ==
Bains W (2004). "Many chemistries could be used to build living systems" (PDF). Astrobiology. 4 (2): 137–67. Bibcode:2004AsBio...4..137B. doi:10.1089/153110704323175124. PMID 15253836. S2CID 27477952. Hypothesis paper.
== External links ==
Astronomy FAQ - Why do we assume that other beings must be based on carbon? Why couldn't organisms be based on other substances?
Film clip encoded into DNA using CRISPR: video (01:39) on YouTube | Wikipedia/Hachimoji_DNA |
In biology, a branched DNA assay is a signal amplification assay (as opposed to a target amplification assay) that is used to detect nucleic acid molecules.
== Method ==
A branched DNA assay begins with a dish or some other solid support (e.g., a plastic dipstick). The dish is peppered with small, single stranded DNA molecules (or chains) that stick out into the solution. These are known as capture probe DNA molecules. Next, an extender DNA molecule is added. Each extender has two domains; one that hybridizes to the capture DNA molecule and one that sticks out above the surface. The purpose of the extender is two-fold. First, it creates more available surface area for target DNA molecules to bind, and second, it allows the assay to be easily adapted to detect a variety of target DNA molecules.
Once the capture and extender molecules are in place and they have hybridized, the sample can be added. Target molecules in the sample will bind to the extender molecule. This results in a base peppered with capture probes, which are hybridized to extender probes, which in turn are hybridized to target molecules.
At this point, signal amplification takes place. A label extender DNA molecule is added that has two domains (similar to the first extender). The label extender hybridizes to the target and to a pre-amplified molecule. The preamplifier molecule has two domains. First, it binds to the label extender and second, it binds to the amplifier molecule. An example amplifier molecule is an oligonucleotide chain bound to the enzyme alkaline phosphatase.
Diagrammatically, the process can be resembled as
Base → Capture Probe → Extender → Target → label extender → pre-amplifier → amplifier
== Uses and Advantages ==
The assay can be used to detect and quantify many types of RNA or DNA target. In the assay, branched DNA is mixed with a sample to be tested. The detection is done using a non-radioactive method and does not require preamplification of the nucleic acid to be detected. The assay entirely relies on hybridization. Enzymes are used to indicate the extent of hybridization but are not used to manipulate the nucleic acids. Thus, small amounts of a nucleic acid can be detected and quantified without a reverse transcription step (in the case of RNA) and/or PCR. The assay can be run as a high throughput assay, unlike quantitative Northern-blotting or the RNAse-protection assay, which are labor-intensive and thus difficult to perform on a large number of samples. The other major high throughput technique employed in the quantification of specific RNA molecules is quantitative PCR, after reverse transcription of the RNA to cDNA.
Several different short single-stranded DNA molecules (oligonucleotides) are used in a branched DNA-assay. The capture and capture-extender oligonucleotide bind to the target nucleic acid and immobilize it on a solid support. The label oligonucleotide and the branched DNA then detects the immobilized target nucleic acid. The immobilization of the target on a solid support makes extensive washing easier, which reduces false positive results. After binding of the target to the solid support it can be detected by branched DNA which is coupled to an enzyme (e.g. alkaline phosphatase). The branched DNA binds to the sample nucleic acid by specific hybridization in areas which are not occupied by capture hybrids. The branching of the DNA allows for very dense decorating of the DNA with the enzyme, which is important for the high sensitivity of the assay. The enzyme catalyzes a reaction of a substrate which generates light (detectable in a luminometer). The amount of light emitted increases with the amount of the specific nucleic acid present in the sample. The design of the branched DNA and the way it is hybridized to the nucleic acid to be investigated differs between different generations of the bDNA assay.
Despite the fact that the starting material is not preamplified, bDNA assays can detect less than 100 copies of HIV-RNA per mL of blood. A recent publication in Nature Scientific Reports uses levels of cfDNA as a predictor of chemotherapy efficacy in treatment of advanced cancers, and uses the branched DNA approach to amplify signal of the trace occurring cfDNA.
== See also ==
Dendrimer
== Notes and references ==
== External links ==
Branched+DNA+Assay at the U.S. National Library of Medicine Medical Subject Headings (MeSH) | Wikipedia/Branched_DNA |
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regulatory RNAs). Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional, such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Regions that are completely nonfunctional are called junk DNA.
== Fraction of non-coding genomic DNA ==
In bacteria, the coding regions typically take up 88% of the genome. The remaining 12% does not encode proteins, but much of it still has biological function through genes where the RNA transcript is functional (non-coding genes) and regulatory sequences, which means that almost all of the bacterial genome has a function. The amount of coding DNA in eukaryotes is usually a much smaller fraction of the genome because eukaryotic genomes contain large amounts of repetitive DNA not found in prokaryotes. The human genome contains somewhere between 1–2% coding DNA. The exact number is not known because there are disputes over the number of functional coding exons and over the total size of the human genome. This means that 98–99% of the human genome consists of non-coding DNA and this includes many functional elements such as non-coding genes and regulatory sequences.
Genome size in eukaryotes can vary over a wide range, even between closely related species. This puzzling observation was originally known as the C-value Paradox where "C" refers to the haploid genome size. The paradox was resolved with the discovery that most of the differences were due to the expansion and contraction of repetitive DNA and not the number of genes. Some researchers speculated that this repetitive DNA was mostly junk DNA. The reasons for the changes in genome size are still being worked out and this problem is called the C-value Enigma.
This led to the observation that the number of genes does not seem to correlate with perceived notions of complexity because the number of genes seems to be relatively constant, an issue termed the G-value Paradox. For example, the genome of the unicellular Polychaos dubium (formerly known as Amoeba dubia) has been reported to contain more than 200 times the amount of DNA in humans (i.e. more than 600 billion pairs of bases vs a bit more than 3 billion in humans). The pufferfish Takifugu rubripes genome is only about one eighth the size of the human genome, yet seems to have a comparable number of genes. Genes take up about 30% of the pufferfish genome and the coding DNA is about 10%. (Non-coding DNA = 90%.) The reduced size of the pufferfish genome is due to a reduction in the length of introns and less repetitive DNA.
Utricularia gibba, a bladderwort plant, has a very small nuclear genome (100.7 Mb) compared to most plants. It likely evolved from an ancestral genome that was 1,500 Mb in size. The bladderwort genome has roughly the same number of genes as other plants but the total amount of coding DNA comes to about 30% of the genome.
The remainder of the genome (70% non-coding DNA) consists of promoters and regulatory sequences that are shorter than those in other plant species. The genes contain introns but there are fewer of them and they are smaller than the introns in other plant genomes. There are noncoding genes, including many copies of ribosomal RNA genes. The genome also contains telomere sequences and centromeres as expected. Much of the repetitive DNA seen in other eukaryotes has been deleted from the bladderwort genome since that lineage split from those of other plants. About 59% of the bladderwort genome consists of transposon-related sequences but since the genome is so much smaller than other genomes, this represents a considerable reduction in the amount of this DNA. The authors of the original 2013 article note that claims of additional functional elements in the non-coding DNA of animals do not seem to apply to plant genomes.
According to a New York Times article, during the evolution of this species, "... genetic junk that didn't serve a purpose was expunged, and the necessary stuff was kept." According to Victor Albert of the University of Buffalo, the plant is able to expunge its so-called junk DNA and "have a perfectly good multicellular plant with lots of different cells, organs, tissue types and flowers, and you can do it without the junk. Junk is not needed."
== Types of non-coding DNA sequences ==
=== Noncoding genes ===
There are two types of genes: protein coding genes and noncoding genes. Noncoding genes are an important part of non-coding DNA and they include genes for transfer RNA and ribosomal RNA. These genes were discovered in the 1960s. Prokaryotic genomes contain genes for a number of other noncoding RNAs but noncoding RNA genes are much more common in eukaryotes.
Typical classes of noncoding genes in eukaryotes include genes for small nuclear RNAs (snRNAs), small nucleolar RNAs (sno RNAs), microRNAs (miRNAs), short interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and long noncoding RNAs (lncRNAs). In addition, there are a number of unique RNA genes that produce catalytic RNAs.
Noncoding genes account for only a few percent of prokaryotic genomes but they can represent a vastly higher fraction in eukaryotic genomes. In humans, the noncoding genes take up at least 6% of the genome, largely because there are hundreds of copies of ribosomal RNA genes. Protein-coding genes occupy about 38% of the genome; a fraction that is much higher than the coding region because genes contain large introns.
The total number of noncoding genes in the human genome is controversial. Some scientists think that there are only about 5,000 noncoding genes while others believe that there may be more than 100,000 (see the article on Non-coding RNA). The difference is largely due to debate over the number of lncRNA genes.
=== Promoters and regulatory elements ===
Promoters are DNA segments near the 5' end of the gene where transcription begins. They are the sites where RNA polymerase binds to initiate RNA synthesis. Every gene has a noncoding promoter.
Regulatory elements are sites that control the transcription of a nearby gene. They are almost always sequences where transcription factors bind to DNA and these transcription factors can either activate transcription (activators) or repress transcription (repressors). Regulatory elements were discovered in the 1960s and their general characteristics were worked out in the 1970s by studying specific transcription factors in bacteria and bacteriophage.
Promoters and regulatory sequences represent an abundant class of noncoding DNA but they mostly consist of a collection of relatively short sequences so they do not take up a very large fraction of the genome. The exact amount of regulatory DNA in mammalian genome is unclear because it is difficult to distinguish between spurious transcription factor binding sites and those that are functional. The binding characteristics of typical DNA-binding proteins were characterized in the 1970s and the biochemical properties of transcription factors predict that in cells with large genomes, the majority of binding sites will not be biologically functional.
Many regulatory sequences occur near promoters, usually upstream of the transcription start site of the gene. Some occur within a gene and a few are located downstream of the transcription termination site. In eukaryotes, there are some regulatory sequences that are located at a considerable distance from the promoter region. These distant regulatory sequences are often called enhancers but there is no rigorous definition of enhancer that distinguishes it from other transcription factor binding sites.
=== Introns ===
Introns are the parts of a gene that are transcribed into the precursor RNA sequence, but ultimately removed by RNA splicing during the processing to mature RNA. Introns are found in both types of genes: protein-coding genes and noncoding genes. They are present in prokaryotes but they are much more common in eukaryotic genomes.
Group I and group II introns take up only a small percentage of the genome when they are present. Spliceosomal introns (see Figure) are only found in eukaryotes and they can represent a substantial proportion of the genome. In humans, for example, introns in protein-coding genes cover 37% of the genome. Combining that with about 1% coding sequences means that protein-coding genes occupy about 38% of the human genome. The calculations for noncoding genes are more complicated because there is considerable dispute over the total number of noncoding genes but taking only the well-defined examples means that noncoding genes occupy at least 6% of the genome.
=== Untranslated regions ===
The standard biochemistry and molecular biology textbooks describe non-coding nucleotides in mRNA located between the 5' end of the gene and the translation initiation codon. These regions are called 5'-untranslated regions or 5'-UTRs. Similar regions called 3'-untranslated regions (3'-UTRs) are found at the end of the gene. The 5'-UTRs and 3'UTRs are very short in bacteria but they can be several hundred nucleotides in length in eukaryotes. They contain short elements that control the initiation of translation (5'-UTRs) and transcription termination (3'-UTRs) as well as regulatory elements that may control mRNA stability, processing, and targeting to different regions of the cell.
=== Origins of replication ===
DNA synthesis begins at specific sites called origins of replication. These are regions of the genome where the DNA replication machinery is assembled and the DNA is unwound to begin DNA synthesis. In most cases, replication proceeds in both directions from the replication origin.
The main features of replication origins are sequences where specific initiation proteins are bound. A typical replication origin covers about 100-200 base pairs of DNA. Prokaryotes have one origin of replication per chromosome or plasmid but there are usually multiple origins in eukaryotic chromosomes. The human genome contains about 100,000 origins of replication representing about 0.3% of the genome.
=== Centromeres ===
Centromeres are the sites where spindle fibers attach to newly replicated chromosomes in order to segregate them into daughter cells when the cell divides. Each eukaryotic chromosome has a single functional centromere that is seen as a constricted region in a condensed metaphase chromosome. Centromeric DNA consists of a number of repetitive DNA sequences that often take up a significant fraction of the genome because each centromere can be millions of base pairs in length. In humans, for example, the sequences of all 24 centromeres have been determined and they account for about 6% of the genome. However, it is unlikely that all of this noncoding DNA is essential since there is considerable variation in the total amount of centromeric DNA in different individuals. Centromeres are another example of functional noncoding DNA sequences that have been known for almost half a century and it is likely that they are more abundant than coding DNA.
=== Telomeres ===
Telomeres are regions of repetitive DNA at the end of a chromosome, which provide protection from chromosomal deterioration during DNA replication. Recent studies have shown that telomeres function to aid in its own stability. Telomeric repeat-containing RNA (TERRA) are transcripts derived from telomeres. TERRA has been shown to maintain telomerase activity and lengthen the ends of chromosomes.
=== Scaffold attachment regions ===
Both prokaryotic and eukarotic genomes are organized into large loops of protein-bound DNA. In eukaryotes, the bases of the loops are called scaffold attachment regions (SARs) and they consist of stretches of DNA that bind an RNA/protein complex to stabilize the loop. There are about 100,000 loops in the human genome and each SAR consists of about 100 bp of DNA, so the total amount of DNA devoted to SARs accounts for about 0.3% of the human genome.
=== Pseudogenes ===
Pseudogenes are mostly former genes that have become non-functional due to mutation, but the term also refers to inactive DNA sequences that are derived from RNAs produced by functional genes (processed pseudogenes). Pseudogenes are only a small fraction of noncoding DNA in prokaryotic genomes because they are eliminated by negative selection. In some eukaryotes, however, pseudogenes can accumulate because selection is not powerful enough to eliminate them (see Nearly neutral theory of molecular evolution).
The human genome contains about 15,000 pseudogenes derived from protein-coding genes and an unknown number derived from noncoding genes. They may cover a substantial fraction of the genome (~5%) since many of them contain former intron sequences.
Pseudogenes are junk DNA by definition and they evolve at the neutral rate as expected for junk DNA. Some former pseudogenes have secondarily acquired a function and this leads some scientists to speculate that most pseudogenes are not junk because they have a yet-to-be-discovered function.
=== Repeat sequences, transposons and viral elements ===
Transposons and retrotransposons are mobile genetic elements. Retrotransposon repeated sequences, which include long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), account for a large proportion of the genomic sequences in many species. Alu sequences, classified as a short interspersed nuclear element, are the most abundant mobile elements in the human genome. Some examples have been found of SINEs exerting transcriptional control of some protein-encoding genes.
Endogenous retrovirus sequences are the product of reverse transcription of retrovirus genomes into the genomes of germ cells. Mutation within these retro-transcribed sequences can inactivate the viral genome.
Over 8% of the human genome is made up of (mostly decayed) endogenous retrovirus sequences, as part of the over 42% fraction that is recognizably derived of retrotransposons, while another 3% can be identified to be the remains of DNA transposons. Much of the remaining half of the genome that is currently without an explained origin is expected to have found its origin in transposable elements that were active so long ago (> 200 million years) that random mutations have rendered them unrecognizable. Genome size variation in at least two kinds of plants is mostly the result of retrotransposon sequences.
=== Highly repetitive DNA ===
Highly repetitive DNA consists of short stretches of DNA that are repeated many times in tandem (one after the other). The repeat segments are usually between 2 bp and 10 bp but longer ones are known. Highly repetitive DNA is rare in prokaryotes but common in eukaryotes, especially those with large genomes. It is sometimes called satellite DNA.
Most of the highly repetitive DNA is found in centromeres and telomeres (see above) and most of it is functional although some might be redundant. The other significant fraction resides in short tandem repeats (STRs; also called microsatellites) consisting of short stretches of a simple repeat such as ATC. There are about 350,000 STRs in the human genome and they are scattered throughout the genome with an average length of about 25 repeats.
Variations in the number of STR repeats can cause genetic diseases when they lie within a gene but most of these regions appear to be non-functional junk DNA where the number of repeats can vary considerably from individual to individual. This is why these length differences are used extensively in DNA fingerprinting.
=== Junk DNA ===
Junk DNA is DNA that has no biologically relevant function such as pseudogenes and fragments of once active transposons. Bacteria and viral genomes have very little junk DNA but some eukaryotic genomes may have a substantial amount of junk DNA. The exact amount of nonfunctional DNA in humans and other species with large genomes has not been determined and there is considerable controversy in the scientific literature.
The nonfunctional DNA in bacterial genomes is mostly located in the intergenic fraction of non-coding DNA but in eukaryotic genomes it may also be found within introns. There are many examples of functional DNA elements in non-coding DNA, and it is erroneous to equate non-coding DNA with junk DNA.
== Genome-wide association studies (GWAS) and non-coding DNA ==
Genome-wide association studies (GWAS) identify linkages between alleles and observable traits such as phenotypes and diseases. Most of the associations are between single-nucleotide polymorphisms (SNPs) and the trait being examined and most of these SNPs are located in non-functional DNA. The association establishes a linkage that helps map the DNA region responsible for the trait but it does not necessarily identify the mutations causing the disease or phenotypic difference.
SNPs that are tightly linked to traits are the ones most likely to identify a causal mutation. (The association is referred to as tight linkage disequilibrium.) About 12% of these polymorphisms are found in coding regions; about 40% are located in introns; and most of the rest are found in intergenic regions, including regulatory sequences.
== See also ==
Conserved non-coding sequence
Eukaryotic chromosome fine structure
Gene-centered view of evolution
Gene regulatory network
Intergenic region
Intragenomic conflict
Phylogenetic footprinting
Transcriptome
Non-coding RNA
Gene desert
The Onion Test
== References ==
== Further reading ==
== External links ==
Plant DNA C-values Database at Royal Botanic Gardens, Kew
Fungal Genome Size Database at Estonian Institute of Zoology and Botany
ENCODE: The human encyclopaedia at Nature ENCODE | Wikipedia/Noncoding_DNA |
A string-searching algorithm, sometimes called string-matching algorithm, is an algorithm that searches a body of text for portions that match by pattern.
A basic example of string searching is when the pattern and the searched text are arrays of elements of an alphabet (finite set) Σ. Σ may be a human language alphabet, for example, the letters A through Z and other applications may use a binary alphabet (Σ = {0,1}) or a DNA alphabet (Σ = {A,C,G,T}) in bioinformatics.
In practice, the method of feasible string-search algorithm may be affected by the string encoding. In particular, if a variable-width encoding is in use, then it may be slower to find the Nth character, perhaps requiring time proportional to N. This may significantly slow some search algorithms. One of many possible solutions is to search for the sequence of code units instead, but doing so may produce false matches unless the encoding is specifically designed to avoid it.
== Overview ==
The most basic case of string searching involves one (often very long) string, sometimes called the haystack, and one (often very short) string, sometimes called the needle. The goal is to find one or more occurrences of the needle within the haystack. For example, one might search for to within:
Some books are to be tasted, others to be swallowed, and some few to be chewed and digested.
One might request the first occurrence of "to", which is the fourth word; or all occurrences, of which there are 3; or the last, which is the fifth word from the end.
Very commonly, however, various constraints are added. For example, one might want to match the "needle" only where it consists of one (or more) complete words—perhaps defined as not having other letters immediately adjacent on either side. In that case a search for "hew" or "low" should fail for the example sentence above, even though those literal strings do occur.
Another common example involves "normalization". For many purposes, a search for a phrase such as "to be" should succeed even in places where there is something else intervening between the "to" and the "be":
More than one space
Other "whitespace" characters such as tabs, non-breaking spaces, line-breaks, etc.
Less commonly, a hyphen or soft hyphen
In structured texts, tags or even arbitrarily large but "parenthetical" things such as footnotes, list-numbers or other markers, embedded images, and so on.
Many symbol systems include characters that are synonymous (at least for some purposes):
Latin-based alphabets distinguish lower-case from upper-case, but for many purposes string search is expected to ignore the distinction.
Many languages include ligatures, where one composite character is equivalent to two or more other characters.
Many writing systems involve diacritical marks such as accents or vowel points, which may vary in their usage, or be of varying importance in matching.
DNA sequences can involve non-coding segments which may be ignored for some purposes, or polymorphisms that lead to no change in the encoded proteins, which may not count as a true difference for some other purposes.
Some languages have rules where a different character or form of character must be used at the start, middle, or end of words.
Finally, for strings that represent natural language, aspects of the language itself become involved. For example, one might wish to find all occurrences of a "word" despite it having alternate spellings, prefixes or suffixes, etc.
Another more complex type of search is regular expression searching, where the user constructs a pattern of characters or other symbols, and any match to the pattern should fulfill the search. For example, to catch both the American English word "color" and the British equivalent "colour", instead of searching for two different literal strings, one might use a regular expression such as:
colou?r
where the "?" conventionally makes the preceding character ("u") optional.
This article mainly discusses algorithms for the simpler kinds of string searching.
A similar problem introduced in the field of bioinformatics and genomics is the maximal exact matching (MEM). Given two strings, MEMs are common substrings that cannot be extended left or right without causing a mismatch.
== Examples of search algorithms ==
=== Naive string search ===
A simple and inefficient way to see where one string occurs inside another is to check at each index, one by one. First, we see if there is a copy of the needle starting at the first character of the haystack; if not, we look to see if there's a copy of the needle starting at the second character of the haystack, and so forth. In the normal case, we only have to look at one or two characters for each wrong position to see that it is a wrong position, so in the average case, this takes O(n + m) steps, where n is the length of the haystack and m is the length of the needle; but in the worst case, searching for a string like "aaaab" in a string like "aaaaaaaaab", it takes O(nm)
=== Finite-state-automaton-based search ===
In this approach, backtracking is avoided by constructing a deterministic finite automaton (DFA) that recognizes a stored search string. These are expensive to construct—they are usually created using the powerset construction—but are very quick to use. For example, the DFA shown to the right recognizes the word "MOMMY". This approach is frequently generalized in practice to search for arbitrary regular expressions.
=== Stubs ===
Knuth–Morris–Pratt computes a DFA that recognizes inputs with the string to search for as a suffix, Boyer–Moore starts searching from the end of the needle, so it can usually jump ahead a whole needle-length at each step. Baeza–Yates keeps track of whether the previous j characters were a prefix of the search string, and is therefore adaptable to fuzzy string searching. The bitap algorithm is an application of Baeza–Yates' approach.
=== Index methods ===
Faster search algorithms preprocess the text. After building a substring index, for example a suffix tree or suffix array, the occurrences of a pattern can be found quickly. As an example, a suffix tree can be built in
Θ
(
n
)
{\displaystyle \Theta (n)}
time, and all
z
{\displaystyle z}
occurrences of a pattern can be found in
O
(
m
)
{\displaystyle O(m)}
time under the assumption that the alphabet has a constant size and all inner nodes in the suffix tree know what leaves are underneath them. The latter can be accomplished by running a DFS algorithm from the root of the suffix tree.
=== Other variants ===
Some search methods, for instance trigram search, are intended to find a "closeness" score between the search string and the text rather than a "match/non-match". These are sometimes called "fuzzy" searches.
== Classification of search algorithms ==
=== Classification by a number of patterns ===
The various algorithms can be classified by the number of patterns each uses.
==== Single-pattern algorithms ====
In the following compilation, m is the length of the pattern, n the length of the searchable text, and k = |Σ| is the size of the alphabet.
1.^ Asymptotic times are expressed using O, Ω, and Θ notation.
2.^ Used to implement the memmem and strstr search functions in the glibc and musl C standard libraries.
3.^ Can be extended to handle approximate string matching and (potentially-infinite) sets of patterns represented as regular languages.
The Boyer–Moore string-search algorithm has been the standard benchmark for the practical string-search literature.
==== Algorithms using a finite set of patterns ====
In the following compilation, M is the length of the longest pattern, m their total length, n the length of the searchable text, o the number of occurrences.
==== Algorithms using an infinite number of patterns ====
Naturally, the patterns can not be enumerated finitely in this case. They are represented usually by a regular grammar or regular expression.
=== Classification by the use of preprocessing programs ===
Other classification approaches are possible. One of the most common uses preprocessing as main criteria.
=== Classification by matching strategies ===
Another one classifies the algorithms by their matching strategy:
Match the prefix first (Knuth–Morris–Pratt, Shift-And, Aho–Corasick)
Match the suffix first (Boyer–Moore and variants, Commentz-Walter)
Match the best factor first (BNDM, BOM, Set-BOM)
Other strategy (Naïve, Rabin–Karp, Vectorized)
== See also ==
Sequence alignment
Graph matching
Pattern matching
Compressed pattern matching
Matching wildcards
Full-text search
== References ==
R. S. Boyer and J. S. Moore, A fast string searching algorithm, Carom. ACM 20, (10), 262–272(1977).
Thomas H. Cormen, Charles E. Leiserson, Ronald L. Rivest, and Clifford Stein. Introduction to Algorithms, Third Edition. MIT Press and McGraw-Hill, 2009. ISBN 0-262-03293-7. Chapter 32: String Matching, pp. 985–1013.
== External links ==
Huge list of pattern matching links Last updated: 12/27/2008 20:18:38
Large (maintained) list of string-matching algorithms
NIST list of string-matching algorithms
StringSearch – high-performance pattern matching algorithms in Java – Implementations of many String-Matching-Algorithms in Java (BNDM, Boyer-Moore-Horspool, Boyer-Moore-Horspool-Raita, Shift-Or)
StringsAndChars – Implementations of many String-Matching-Algorithms (for single and multiple patterns) in Java
Exact String Matching Algorithms — Animation in Java, Detailed description and C implementation of many algorithms.
(PDF) Improved Single and Multiple Approximate String Matching Archived 2017-03-11 at the Wayback Machine
Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features
NyoTengu – high-performance pattern matching algorithm in C – Implementations of Vector and Scalar String-Matching-Algorithms in C | Wikipedia/String_searching_algorithm |
The Patterson function is used to solve the phase problem in X-ray crystallography. It was introduced in 1935 by Arthur Lindo Patterson while he was a visiting researcher in the laboratory of Bertram Eugene Warren at MIT.
The Patterson function is defined as
P
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{\displaystyle P(u,v,w)=\sum _{h,k,\ell \in \mathbb {Z} }\left|F_{h,k,\ell }\right|^{2}\;e^{-2\pi i(hu+kv+\ell w)}.}
It is essentially the Fourier transform of the intensities rather than the structure factors. The Patterson function is also equivalent to the electron density convolved with its inverse:
P
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{\displaystyle P\left({\vec {u}}\right)=\rho \left({\vec {r}}\right)*\rho \left(-{\vec {r}}\right).}
Furthermore, a Patterson map of N points will have N(N − 1) peaks, excluding the central (origin) peak and any overlap.
The peaks' positions in the Patterson function are the interatomic distance vectors and the peak heights are proportional to the product of the number of electrons in the atoms concerned.
Because for each vector between atoms i and j there is an oppositely oriented vector of the same length (between atoms j and i), the Patterson function always has centrosymmetry.
== One-dimensional example ==
Consider the series of delta functions given by
f
(
x
)
=
δ
(
x
)
+
3
δ
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x
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{\displaystyle f(x)=\delta (x)+3\delta (x-2)+\delta (x-5)+3\delta (x-8)+5\delta (x-10).\,}
The Patterson function is given by the following series of delta functions and unit step functions
P
(
u
)
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δ
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+
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δ
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{\displaystyle {\begin{aligned}P(u)={}&5\delta (u+10)+18\delta (u+8)+9\delta (u+6)+6\delta (u+5)+6\delta (u+3)\\&+18\delta (u+2)+45\delta (u)+18\delta (u-2)+6\delta (u-3)+6\delta (u-5)\\&+9\delta (u-6)+18\delta (u-8)+5\delta (u-10).\end{aligned}}}
== References ==
== External links ==
"Structural resolution. The Patterson function and the Patterson method". | Wikipedia/Patterson_function |
Triple-stranded DNA (also known as H-DNA or Triplex-DNA) is a DNA structure in which three oligonucleotides wind around each other and form a triple helix. In triple-stranded DNA, the third strand binds to a B-form DNA (via Watson–Crick base-pairing) double helix
by forming Hoogsteen base pairs or reversed Hoogsteen hydrogen bonds.
== Structure ==
Examples of triple-stranded DNA from natural sources with the necessary combination of base composition and structural elements have been described, for example in Satellite DNA.
=== Hoogsteen base pairing ===
A thymine (T) nucleobase can bind to a Watson–Crick base-pairing of T-A by forming a Hoogsteen hydrogen bond. The thymine hydrogen bonds with the adenosine (A) of the original double-stranded DNA to create a T-A*T base-triplet.
=== Intermolecular and intramolecular interactions ===
There are two classes of triplex DNA: intermolecular and intramolecular formations. An intermolecular triplex refers to triplex formation between a duplex and a different (third) strand of DNA. The third strand can either be from a neighboring chromosome or a triplex forming oligonucleotide (TFO). Intramolecular triplex DNA is formed from a duplex with homopurine and homopyrimidine strands with mirror repeat symmetry. The degree of supercoiling in DNA influences the amount of intramolecular triplex formation that occurs. There are two different types of intramolecular triplex DNA: H-DNA and H*-DNA. Formation of H-DNA is stabilized under acidic conditions and in the presence of divalent cations such as Mg2+. In this conformation, the homopyrimidine strand in the duplex bends back to bind to the purine strand in a parallel fashion. The base triads used to stabilize this conformation are T-A*T and C-G*A+. The cytosine of this base triad needs to be protonated in order to form this intramolecular triple helix, which is why this conformation is stabilized under acidic conditions. H*-DNA has favorable formation conditions at neutral pH and in the presence of divalent cations. This intramolecular conformation is formed from the binding of the homopurine and purine strand of the duplex in an antiparallel fashion. It is stabilized by T-A*A and C-G*G base triplets.
== Function ==
=== Triplex forming oligonucleotides (TFO) ===
TFOs are short (≈15-25 nt) nucleic acid strands that bind in the major groove of double-stranded DNA to form intramolecular triplex DNA structures. There is some evidence that they are also able to modulate gene activity in vivo. In peptide nucleic acid (PNA), the sugar-phosphate backbone of DNA is replaced with a protein-like backbone. PNAs form P-loops while interacting with duplex DNA, forming a triplex with one strand of DNA while displacing the other. Very unusual recombination or parallel triplexes, or R-DNA, have been assumed to form under RecA protein in the course of homologous recombination.
TFOs bind specifically to homopurine-homopyrimidine regions that are often common in promoter and intron sequences of genes, influencing cell signaling. TFOs can inhibit transcription by binding with high specificity to the DNA helix, thereby blocking the binding and function of transcription factors for particular sequences. By introducing TFOs into a cell (through transfection or other means), the expression of certain genes can be controlled. This application has novel implications in site-specific mutagenesis and gene therapy. In human prostate cancer cells, a transcription factor Ets2 is over-expressed and thought to drive forward the growth and survival of cells in such excess. Carbone et al. designed a sequence-specific TFO to the Ets2 promoter sequence that down-regulated the gene expression and led to a slowing of cell growth and cell death. Changxian et al. have also presented a TFO targeting the promoter sequence of bcl-2, a gene inhibiting apoptosis.
The observed inhibition of transcription can also have negative health effects like its role in the recessive, autosomal gene for Friedreich's Ataxia. In Fredrick's Ataxia, triplex DNA formation impairs the expression of intron 1 of the FXN gene. This results in the degeneration of the nervous system and spinal cord, impairing the movement of the limbs. To combat this triplex instability, nucleotide excision repair proteins (NERs) have been shown to recognize and repair triple-stranded DNA structures, reinstating full availability of the previously inhibited and unstable gene.
=== Peptide nucleic acids (PNA) ===
Peptide nucleic acids are synthetic oligonucleotides that resist protease degradation and are used to induce repair at site specific triplex formation regions on DNA genomic sites. PNAs are able to bind with high affinity and sequence specificity to a complementary DNA sequence through Watson-Crick base pairing binding and are able to form triple helices through parallel orientation Hoogsteen bonds with the PNA facing the 5’-end of the DNA strand. The PNA-DNA triplex are stable because PNAs consist of a neutrally charged pseudopeptide backbone which binds to the double stranded DNA (dsDNA) sequence. Similar to homopyrimidine in TFOs, homopyrimidine in PNAs are able to form a bond with the complementary homopurine in target sequence of the dsDNA. These DNA analogues are able to bind to dsDNA by exploiting ambient DNA conditions and different predicting modes of recognition. This is different from TFOs which bind though the major groove recognition of the dsDNA.
One of the predicting modes of recognition used for recognition is through a duplex invasion. Within mixed A–T/G–C dsDNA sequence is targeted by a pair of pseudo-complementary (pc) PNAs which are able to bind to dsDNAs via double invasion through the simultaneous formation of diaminopurine (D) and thiouracil (Us) which substitute for adenine and thymine, respectively. The pc PNA pair form a D-T and Us -A and G-C or C-G Watson-Crick paired PNA-DNA helix with each of complementary DNA strands. Another form of recognized duplex invasion at targeted sequence can occur in dsDNA containing mixed T–C sequences. This form of duplex invasion is achieved through a complementary sequence of homopurine PNA oligomers. This triplex is formed from a PNA-DNA hybrid that binds anti-parallel with the complementary DNA sequence and results in a displaced non-complementary DNA strand.
Additionally, PNA can be modified to form “clamp” triplex structures at the target site. One type of “clamp” formed is a bis-PNA structure, in which two PNA molecules are held together by a flexible linker such as 8-amino-3,6-dioxaoctanoic acid (O). The bis-PNA structure forms a PNA-DNA-PNA triplex at the target site, where one strand forms Watson-Crick base pairs with DNA in an antiparallel orientation and the other strand forms Hoogsteen base pairs with the homopurine DNA strand in the DNA-PNA duplex. A tail clamp PNA (tcPNA) is also another form of triplex clamp that can also be formed. TcPNAs contain an extended 5-10 bp tail that forms a PNA/DNA duplex in addition to a PNA-DNA-PNA “clamp”. This allows for more specified PNA binding without the need for a homopyrimidie/pyridine stretch. These clamp structures had been shown to have high affinity and specificity. The addition of lysine residues to either or both ends of PNA's could be used to increase cellular uptake and binding.
=== Genetic regulation ===
Triple-stranded DNA has been implicated in the regulation of several genes. For instance, the c-myc gene has been extensively mutated to examine the role that triplex DNA, versus the linear sequence, plays in gene regulation. A c-myc promoter element, termed the nuclease-sensitive element or NSE, can form tandem intramolecular triplexes of the H-DNA type and has a repetitive sequence motif (ACCCTCCCC)4. The mutated NSE was examined for transcriptional activity and for its intra- and intermolecular triplex-forming ability. The transcriptional activity of mutant NSEs can be predicted by the element's ability to form H-DNA and not by repeat number, position, or the number of mutant base pairs. DNA may therefore be a dynamic participant in the transcription of the c-myc gene.
==== Gene expression ====
According to several published articles, H-DNA has the ability to regulate gene expression depending on factors such as location and sequences in proximity. Although intergenic regions of the prokaryotic genome have shown low traces of naturally occurring H-DNA or triplex motifs, H-DNA structures have shown to be more prevalent in the eukaryotic genome. H-DNA has been shown to be especially abundant in mammalian cells including humans (1 in every 50,000 bp). Genetic sequences involved in gene regulation are typically found in the promoter regions of the eukaryotic genome.
Consequently, the promoter region has displayed the ability to form H-DNA with a higher frequency. A bioinformatic analysis of the S. cerevisiae genome observed the occurrence of H-DNA and other triplate DNA motifs in four organizational regions: introns, exons, promoter regions and miscellaneous regions. The bioinformatic displayed a total of 148 H-DNA or triplet DNA possible structures. The promoter region accounted for the higher frequency with 71 triplate structures, while the exons accounted for 57 triplate structures and the introns and miscellaneous accounted for 2 and 18 structures.
In vitro and in vivo studies of eukaryotic genome expression resulted in one of three results: up regulation, down regulation, or no change in the presence of H-DNA motifs. Kato et al. reported upregulation expression of lacZ, when H-DNA was introduced to the B-lactamase promoter. On the other hand, a similar study (Brachmachari et al.) reported no statistically significant inhibition of the lacZ reporter gene when H-DNA was inserted into the genome of mammalian COS cells. Although studies suggest regulation of H-DNA, the mechanism is still under investigation. Potaman et al. associates the mechanism of gene regulation to the interactions between the H-DNA and the TATA box found in the promoter region of Na,K-ATPase. In H-DNA formations adjacent to a TATA box, the H-DNA structure destabilizes the T-A bonds essential for transcription. The interference with the TATA box inhibits the transcriptional machinery and transcription initiation which interferes with gene expression. Other mechanisms associated with the genomic expression of a genetic sequence in the presence of H-DNA involves TFOs. In vitro studies have highlighted a decrease in gene expression in the presence of TFOs in mammalian cells. Another possible mechanism presented by Valentina et al. suggest the 13-mer AG motif oligonucleotide triplex complex (TFO complex) downregulates the transcription of mRNA through competitive inhibition. Direct inhibition of gene expression from H-DNA is key to mutagenesis, replication inhibition, and even DNA recombination in the genome.
==== Recombination ====
H-DNA motifs have been shown to stimulate homologous recombination with different mechanisms. Initial implications for the role of H-DNA in recombination came in the early 1990s when observing RecA, a bacterial DNA recombination protein composed of triple-helix DNA. RecA exhibits enzymatic activity essential for recombination. Homologous recombination involving H-DNA motifs have also been found in eukaryotes. RadA, a homologous protein to RecA, has been shown to have the same enzymatic activity in recombination as RecA. The protein has the ability to promote and exchange homologous strands through parallel triple stranded helices. The single stranded DNA (ssDNA) and complementary double stranded DNA (dsDNA) will form a D-loop structure. Another possible mechanism for RecA involves the ssDNA from two separate H-DNA structures to form Watson-Crick base pairs. The new structure is known as a Holliday junction, an intermediate in homologous recombination. H-DNA is also found in other forms of recombination. In mammalian cells, H-DNA-sequences displayed a high frequency of recombination. For example, a study conducted on myeloma cell line of mice found H-DNA structures in Cγ2a and Cγ2b, which participate in sister chromatid exchange.
== Biological implications ==
=== Genetic instability ===
Considerable research has been funneled into the biological implications relating to the presence of H-DNA in the major breakpoint regions (Mbr) and double-strand-breakpoints of certain genes. Recent work has linked the presence of non-B-DNA structures with cases of genetic instability.
Polypurine mirror-repeat H-DNA forming sequences were found neighboring the P1 promoter of the c-MYC gene and are associated with the major breakpoint hotspots of this region. Cases of genetic instability were also observed in the F1 offspring of transgenic mice after incorporation of human H-DNA-forming sequences paired with Z-DNA sequences into their genomes where no instability was previously reported. Additionally, formation of R.R.Y. H-DNA conformations have been observed at the Mbr of the bcl-2 gene. Formation of these structures has been posited to cause the t(14;18) translocation observed in many cancers and most follicular lymphomas. This observation has led to research that indicated a substantial decrease in translocation events can be observed after blocking the formation of H-DNA by altering the sequence of this region slightly. Long tracts of GAA·TTC have also been observed to form very stable H-DNA structures. Interactions between these two H-DNA structures, termed sticky DNA, has been shown to interrupt transcription of the X25, or frataxin gene. As decreased levels of the protein frataxin is associated with Friedreich's ataxia, formation of this instability has been suggested to be the basis for this genetic disease. Triple-stranded DNA has been observed in supercoiled Satellite DNA in regions where microsatellite copy numbers are highly variable, along with inverted-repeat Z-DNA structures within a larger 2.1kb satellite DNA repeat unit.
Additionally, H-DNA has been shown to cause mutations related to critical cellular processes like DNA replication and transcription. The importance of these processes for survival has led to the development of complex DNA repair mechanisms that allow cells to recognize and fix DNA damage. Non-canonical DNA structures can be perceived as damage by the cell, and recent work has shown an increased prevalence of mutations near non-B-DNA-forming sequences. Some of these mutations are due to the interactions between H-DNA and the enzymes involved in DNA replication and transcription, where H-DNA interferes with these processes and triggers various DNA repair mechanisms. This can cause genetic instability and implicates H-DNA in cancer formation.
==== DNA replication ====
DNA replication has been shown to affect the function of various DNA repair enzymes. H-DNA formation involves the formation of single-stranded DNA (ssDNA), which is more susceptible to attack by nucleases. Various nucleases have been shown to interact with H-DNA in a replication-dependent or replication-independent manner.
A study using human cells found that the nucleotide excision repair (NER) nucleases ERCC1-XPF and ERCC1-XPG induced genetic instability. These enzymes cleave H-DNA at the loop formed by the two Hoogsteen hydrogen-bonded strands and the 5' end of the other Watson-Crick hydrogen-bonded strand, respectively. This cleavage has been shown to induce large deletions that cause double strand breaks (DSBs) in DNA that can lead to genetic instability. In cells deficient in ERCC1-XPF and ERCC1-XPG, these deletions were less prevalent near H-DNA forming sequences. Additionally, more mutations were found in ERCC1-XPF and ERCC1-XPG deficient cells in the absence of DNA replication, which suggests they process H-DNA in a replication-independent manner.
Alternatively, the DNA-replication repair nuclease FEN1 was found to suppress genetic instability. Similar to ERCC1-XPG, FEN1 cleaves H-DNA at the 5' end of the strand not involved in Hoogsteen hydrogen-bonding. HeLa cells deficient in FEN1 showed higher prevalence of deletions near H-DNA forming sequences, but H-DNA induced mutagenesis was more pronounced in FEN1 deficient cells in the presence of DNA replication. This suggests FEN1 suppresses H-DNA-induced mutagenesis in a replication-dependent manner.
H-DNA has been implicated in human cancer etiology because of the prevalence of H-DNA-forming sequences near translocation breakpoints in cancer genomes. Replication-mediated nuclease activity with H-DNA highlights another way H-DNA-induced mutagenesis and lead to cancer growth.
==== Transcription ====
H-DNA forming sequences can also cause genetic instability by interfering with and stopping transcription prematurely. The DNA unwinding involved in transcription makes it more susceptible to damage. In transcription-coupled repair (TCR), a lesion on the template strand of DNA stops the function of RNA polymerase and signals TCR factors to resolve the damage by excising it. H-DNA can be perceived as one of these lesions.
A study observing transcription by T7 RNA polymerase on a stable H-DNA-forming sequence analog found transcription blockage at the duplex-to-triplex junction. Here, the template strand was the central strand of the H-DNA, and the difficulty of disrupting its Watson-Crick and Hoogsteen hydrogen bonds stopped transcription from progressing.
When transcription by T7 was observed on the P0 promoter of the c-MYC gene, the shortened transcription products that were found indicated that transcription was stopped in close proximity to the H-DNA forming sequence downstream of the promoter. Formation of H-DNA in this region prevents T7 from traveling down the template strand because of the steric hindrance it causes. This stops transcription and signals for TCR factors to come resolve the H-DNA, which results in DNA excision that can cause genetic instability. The mirror symmetry and prevalence of guanine residues in the c-MYC gene gives it a high propensity for non-canonical DNA structure formation. This coupled with the activity of TCR factors during transcription makes it highly mutagenic, with it playing a role in the development of Burkitt lymphoma and leukemia.
=== Applications ===
The triple-stranded DNA regions can be generated through the association of Triplex Forming Oligonucleotides (TFO) and Peptide Nucleic Acids (PNAs). Historically, TFO binding has been shown to inhibit transcription, replication, and protein binding to DNA. TFOs tethered to mutagens have also been shown to promote DNA damage and induce mutagenesis. Although TFO have been known to hinder transcription and replication of DNA, recent studies have shown that TFO can be utilized to mediate site specific gene modifications both in vitro and in vivo. Another recent study has also shown that TFOs can be used for suppression of oncogenes and proto-oncogenes to reduce cancer cell growth. For example, a recent study has used TFOs to reduce cellular death in hepatoma cells through the decreasing the expression of MET.
PNA TFOs have the ability to enhance recombination frequencies, leading to targeted, specific editing of genes. The PNA-DNA-PNA triplex helix is able to be recognized by the cell's own DNA repair mechanism, which sensitizes the surrounding DNA for homologous recombination. In order for a site-specific PNA structure to mediate recombination within a DNA sequence, a bis-PNA structure can be coupled with a 40nt DNA fragment that is homologous to an adjacent region on the target gene. The linking of a TFO to a donor DNA strand has been shown to induce recombination of the targeted gene and the adjacent gene target region. The mechanism for this form of recombination and repair have been linked to the nucleotide excision repair (NER) pathway playing a role in recognizing and repairing triplex structures. Multiple investigations suggests that the xeroderma pigmentosum group A (XPA) and replication protein A (RPA), which are NER factors, are able to bind specifically as a complex to cross-linked triplex structures. It is known that this mechanism alongside others play a role in recognizing and repairing triplex structures.
The in vivo delivery of TFOs has been a major barrier in using TFOs for gene modification. One study on in vivo targeting of hematopoietic stem cells proposed a novel technique of conjugating PNA molecules with cell penetrating peptide (CPPs) alongside poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enable 6 bp modifications in the CCR5 gene. The editing of the CCR5 gene has been linked to HIV-1 resistance. CPPs are proteins that are able to carry “cargo” such as small proteins or molecules successfully into cells. The PGLAs are biodegradable material that encapsulate PNA molecules as nanoparticles for site specific genome modifications. The study found that the PNA-DNA PGLA nanoparticles were able to effectively edit the hematopoietic stem cells with lower toxicity and virus-free and the conjugation with CPP offered direct targeting of the genes for site-specific mutagenesis in the stem cells.
In a novel study of cystic fibrosis (CF) gene therapy, three tail-clamp peptide nucleic acids (PNAs) alongside donor DNA molecule were engineered to be delivered by nanoparticles to correct F508 del mutations on the cystic fibrosis transmembrane conductance regulator (CFTR) in human bronchial epithelial cells in vivo and in vitro. The F508 del mutation is the most commonly occurring mutation which leads a person to have CF. The F508 mutation leads to a loss of function of the CFTR, which is a plasma membrane chloride channel that is regulated by a cyclic-adenosine monophosphate(cAMP). In this study, they were able to create the novel treatment approach for CF through the use of nanoparticles to correct the F508 del CFTR mutation both in vitro in human bronchial epithelial (HBE) cells and in vivo in a CF mouse model which resulted in the appearance of CFTR-dependent chloride transport.
== History ==
Triple-stranded DNA structures were common hypotheses in the 1950s when scientists were struggling to discover DNA's true structural form. Watson and Crick (who later won the Nobel Prize for their double-helix model) originally considered a triple-helix model, as did Pauling and Corey, who published a proposal for their triple-helix model in 1953, as well as fellow scientist Fraser. However, Watson and Crick soon identified several problems with these models:
Negatively charged phosphates near the axis repel each other, leaving the question of how the three-chain structure stays together.
In a triple-helix model (specifically Pauling and Corey's model), some of the van der Waals distances appear to be too small.
Fraser's model differed from Pauling and Corey's in that in his model the phosphates are on the outside and the bases are on the inside, linked together by hydrogen bonds. However, Watson and Crick found Fraser's model to be too ill-defined to comment specifically on its inadequacies.
An alternative triple-stranded DNA structure was described in 1957. Felsenfeld, Davies, and Rich predicted that if one strand contained only purines and the other strand only purines, the strand would undergo a conformational change to form a triple stranded DNA helix. The triple-stranded DNA (H-DNA) was predicted to be composed of one polypurine and two polypyrimidine strands. It was thought to occur in only one in vivo biological process: as an intermediate product during the action of the E. coli recombination enzyme RecA. Early models in the 1960s predicted the formation of complexes between polycetiylic and guanine oligonucleotides. The models suggested interactions known as Hoogsten pairing (non-Watson-Crick interactions) located in the major groove. Shortly after, triple helices composed of one pyrimidine and two purine strands were predicted. The discovery of in H-DNA stretches in supercoiled plasmids peaked modern interest in the potential function of triplex structures in living cells. Additionally, it was soon found that homopyrimidine and some purine-rich oligonucleotide are able form a stable H-DNA structure with the homopurine-homopyrimidine binding sequence-specific structures on the DNA duplexes.
== References ==
== Further reading == | Wikipedia/Triple-stranded_DNA |
Natural DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage.
DNA damage and mutation have different biological consequences. While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brains or muscles of adult mammals, and can cause aging. (Also see DNA damage theory of aging.) In replicating cells, such as cells lining the colon, errors occur upon replication of past damages in the template strand of DNA or during repair of DNA damages. These errors can give rise to mutations or epigenetic alterations. Both of these types of alteration can be replicated and passed on to subsequent cell generations. These alterations can change gene function or regulation of gene expression and possibly contribute to progression to cancer.
Throughout the cell cycle there are various checkpoints to ensure the cell is in good condition to progress to mitosis. The three main checkpoints are at G1/s, G2/m, and at the spindle assembly checkpoint regulating progression through anaphase. G1 and G2 checkpoints involve scanning for damaged DNA. During S phase the cell is more vulnerable to DNA damage than any other part of the cell cycle. G2 checkpoint checks for damaged DNA and DNA replication completeness.
== Types ==
Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes. Metabolism releases compounds that damage DNA including reactive oxygen species, reactive nitrogen species, reactive carbonyl species, lipid peroxidation products, and alkylating agents, among others, while hydrolysis cleaves chemical bonds in DNA. Naturally occurring oxidative DNA damages arise at least 10,000 times per cell per day in humans and as much as 100,000 per cell per day in rats as documented below.
Oxidative DNA damage can produce more than 20 types of altered bases as well as single strand breaks.
Other types of endogeneous DNA damages, given below with their frequencies of occurrence, include depurinations, depyrimidinations, double-strand breaks, O6-methylguanines, and cytosine deamination.
DNA can be damaged via environmental factors as well. Environmental agents such as UV light, ionizing radiation, and genotoxic chemicals. Replication forks can be stalled due to damaged DNA and double strand breaks are also a form of DNA damage.
=== Frequencies ===
The list below shows some frequencies with which new naturally occurring DNA damages arise per day, due to endogenous cellular processes.
Oxidative damages
Humans, per cell per day:
10,000
11,500
2,800 specific damages 8-oxoGua, 8-oxodG plus 5-HMUra
Rats, per cell per day:
74,000
86,000
100,000
Mice, per cell per day:
34,000 specific damages 8-oxoGua, 8-oxodG plus 5-HMUra
47,000 specific damages oxo8dG in mouse liver
28,000 specific damages 8-oxoGua, 8-oxodG, 5-HMUra
Depurinations
Mammalian cells, per cell per day:
2,000 to 10,000
9,000
12,000
13,920
Depyrimidinations
Mammalian cells, per cell per day:
600
696
Single-strand breaks
Mammalian cells, per cell per day:
55,200
Double-strand breaks
Human cells, per cell cycle
10
50
O6-methylguanines
Mammalian cells, per cell per day:
3,120
Cytosine deamination
Mammalian cells, per cell per day:
192
Another important endogenous DNA damage is M1dG, short for (3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrimido[1,2-a]-purin-10(3H)-one). The excretion in urine (likely reflecting rate of occurrence) of M1dG may be as much as 1,000-fold lower than that of 8-oxodG. However, a more important measure may be the steady-state level in DNA, reflecting both rate of occurrence and rate of DNA repair. The steady-state level of M1dG is higher than that of 8-oxodG. This points out that some DNA damages produced at a low rate may be difficult to repair and remain in DNA at a high steady-state level. Both M1dG and 8-oxodG are mutagenic.
=== Steady-state levels ===
Steady-state levels of DNA damages represent the balance between formation and repair. More than 100 types of oxidative DNA damage have been characterized, and 8-oxodG constitutes about 5% of the steady state oxidative damages in DNA. Helbock et al. estimated that there were 24,000 steady state oxidative DNA adducts per cell in young rats and 66,000 adducts per cell in old rats. This reflects the accumulation of DNA damage with age. DNA damage accumulation with age is further described in DNA damage theory of aging.
Swenberg et al. measured average amounts of selected steady state endogenous DNA damages in mammalian cells. The seven most common damages they evaluated are shown in Table 1.
Evaluating steady-state damages in specific tissues of the rat, Nakamura and Swenberg indicated that the number of abasic sites varied from about 50,000 per cell in liver, kidney and lung to about 200,000 per cell in the brain.
== Biomolecular pathways ==
Proteins promoting endogenous DNA damage were identified in a 2019 paper as the DNA "damage-up" proteins (DDPs). The DDP mechanisms fall into 3 clusters:
reactive oxygen increase by transmembrane transporters,
chromosome loss by replisome binding,
replication stalling by transcription factors.
The DDP human homologs are over-represented in known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis.
== Repair of damaged DNA ==
In the presence of DNA damage, the cell can either repair the damage or induce cell death if the damage is beyond repair.
=== Types ===
The seven main types of DNA repair and one pathway of damage tolerance, the lesions they address, and the accuracy of the repair (or tolerance) are shown in this table. For a brief description of the steps in repair see DNA repair mechanisms or see each individual pathway.
== Aging and cancer ==
The schematic diagram indicates the roles of insufficient DNA repair in aging and cancer, and the role of apoptosis in cancer prevention. An excess of naturally occurring DNA damage, due to inherited deficiencies in particular DNA repair enzymes, can cause premature aging or increased risk for cancer (see DNA repair-deficiency disorder). On the other hand, the ability to trigger apoptosis in the presence of excess un-repaired DNA damage is critical for prevention of cancer.
== Apoptosis and cancer prevention ==
DNA repair proteins are often activated or induced when DNA has sustained damage. However, excessive DNA damage can initiate apoptosis (i.e., programmed cell death) if the level of DNA damage exceeds the repair capacity. Apoptosis can prevent cells with excess DNA damage from undergoing mutagenesis and progression to cancer.
Inflammation is often caused by infection, such as with hepatitis B virus (HBV), hepatitis C virus (HCV) or Helicobacter pylori. Chronic inflammation is also a central characteristic of obesity. Such inflammation causes oxidative DNA damage. This is due to the induction of reactive oxygen species (ROS) by various intracellular inflammatory mediators. HBV and HCV infections, in particular, cause 10,000-fold and 100,000-fold increases in intracellular ROS production, respectively. Inflammation-induced ROS that cause DNA damage can trigger apoptosis, but may also cause cancer if repair and apoptotic processes are insufficiently protective.
Bile acids, stored in the gall bladder, are released into the small intestine in response to fat in the diet. Higher levels of fat cause greater release. Bile acids cause DNA damage, including oxidative DNA damage, double-strand DNA breaks, aneuploidy and chromosome breakage. High-normal levels of the bile acid deoxycholic acid cause apoptosis in human colon cells, but may also lead to colon cancer if repair and apoptotic defenses are insufficient.
Apoptosis serves as a safeguard mechanism against tumorigenesis. It prevents the increased mutagenesis that excess DNA damage could cause, upon replication.
At least 17 DNA repair proteins, distributed among five DNA repair pathways, have a "dual role" in response to DNA damage. With moderate levels of DNA damage, these proteins initiate or contribute to DNA repair. However, when excessive levels of DNA damage are present, they trigger apoptosis.
== DNA damage response ==
The packaging of eukaryotic DNA into chromatin is a barrier to all DNA-based processes that require enzyme action. For most DNA repair processes, the chromatin must be remodeled. In eukaryotes, ATP-dependent chromatin remodeling complexes and histone-modifying enzymes are two factors that act to accomplish this remodeling process after DNA damage occurs. Further DNA repair steps, involving multiple enzymes, usually follow. Some of the first responses to DNA damage, with their timing, are described below. More complete descriptions of the DNA repair pathways are presented in articles describing each pathway. At least 169 enzymes are involved in DNA repair pathways.
=== Base excision repair ===
Oxidized bases in DNA are produced in cells treated with Hoechst dye followed by micro-irradiation with 405 nm light. Such oxidized bases can be repaired by base excision repair.
When the 405 nm light is focused along a narrow line within the nucleus of a cell, about 2.5 seconds after irradiation, the chromatin remodeling enzyme Alc1 achieves half-maximum recruitment onto the irradiated micro-line. The line of chromatin that was irradiated then relaxes, expanding side-to-side over the next 60 seconds.
Within 6 seconds of the irradiation with 405 nm light, there is half-maximum recruitment of OGG1 to the irradiated line. OGG1 is an enzyme that removes the oxidative DNA damage 8-oxo-dG from DNA. Removal of 8-oxo-dG, during base excision repair, occurs with a half-life of 11 minutes.
=== Nucleotide excision repair ===
Ultraviolet (UV) light induces the formation of DNA damages including pyrimidine dimers (such as thymine dimers) and 6,4 photoproducts. These types of "bulky" damages are repaired by nucleotide excision repair.
After irradiation with UV light, DDB2, in a complex with DDB1, the ubiquitin ligase protein CUL4A and the RING finger protein ROC1, associates with sites of damage within chromatin. Half-maximum association occurs in 40 seconds. PARP1 also associates within this period. The PARP1 protein attaches to both DDB1 and DDB2 and then PARylates (creates a poly-ADP ribose chain) on DDB2 that attracts the DNA remodeling protein ALC1. ALC1 relaxes chromatin at sites of UV damage to DNA. In addition, the ubiquitin E3 ligase complex DDB1-CUL4A carries out ubiquitination of the core histones H2A, H3, and H4, as well as the repair protein XPC, which has been attracted to the site of the DNA damage. XPC, upon ubiquitination, is activated and initiates the nucleotide excision repair pathway. Somewhat later, at 30 minutes after UV damage, the INO80 chromatin remodeling complex is recruited to the site of the DNA damage, and this coincides with the binding of further nucleotide excision repair proteins, including ERCC1.
=== Homologous recombinational repair ===
Double-strand breaks (DSBs) at specific sites can be induced by transfecting cells with a plasmid encoding I-SceI endonuclease (a homing endonuclease). Multiple DSBs can be induced by irradiating sensitized cells (labeled with 5'-bromo-2'-deoxyuridine and with Hoechst dye) with 780 nm light. These DSBs can be repaired by the accurate homologous recombinational repair or by the less accurate non-homologous end joining repair pathway. Here we describe the early steps in homologous recombinational repair (HRR).
After treating cells to introduce DSBs, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites with half-maximum recruitment in well under a second. SIRT6 at the site is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to a DNA break site and for efficient repair of DSBs. PARP1 protein starts to appear at DSBs in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs. This then allows half maximum recruitment of the DNA repair enzymes MRE11 within 13 seconds and NBS1 within 28 seconds. MRE11 and NBS1 carry out early steps of the HRR pathway.
γH2AX, the phosphorylated form of H2AX is also involved in early steps of DSB repair. The histone variant H2AX constitutes about 10% of the H2A histones in human chromatin. γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute. The extent of chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break. γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation, RNF8 protein can be detected in association with γH2AX. RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with CHD4, a component of the nucleosome remodeling and deacetylase complex NuRD.
=== Pause for DNA repair ===
After rapid chromatin remodeling, cell cycle checkpoints may be activated to allow DNA repair to be completed before the cell cycle progresses. First, two kinases, ATM and ATR, are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation of the cell cycle checkpoint protein Chk1, initiating its function, about 10 minutes after DNA is damaged.
== Role of oxidative damage to guanine in gene regulation ==
The DNA damage 8-oxo-dG does not occur randomly in the genome. In mouse embryonic fibroblasts, a 2 to 5-fold enrichment of 8-oxo-dG was found in genetic control regions, including promoters, 5'-untranslated regions and 3'-untranslated regions compared to 8-oxo-dG levels found in gene bodies and in intergenic regions. In rat pulmonary artery endothelial cells, when 22,414 protein-coding genes were examined for locations of 8-oxo-dG, the majority of 8-oxo-dGs (when present) were found in promoter regions rather than within gene bodies. Among hundreds of genes whose expression levels were affected by hypoxia, those with newly acquired promoter 8-oxo-dGs were upregulated, and those genes whose promoters lost 8-oxo-dGs were almost all downregulated.
As reviewed by Wang et al., oxidized guanine appears to have multiple regulatory roles in gene expression. In particular, when oxidative stress produces 8-oxo-dG in the promoter of a gene, the oxidative stress may also inactivate OGG1, an enzyme that targets 8-oxo-dG and normally initiates repair of 8-oxo-dG damage. The inactive OGG1, which no longer excises 8-oxo-dG, nevertheless targets and complexes with 8-oxo-dG, and causes a sharp (~70o) bend in the DNA. This allows the assembly of a transcriptional initiation complex, up-regulating transcription of the associated gene.
When 8-oxo-dG is formed in a guanine rich, potential G-quadruplex-forming sequence (PQS) in the coding strand of a promoter, active OGG1 excises the 8-oxo-dG and generates an apurinic/apyrimidinic site (AP site). The AP site enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold (G4 structure/motif) that has a regulatory role in transcription activation.
When 8-oxo-dG is complexed with active OGG1 it may then recruit chromatin remodelers to modulate gene expression. Chromodomain helicase DNA-binding protein 4 (CHD4), a component of the (NuRD) complex, is recruited by OGG1 to oxidative DNA damage sites. CHD4 then attracts DNA and histone methylating enzymes that repress transcription of associated genes.
== Role of DNA damage in memory formation ==
=== Oxidation of guanine ===
Oxidation of guanine, particularly within CpG sites, may be especially important in learning and memory. Methylation of cytosines occurs at 60–90% of CpG sites depending on the tissue type. In the mammalian brain, ~62% of CpGs are methylated. Methylation of CpG sites tends to stably silence genes. More than 500 of these CpG sites are de-methylated in neuron DNA during memory formation and memory consolidation in the hippocampus and cingulate cortex regions of the brain. As indicated below, the first step in de-methylation of methylated cytosine at a CpG site is oxidation of the guanine to form 8-oxo-dG.
=== Role of oxidized guanine in DNA de-methylation ===
The figure in this section shows a CpG site where the cytosine is methylated to form 5-methylcytosine (5mC) and the guanine is oxidized to form 8-oxo-2'-deoxyguanosine (in the figure this is shown in the tautomeric form 8-OHdG). When this structure is formed, the base excision repair enzyme OGG1 targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits TET1, and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates de-methylation of 5mC. TET1 is a key enzyme involved in de-methylating 5mCpG. However, TET1 is only able to act on 5mCpG if the guanine was first oxidized to form 8-hydroxy-2'-deoxyguanosine (8-OHdG or its tautomer 8-oxo-dG), resulting in a 5mCp-8-OHdG dinucleotide (see figure in this section). This initiates the de-methylation pathway on the methylated cytosine, finally resulting in an unmethylated cytosine (see DNA oxidation for further steps in forming unmethylated cytosine).
Altered protein expression in neurons, due to changes in methylation of DNA, (likely controlled by 8-oxo-dG-dependent de-methylation of CpG sites in gene promoters within neuron DNA) has been established as central to memory formation.
=== Role of double-strand breaks in memory formation ===
==== Generation of neuronal activity-related DSBs ====
Double-stranded breaks (DSBs) in regions of DNA related to neuronal activity are produced by a variety of mechanisms within and around the genome. The enzyme topoisomerase II, or TOPIIβ plays a key role in DSB formation by aiding in the demethylation or loosening of histones wrapped around the double helix to promote transcription. Once the chromatin structure is opened, DSBs are more likely to accumulate, however, this is normally repaired by TOPIIβ through its intrinsic religation ability that rejoins the cleaved DNA ends.
Failure of TOPIIβ to religase can have drastic consequences on protein synthesis, where it is estimated that "blocking TOPIIβ activity alters the expression of nearly one-third of all developmentally regulated genes," such as neural immediate early genes (IEGs) involved in memory consolidation. Rapid expression of egr-1, c-Fos, and Arc IEGs have been observed in response to increased neuronal activity in the hippocampus region of the brain where memory processing takes place. As a preventative measure against TOPIIβ failure, DSB repair molecules are recruited via two different pathways: non-homologous end joining (NHEJ) pathway factors, which perform a similar religation function to that of TOPIIβ, and the homologous recombination (HR) pathway, which uses the non-broken sister strand as a template to repair the damaged strand of DNA.
Stimulation of neuronal activity, as previously mentioned in IEG expression, is another mechanism through which DSBs are generated. Changes in level of activity have been used in studies as a biomarker to trace the overlap between DSBs and increased histone H3K4 methylation in promoter regions of IEGs. Other studies have indicated that transposable elements (TEs) can cause DSBs through endogenous activity that involves using endonuclease enzymes to insert and cleave target DNA at random sites.
==== DSBs and memory reconsolidation ====
While accumulation of DSBs generally inhibits long-term memory consolidation, the process of memory reconsolidation, in contrast, is DSB-dependent. Memory reconsolidation involves the modification of existing memories stored in long-term memory. Research involving NPAS4, a gene that regulates neuroplasticity in the hippocampus during contextual learning and memory formation, has revealed a link between deletions in the coding region and impairments in recall of fear memories in transgenic rats. Moreover, the enzyme H3K4me3, which catalyzes the demethylation of the H3K4 histone, was upregulated at the promoter region of the NPAS4 gene during the reconsolidation process, while knockdown (gene knockdown) of the same enzyme impeded reconsolidation. A similar effect was observed in TOPIIβ, where knockdown also impaired the fear memory response in rats, indicating that DSBs, along with the enzymes that regulate them, influence memory formation at multiple stages.
==== DSBs and neurodegeneration ====
Buildup of DSBs more broadly leads to the degeneration of neurons, hindering the function of memory and learning processes. Due to their lack of cell division and high metabolic activity, neurons are especially prone to DNA damage. Additionally, an imbalance of DSBs and DNA repair molecules for neuronal-activity genes has been linked to the development of various human neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In patients with Alzheimer's disease, DSBs accumulate in neurons at early stages and are the driving force behind memory loss, a key characteristic of the disease. Other external factors that result in increased levels of activity-dependent DSBs in people with AD are oxidative damage to neurons, which can result in more DSBs when multiple lesions occur close to one another. Environmental factors such as viruses and a high-fat diet have also been associated with disrupted function of DNA repair molecules.
One targeted therapy for treating patients with AD has involved suppression of the BRCA1 gene in human brains, initially tested in transgenic mice, where DSB levels were observed to have increased and memory loss had occurred, suggesting that BRCA1 could "serve as a therapeutic target for AD and AD-related dementia." Similarly, the protein ATM involved in DNA repair and epigenetic modifications to the genome is positively correlated with neuronal loss in AD brains, indicating the protein is another key component in the intrinsically linked processes of neurodegeneration, DSB production, and memory formation.
== Role of ATR and ATM ==
Most damage can be repaired without triggering the damage response system, however more complex damage activates ATR and ATM, key protein kinases in the damage response system. DNA damage inhibits M-CDKs which are a key component of progression into mitosis.
In all eukaryotic cells, ATR and ATM are protein kinases that detect DNA damage. They bind to DNA damaged sites and activate Chk1, Chk2, and, in animal cells, p53. Together, these proteins make up the DNA damage response system. Some DNA damage does not require the recruitment of ATR and ATM, it is only difficult and extensive damage that requires ATR and ATM. ATM and ATR are required for NHEJ, HR, ICL repair, and NER, as well as replication fork stability during unperturbed DNA replication and in response to replication blocks.
ATR is recruited for different forms of damage such as nucleotide damage, stalled replication forks and double strand breaks. ATM is specifically for the damage response to double strand breaks. The MRN complex (composed of Mre11, Rad50, and Nbs1) form immediately at the site of double strand break. This MRN complex recruits ATM to the site of damage. ATR and ATM phosphorylate various proteins that contribute to the damage repair system. The binding of ATR and ATM to damage sites on DNA lead to the recruitment of Chk1 and Chk2. These protein kinases send damage signals to the cell cycle control system to delay the progression of the cell cycle.
== Chk1 and Chk2 functions ==
Chk1 leads to the production of DNA repair enzymes. Chk2 leads to reversible cell cycle arrest. Chk2, as well as ATR/ATM, can activate p53, which leads to permanent cell cycle arrest or apoptosis.
== p53 role in DNA damage repair system ==
When there is too much damage, apoptosis is triggered in order to protect the organism from potentially harmful cells.7 p53, also known as a tumor suppressor gene, is a major regulatory protein in the DNA damage response system which binds directly to the promoters of its target genes. p53 acts primarily at the G1 checkpoint (controlling the G1 to S transition), where it blocks cell cycle progression. Activation of p53 can trigger cell death or permanent cell cycle arrest. p53 can also activate certain repair pathways such was NER.
=== Regulation of p53 ===
In the absence of DNA damage, p53 is regulated by Mdm2 and constantly degraded. When there is DNA damage, Mdm2 is phosphorylated, most likely caused by ATM. The phosphorylation of Mdm2 leads to a reduction in the activity of Mdm2, thus preventing the degradation of p53. Normal, undamaged cell, usually has low levels of p53 while cells under stress and DNA damage, will have high levels of p53.
=== p53 serves as transcription factor for bax and p21 ===
p53 serves as a transcription factors for both bax, a proapoptotic protein as well as p21, a CDK inhibitor. CDK Inhibitors result in cell cycle arrest. Arresting the cell provides the cell time to repair the damage, and if the damage is irreparable, p53 recruits bax to trigger apoptosis.
=== DDR and p53 role in cancer ===
p53 is a major key player in the growth of cancerous cells. Damaged DNA cells with mutated p53 are at a higher risk of becoming cancerous. Common chemotherapy treatments are genotoxic. These treatments are ineffective in cancer tumor that have mutated p53 since they do not have a functioning p53 to either arrest or kill the damaged cell.
== A major problem for life ==
One indication that DNA damages are a major problem for life is that DNA repair processes, to cope with DNA damages, have been found in all cellular organisms in which DNA repair has been investigated. For example, in bacteria, a regulatory network aimed at repairing DNA damages (called the SOS response in Escherichia coli) has been found in many bacterial species. E. coli RecA, a key enzyme in the SOS response pathway, is the defining member of a ubiquitous class of DNA strand-exchange proteins that are essential for homologous recombination, a pathway that maintains genomic integrity by repairing broken DNA. Genes homologous to RecA and to other central genes in the SOS response pathway are found in almost all the bacterial genomes sequenced to date, covering a large number of phyla, suggesting both an ancient origin and a widespread occurrence of recombinational repair of DNA damage. Eukaryotic recombinases that are homologues of RecA are also widespread in eukaryotic organisms. For example, in fission yeast and humans, RecA homologues promote duplex-duplex DNA-strand exchange needed for repair of many types of DNA lesions.
Another indication that DNA damages are a major problem for life is that cells make large investments in DNA repair processes. As pointed out by Hoeijmakers, repairing just one double-strand break could require more than 10,000 ATP molecules, as used in signaling the presence of the damage, the generation of repair foci, and the formation (in humans) of the RAD51 nucleofilament (an intermediate in homologous recombinational repair). (RAD51 is a homologue of bacterial RecA.) If the structural modification occurs during the G1 phase of DNA replication, the G1-S checkpoint arrests or postpones the furtherance of the cell cycle before the product enters the S phase.
== Consequences ==
Differentiated somatic cells of adult mammals generally replicate infrequently or not at all. Such cells, including, for example, brain neurons and muscle myocytes, have little or no cell turnover. Non-replicating cells do not generally generate mutations due to DNA damage-induced errors of replication. These non-replicating cells do not commonly give rise to cancer, but they do accumulate DNA damages with time that likely contribute to aging (see DNA damage theory of aging). In a non-replicating cell, a single-strand break or other type of damage in the transcribed strand of DNA can block RNA polymerase II-catalysed transcription. This would interfere with the synthesis of the protein coded for by the gene in which the blockage occurred.
Brasnjevic et al. summarized the evidence showing that single-strand breaks accumulate with age in the brain (though accumulation differed in different regions of the brain) and that single-strand breaks are the most frequent steady-state DNA damages in the brain. As discussed above, these accumulated single-strand breaks would be expected to block transcription of genes. Consistent with this, as reviewed by Hetman et al., 182 genes were identified and shown to have reduced transcription in the brains of individuals older than 72 years, compared to transcription in the brains of those less than 43 years old. When 40 particular proteins were evaluated in a muscle of rats, the majority of the proteins showed significant decreases during aging from 18 months (mature rat) to 30 months (aged rat) of age.
Another type of DNA damage, the double-strand break, was shown to cause cell death (loss of cells) through apoptosis. This type of DNA damage would not accumulate with age, since once a cell was lost through apoptosis, its double-strand damage would be lost with it. Thus, damaged DNA segments undermine the DNA replication machinery because these altered sequences of DNA cannot be utilized as true templates to produce copies of one's genetic material.
== RAD genes and the cell cycle response to DNA damage in Saccharomyces cerevisiae ==
When DNA is damaged, the cell responds in various ways to fix the damage and minimize the effects on the cell. One such response, specifically in eukaryotic cells, is to delay cell division—the cell becomes arrested for some time in the G2 phase before progressing through the rest of the cell cycle. Various studies have been conducted to elucidate the purpose of this G2 arrest that is induced by DNA damage. Researchers have found that cells that are prematurely forced out of the delay have lower cell viability and higher rates of damaged chromosomes compared with cells that are able to undergo a full G2 arrest, suggesting that the purpose of the delay is to give the cell time to repair damaged chromosomes before continuing with the cell cycle. This ensures the proper functioning of mitosis.
Various species of animals exhibit similar mechanisms of cellular delay in response to DNA damage, which can be caused by exposure to x-irradiation. The budding yeast Saccharomyces cerevisiae has specifically been studied because progression through the cell cycle can be followed via nuclear morphology with ease. By studying Saccharomyces cerevisiae, researchers have been able to learn more about radiation-sensitive (RAD) genes, and the effect that RAD mutations may have on the typical cellular DNA damaged-induced delay response. Specifically, the RAD9 gene plays a crucial role in detecting DNA damage and arresting the cell in G2 until the damage is repaired.
Through extensive experiments, researchers have been able to illuminate the role that the RAD genes play in delaying cell division in response to DNA damage. When wild-type, growing cells are exposed to various levels of x-irradiation over a given time frame, and then analyzed with a microcolony assay, differences in the cell cycle response can be observed based on which genes are mutated in the cells. For instance, while unirradiated cells will progress normally through the cell cycle, cells that are exposed to x-irradiation either permanently arrest (become inviable) or delay in the G2 phase before continuing to divide in mitosis, further corroborating the idea that the G2 delay is crucial for DNA repair. However, rad strains, which are deficient in DNA repair, exhibit a markedly different response. For instance, rad52 cells, which cannot repair double-stranded DNA breaks, tend to permanently arrest in G2 when exposed to even very low levels of x-irradiation, and rarely end up progressing through the later stages of the cell cycle. This is because the cells cannot repair DNA damage and thus do not enter mitosis. Various other rad mutants exhibit similar responses when exposed to x-irradiation.
However, the rad9 strain exhibits an entirely different effect. These cells fail to delay in the G2 phase when exposed to x-irradiation, and end up progressing through the cell cycle unperturbed, before dying. This suggests that the RAD9 gene, unlike the other RAD genes, plays a crucial role in initiating G2 arrest. To further investigate these findings, the cell cycles of double mutant strains have been analyzed. A mutant rad52 rad9 strain—which is both defective in DNA repair and G2 arrest—fails to undergo cell cycle arrest when exposed to x-irradiation. This suggests that even if DNA damage cannot be repaired, if RAD9 is not present, the cell cycle will not delay. Thus, unrepaired DNA damage is the signal that tells RAD9 to halt division and arrest the cell cycle in G2. Furthermore, there is a dose-dependent response; as the levels of x-irradiation—and subsequent DNA damage—increase, more cells, regardless of the mutations they have, become arrested in G2.
Another, and perhaps more helpful way to visualize this effect is to look at photomicroscopy slides. Initially, slides of RAD+ and rad9 haploid cells in the exponential phase of growth show simple, single cells, that are indistinguishable from each other. However, the slides look much different after being exposed to x-irradiation for 10 hours. The RAD+ slides now show RAD+ cells existing primarily as two-budded microcolonies, suggesting that cell division has been arrested. In contrast, the rad9 slides show the rad9 cells existing primarily as 3 to 8 budded colonies, and they appear smaller than the RAD+ cells. This is further evidence that the mutant RAD cells continued to divide and are deficient in G2 arrest.
However, there is evidence that although the RAD9 gene is necessary to induce G2 arrest in response to DNA damage, giving the cell time to repair the damage, it does not actually play a direct role in repairing DNA. When rad9 cells are artificially arrested in G2 with MBC, a microtubule poison that prevents cellular division, and then treated with x-irradiation, the cells are able to repair their DNA and eventually progress through the cell cycle, dividing into viable cells. Thus, the RAD9 gene plays no role in actually repairing damaged DNA—it simply senses damaged DNA and responds by delaying cell division. The delay, then, is mediated by a control mechanism, rather than the physical damaged DNA.
On the other hand, it is possible that there are backup mechanisms that fill the role of RAD9 when it is not present. In fact, some studies have found that RAD9 does indeed play a critical role in DNA repair. In one study, rad9 mutant and normal cells in the exponential phase of growth were exposed to UV-irradiation and synchronized in specific phases of the cell cycle. After being incubated to permit DNA repair, the extent of pyrimidine dimerization (which is indicative of DNA damage) was assessed using sensitive primer extension techniques. It was found that the removal of DNA photolesions was much less efficient in rad9 mutant cells than normal cells, providing evidence that RAD9 is involved in DNA repair. Thus, the role of RAD9 in repairing DNA damage remains unclear.
Regardless, it is clear that RAD9 is necessary to sense DNA damage and halt cell division. RAD9 has been suggested to possess 3' to 5' exonuclease activity, which is perhaps why it plays a role in detecting DNA damage. When DNA is damaged, it is hypothesized that RAD9 forms a complex with RAD1 and HUS1, and this complex is recruited to sites of DNA damage. It is in this way that RAD9 is able to exert its effects.
Although the function of RAD9 has primarily been studied in the budding yeast Saccharomyces cerevisiae, many of the cell cycle control mechanisms are similar between species. Thus, we can conclude that RAD9 likely plays a critical role in the DNA damage response in humans as well.
== See also ==
== References == | Wikipedia/DNA_damage_(naturally_occurring) |
Hantaro Nagaoka (長岡 半太郎, Nagaoka Hantarō, August 19, 1865 – December 11, 1950) was a Japanese physicist and a pioneer of Japanese physics during the Meiji period.
== Life ==
Nagaoka was born in Nagasaki, Japan on August 19, 1865 and educated at the University of Tokyo.: 633 After graduating with a degree in physics in 1887, Nagaoka worked with a visiting Scottish physicist, Cargill Gilston Knott, on early problems in magnetism, namely magnetostriction in liquid nickel. In 1893, Nagaoka traveled to Europe, where he continued his education at the universities of Berlin, Munich, and Vienna, including courses on Saturn's rings and a course with Ludwig Boltzmann on his Kinetic Theory of Gases, two influences which would be reflected in Nagaoka's later work. Nagaoka also attended, in 1900, the first International Congress of Physics in Paris, where he heard Marie Curie lecture on radioactivity, an event that aroused Nagaoka's interest in atomic physics. Nagaoka returned to Japan in 1901 and served as professor of physics at Tokyo University until 1925. After his retirement from Tokyo University, Nagaoka was appointed a head scientist at RIKEN, and also served as the first president of Osaka University, from 1931 to 1934.
His granddaughter was pianist Nagaoka Nobuko.
== Saturnian model of the atom ==
By 1900 physicists had begun to consider new models for the structure of the atom. The recent discovery by J. J. Thomson of the negatively charged electron implied that a neutral atom must also contain an opposite positive charge. In 1904, Thomson suggested that the atom was a sphere of uniform positive electrification, with electrons scattered through it like plums in a pudding, giving rise to the term plum pudding model.
Nagaoka rejected Thomson's model on the grounds that opposite charges are impenetrable. In 1904, Nagaoka proposed an alternative planetary model of the atom in which a positively charged center is surrounded by a number of revolving electrons, in the manner of Saturn and its rings.
Nagaoka's model featured:
a very massive atomic center (in analogy to a very massive planet)
thousands of electrons revolving around the nucleus, bound by electrostatic forces (in analogy to the rings revolving around Saturn, bound by gravitational forces).
For his model to be stable, Nagaoka showed that the central charge had to be 10,000 times the charge on the electron.: 38
Based on his model, Nagaoka suggested that radioactive beta decay resulted from instability in the electron orbits. However this explanation did not account for important aspects of radioactivity such as its random nature and the high energy of alpha particle emission.: 343 He also suggested that the model would explain atomic spectra and chemical properties.: 38
Ernest Rutherford mentions Nagaoka's model in his 1911 paper in which the atomic nucleus is proposed. However Nagaoka's work probably did not influence Rutherford's proposal.
Nagaoka's model was widely discussed by prominent scientists of the day, but a detailed study by George Schott showed the model could not correctly predict atomic spectra.: 38
Nagaoka himself abandoned his proposed model in 1908.
Rutherford and Niels Bohr would present the more viable Bohr model in 1913.
== Other works ==
Nagaoka later did research in spectroscopy and other fields. In 1909, he published a paper on the inductance of solenoids. In 1924, he achieved the first successful synthesis of gold, produced from mercury by neutron bombardment. In 1929, Nagaoka became the first person to describe meteor burst communications.
Nagoka also did early research on earthquakes, from the 1900s to the 1920s, building upon works published Europe; "One used the principle of elasticity studies against the background of the current that succeeded in France in the first half of the 19th century. The other defined potential functions and explained phenomena from continuous equations of the nature of waves against the background of new currents that emerged in Britain or Germany from the mid-19th century onwards."
== Awards and recognition ==
For his lifetime of scientific work, Nagaoka was granted the Order of Culture by the Japanese government in 1937.
The Nagaoka crater on the Moon is named after him.
== References ==
== External links ==
H. Nagaoka
Historical Figures of RIKEN | Wikipedia/Saturnian_model |
In atomic physics, the Bohr model or Rutherford–Bohr model was a model of the atom that incorporated some early quantum concepts. Developed from 1911 to 1918 by Niels Bohr and building on Ernest Rutherford's nuclear model, it supplanted the plum pudding model of J. J. Thomson only to be replaced by the quantum atomic model in the 1920s. It consists of a small, dense nucleus surrounded by orbiting electrons. It is analogous to the structure of the Solar System, but with attraction provided by electrostatic force rather than gravity, and with the electron energies quantized (assuming only discrete values).
In the history of atomic physics, it followed, and ultimately replaced, several earlier models, including Joseph Larmor's Solar System model (1897), Jean Perrin's model (1901), the cubical model (1902), Hantaro Nagaoka's Saturnian model (1904), the plum pudding model (1904), Arthur Haas's quantum model (1910), the Rutherford model (1911), and John William Nicholson's nuclear quantum model (1912). The improvement over the 1911 Rutherford model mainly concerned the new quantum mechanical interpretation introduced by Haas and Nicholson, but forsaking any attempt to explain radiation according to classical physics.
The model's key success lies in explaining the Rydberg formula for hydrogen's spectral emission lines. While the Rydberg formula had been known experimentally, it did not gain a theoretical basis until the Bohr model was introduced. Not only did the Bohr model explain the reasons for the structure of the Rydberg formula, it also provided a justification for the fundamental physical constants that make up the formula's empirical results.
The Bohr model is a relatively primitive model of the hydrogen atom, compared to the valence shell model. As a theory, it can be derived as a first-order approximation of the hydrogen atom using the broader and much more accurate quantum mechanics and thus may be considered to be an obsolete scientific theory. However, because of its simplicity, and its correct results for selected systems (see below for application), the Bohr model is still commonly taught to introduce students to quantum mechanics or energy level diagrams before moving on to the more accurate, but more complex, valence shell atom. A related quantum model was proposed by Arthur Erich Haas in 1910 but was rejected until the 1911 Solvay Congress where it was thoroughly discussed. The quantum theory of the period between Planck's discovery of the quantum (1900) and the advent of a mature quantum mechanics (1925) is often referred to as the old quantum theory.
== Background ==
Until the second decade of the 20th century, atomic models were generally speculative. Even the concept of atoms, let alone atoms with internal structure, faced opposition from some scientists.: 2
=== Planetary models ===
In the late 1800s speculations on the possible structure of the atom included planetary models with orbiting charged electrons.: 35
These models faced a significant constraint.
In 1897, Joseph Larmor showed that an accelerating charge would radiate power according to classical electrodynamics, a result known as the Larmor formula. Since electrons forced to remain in orbit are continuously accelerating, they would be mechanically unstable. Larmor noted that electromagnetic effect of multiple electrons, suitable arranged, would cancel each other. Thus subsequent atomic models based on classical electrodynamics needed to adopt such special multi-electron arrangements.: 113
=== Thomson's atom model ===
When Bohr began his work on a new atomic theory in the summer of 1912: 237 the atomic model proposed by J. J. Thomson, now known as the plum pudding model, was the best available.: 37 Thomson proposed a model with electrons rotating in coplanar rings within an atomic-sized, positively-charged, spherical volume. Thomson showed that this model was mechanically stable by lengthy calculations and was electrodynamically stable under his original assumption of thousands of electrons per atom. Moreover, he suggested that the particularly stable configurations of electrons in rings was connected to chemical properties of the atoms. He developed a formula for the scattering of beta particles that seemed to match experimental results.: 38
However Thomson himself later showed that the atom had a factor of a thousand fewer electrons, challenging the stability argument and forcing the poorly understood positive sphere to have most of the atom's mass. Thomson was also unable to explain the many lines in atomic spectra.: 18
=== Rutherford nuclear model ===
In 1908, Hans Geiger and Ernest Marsden demonstrated that alpha particle occasionally scatter at large angles, a result inconsistent with Thomson's model.
In 1911 Ernest Rutherford developed a new scattering model, showing that the observed large angle scattering could be explained by a compact, highly charged mass at the center of the atom.
Rutherford scattering did not involve the electrons and thus his model of the atom was incomplete.
Bohr begins his first paper on his atomic model by describing Rutherford's atom as consisting of a small, dense, positively charged nucleus attracting negatively charged electrons.
=== Atomic spectra ===
By the early twentieth century, it was expected that the atom would account for the many atomic spectral lines. These lines were summarized in empirical formula by Johann Balmer and Johannes Rydberg. In 1897, Lord Rayleigh showed that vibrations of electrical systems predicted spectral lines that depend on the square of the vibrational frequency, contradicting the empirical formula which depended directly on the frequency.: 18
In 1907 Arthur W. Conway showed that, rather than the entire atom vibrating, vibrations of only one of the electrons in the system described by Thomson might be sufficient to account for spectral series.: II:106 Although Bohr's model would also rely on just the electron to explain the spectrum, he did not assume an electrodynamical model for the atom.
The other important advance in the understanding of atomic spectra was the Rydberg–Ritz combination principle which related atomic spectral line frequencies to differences between 'terms', special frequencies characteristic of each element.: 173 Bohr would recognize the terms as energy levels of the atom divided by the Planck constant, leading to the modern view that the spectral lines result from energy differences.: 847
=== Haas atomic model ===
In 1910, Arthur Erich Haas proposed a model of the hydrogen atom with an electron circulating on the surface of a sphere of positive charge. The model resembled Thomson's plum pudding model, but Haas added a radical new twist: he constrained the electron's potential energy,
E
pot
{\displaystyle E_{\text{pot}}}
, on a sphere of radius a to equal the frequency, f, of the electron's orbit on the sphere times the Planck constant:: 197
E
pot
=
−
e
2
a
=
h
f
{\displaystyle E_{\text{pot}}={\frac {-e^{2}}{a}}=hf}
where e represents the charge on the electron and the sphere. Haas combined this constraint with the balance-of-forces equation. The attractive force between the electron and the sphere balances the centrifugal force:
e
2
a
2
=
m
a
(
2
π
f
)
2
{\displaystyle {\frac {e^{2}}{a^{2}}}=ma(2\pi f)^{2}}
where m is the mass of the electron. This combination relates the radius of the sphere to the Planck constant:
a
=
h
2
4
π
2
e
2
m
{\displaystyle a={\frac {h^{2}}{4\pi ^{2}e^{2}m}}}
Haas solved for the Planck constant using the then-current value for the radius of the hydrogen atom.
Three years later, Bohr would use similar equations with different interpretation. Bohr took the Planck constant as given value and used the equations to predict, a, the radius of the electron orbiting in the ground state of the hydrogen atom. This value is now called the Bohr radius.: 197
=== Influence of the Solvay Conference ===
The first Solvay Conference, in 1911, was one of the first international physics conferences. Nine Nobel or future Nobel laureates attended, including
Ernest Rutherford, Bohr's mentor.: 271
Bohr did not attend but he read the Solvay reports and discussed them with Rutherford.: 233
The subject of the conference was the theory of radiation and the energy quanta of Max Planck's oscillators.
Planck's lecture at the conference ended with comments about atoms and the discussion that followed it concerned atomic models. Hendrik Lorentz raised the question of the composition of the atom based on Haas's model, a form of Thomson's plum pudding model with a quantum modification. Lorentz explained that the size of atoms could be taken to determine the Planck constant as Haas had done or the Planck constant could be taken as determining the size of atoms.: 273 Bohr would adopt the second path.
The discussions outlined the need for the quantum theory to be included in the atom. Planck explicitly mentions the failings of classical mechanics.: 273 While Bohr had already expressed a similar opinion in his PhD thesis, at Solvay the leading scientists of the day discussed a break with classical theories.: 244 Bohr's first paper on his atomic model cites the Solvay proceedings saying: "Whatever the alteration in the laws of motion of the electrons may be, it seems necessary to introduce in the laws in question a quantity foreign to the classical electrodynamics, i.e. Planck's constant, or as it often is called the elementary quantum of action." Encouraged by the Solvay discussions, Bohr would assume the atom was stable and abandon the efforts to stabilize classical models of the atom: 199
=== Nicholson atom theory ===
In 1911 John William Nicholson published a model of the atom which would influence Bohr's model. Nicholson developed his model based on the analysis of astrophysical spectroscopy. He connected the observed spectral line frequencies with the orbits of electrons in his atoms. The connection he adopted associated the atomic electron orbital angular momentum with the Planck constant.
Whereas Planck focused on a quantum of energy, Nicholson's angular momentum quantum relates to orbital frequency.
This new concept gave Planck constant an atomic meaning for the first time.: 169 In his 1913 paper Bohr cites Nicholson as finding quantized angular momentum important for the atom.
The other critical influence of Nicholson work was his detailed analysis of spectra. Before Nicholson's work Bohr thought the spectral data was not useful for understanding atoms. In comparing his work to Nicholson's, Bohr came to understand the spectral data and their value. When he then learned from a friend about Balmer's compact formula for the spectral line data, Bohr quickly realized his model would match it in detail.: 178
Nicholson's model was based on classical electrodynamics along the lines of J.J. Thomson's plum pudding model but his negative electrons orbiting a positive nucleus rather than circulating in a sphere. To avoid immediate collapse of this system he required that electrons come in pairs so the rotational acceleration of each electron was matched across the orbit.: 163 By 1913 Bohr had already shown, from the analysis of alpha particle energy loss, that hydrogen had only a single electron not a matched pair.: 195 Bohr's atomic model would abandon classical electrodynamics.
Nicholson's model of radiation was quantum but was attached to the orbits of the electrons. Bohr quantization would associate it with differences in energy levels of his model of hydrogen rather than the orbital frequency.
=== Bohr's previous work ===
Bohr completed his PhD in 1911 with a thesis 'Studies on the Electron Theory of Metals', an application of the classical electron theory of Hendrik Lorentz. Bohr noted two deficits of the classical model. The first concerned the specific heat of metals which James Clerk Maxwell noted in 1875: every additional degree of freedom in a theory of metals, like subatomic electrons, cause more disagreement with experiment. The second, the classical theory could not explain magnetism.: 194
After his PhD, Bohr worked briefly in the lab of JJ Thomson before moving to Rutherford's lab in Manchester to study radioactivity. He arrived just after Rutherford completed his proposal of a compact nuclear core for atoms. Charles Galton Darwin, also at Manchester, had just completed an analysis of alpha particle energy loss in metals, concluding the electron collisions where the dominant cause of loss. Bohr showed in a subsequent paper that Darwin's results would improve by accounting for electron binding energy. Importantly this allowed Bohr to conclude that hydrogen atoms have a single electron.: 195
== Development ==
Next, Bohr was told by his friend, Hans Hansen, that the Balmer series is calculated using the Balmer formula, an empirical equation discovered by Johann Balmer in 1885 that described wavelengths of some spectral lines of hydrogen. This was further generalized by Johannes Rydberg in 1888, resulting in what is now known as the Rydberg formula.
After this, Bohr declared, "everything became clear".
In 1913 Niels Bohr put forth three postulates to provide an electron model consistent with Rutherford's nuclear model:
The electron is able to revolve in certain stable orbits around the nucleus without radiating any energy, contrary to what classical electromagnetism suggests. These stable orbits are called stationary orbits and are attained at certain discrete distances from the nucleus. The electron cannot have any other orbit in between the discrete ones.
The stationary orbits are attained at distances for which the angular momentum of the revolving electron is an integer multiple of the reduced Planck constant:
m
e
v
r
=
n
ℏ
{\displaystyle m_{\mathrm {e} }vr=n\hbar }
, where
n
=
1
,
2
,
3
,
.
.
.
{\displaystyle n=1,2,3,...}
is called the principal quantum number, and
ℏ
=
h
/
2
π
{\displaystyle \hbar =h/2\pi }
. The lowest value of
n
{\displaystyle n}
is 1; this gives the smallest possible orbital radius, known as the Bohr radius, of 0.0529 nm for hydrogen. Once an electron is in this lowest orbit, it can get no closer to the nucleus. Starting from the angular momentum quantum rule as Bohr admits is previously given by Nicholson in his 1912 paper, Bohr was able to calculate the energies of the allowed orbits of the hydrogen atom and other hydrogen-like atoms and ions. These orbits are associated with definite energies and are also called energy shells or energy levels. In these orbits, the electron's acceleration does not result in radiation and energy loss. The Bohr model of an atom was based upon Planck's quantum theory of radiation.
Electrons can only gain and lose energy by jumping from one allowed orbit to another, absorbing or emitting electromagnetic radiation with a frequency
ν
{\displaystyle \nu }
determined by the energy difference of the levels according to the Planck relation:
Δ
E
=
E
2
−
E
1
=
h
ν
{\displaystyle \Delta E=E_{2}-E_{1}=h\nu }
, where
h
{\displaystyle h}
is the Planck constant.
Other points are:
Like Einstein's theory of the photoelectric effect, Bohr's formula assumes that during a quantum jump a discrete amount of energy is radiated. However, unlike Einstein, Bohr stuck to the classical Maxwell theory of the electromagnetic field. Quantization of the electromagnetic field was explained by the discreteness of the atomic energy levels; Bohr did not believe in the existence of photons.
According to the Maxwell theory the frequency
ν
{\displaystyle \nu }
of classical radiation is equal to the rotation frequency
ν
{\displaystyle \nu }
rot of the electron in its orbit, with harmonics at integer multiples of this frequency. This result is obtained from the Bohr model for jumps between energy levels
E
n
{\displaystyle E_{n}}
and
E
n
−
k
{\displaystyle E_{n-k}}
when
k
{\displaystyle k}
is much smaller than
n
{\displaystyle n}
. These jumps reproduce the frequency of the
k
{\displaystyle k}
-th harmonic of orbit
n
{\displaystyle n}
. For sufficiently large values of
n
{\displaystyle n}
(so-called Rydberg states), the two orbits involved in the emission process have nearly the same rotation frequency, so that the classical orbital frequency is not ambiguous. But for small
n
{\displaystyle n}
(or large
k
{\displaystyle k}
), the radiation frequency has no unambiguous classical interpretation. This marks the birth of the correspondence principle, requiring quantum theory to agree with the classical theory only in the limit of large quantum numbers.
The Bohr–Kramers–Slater theory (BKS theory) is a failed attempt to extend the Bohr model, which violates the conservation of energy and momentum in quantum jumps, with the conservation laws only holding on average.
Bohr's condition, that the angular momentum be an integer multiple of
ℏ
{\displaystyle \hbar }
, was later reinterpreted in 1924 by de Broglie as a standing wave condition: the electron is described by a wave and a whole number of wavelengths must fit along the circumference of the electron's orbit:
n
λ
=
2
π
r
.
{\displaystyle n\lambda =2\pi r.}
According to de Broglie's hypothesis, matter particles such as the electron behave as waves. The de Broglie wavelength of an electron is
λ
=
h
m
v
,
{\displaystyle \lambda ={\frac {h}{mv}},}
which implies that
n
h
m
v
=
2
π
r
,
{\displaystyle {\frac {nh}{mv}}=2\pi r,}
or
n
h
2
π
=
m
v
r
,
{\displaystyle {\frac {nh}{2\pi }}=mvr,}
where
m
v
r
{\displaystyle mvr}
is the angular momentum of the orbiting electron. Writing
ℓ
{\displaystyle \ell }
for this angular momentum, the previous equation becomes
ℓ
=
n
h
2
π
,
{\displaystyle \ell ={\frac {nh}{2\pi }},}
which is Bohr's second postulate.
Bohr described angular momentum of the electron orbit as
2
/
h
{\displaystyle 2/h}
while de Broglie's wavelength of
λ
=
h
/
p
{\displaystyle \lambda =h/p}
described
h
{\displaystyle h}
divided by the electron momentum. In 1913, however, Bohr justified his rule by appealing to the correspondence principle, without providing any sort of wave interpretation. In 1913, the wave behavior of matter particles such as the electron was not suspected.
In 1925, a new kind of mechanics was proposed, quantum mechanics, in which Bohr's model of electrons traveling in quantized orbits was extended into a more accurate model of electron motion. The new theory was proposed by Werner Heisenberg. Another form of the same theory, wave mechanics, was discovered by the Austrian physicist Erwin Schrödinger independently, and by different reasoning. Schrödinger employed de Broglie's matter waves, but sought wave solutions of a three-dimensional wave equation describing electrons that were constrained to move about the nucleus of a hydrogen-like atom, by being trapped by the potential of the positive nuclear charge.
== Electron energy levels ==
The Bohr model gives almost exact results only for a system where two charged points orbit each other at speeds much less than that of light. This not only involves one-electron systems such as the hydrogen atom, singly ionized helium, and doubly ionized lithium, but it includes positronium and Rydberg states of any atom where one electron is far away from everything else. It can be used for K-line X-ray transition calculations if other assumptions are added (see Moseley's law below). In high energy physics, it can be used to calculate the masses of heavy quark mesons.
Calculation of the orbits requires two assumptions.
Classical mechanics
The electron is held in a circular orbit by electrostatic attraction. The centripetal force is equal to the Coulomb force.
m
e
v
2
r
=
Z
k
e
e
2
r
2
,
{\displaystyle {\frac {m_{\mathrm {e} }v^{2}}{r}}={\frac {Zk_{\mathrm {e} }e^{2}}{r^{2}}},}
where me is the electron's mass, e is the elementary charge, ke is the Coulomb constant and Z is the atom's atomic number. It is assumed here that the mass of the nucleus is much larger than the electron mass (which is a good assumption). This equation determines the electron's speed at any radius:
v
=
Z
k
e
e
2
m
e
r
.
{\displaystyle v={\sqrt {\frac {Zk_{\mathrm {e} }e^{2}}{m_{\mathrm {e} }r}}}.}
It also determines the electron's total energy at any radius:
E
=
−
1
2
m
e
v
2
.
{\displaystyle E=-{\frac {1}{2}}m_{\mathrm {e} }v^{2}.}
The total energy is negative and inversely proportional to r. This means that it takes energy to pull the orbiting electron away from the proton. For infinite values of r, the energy is zero, corresponding to a motionless electron infinitely far from the proton. The total energy is half the potential energy, the difference being the kinetic energy of the electron. This is also true for noncircular orbits by the virial theorem.
A quantum rule
The angular momentum L = mevr is an integer multiple of ħ:
m
e
v
r
=
n
ℏ
.
{\displaystyle m_{\mathrm {e} }vr=n\hbar .}
=== Derivation ===
In classical mechanics, if an electron is orbiting around an atom with period T, and if its coupling to the electromagnetic field is weak, so that the orbit doesn't decay very much in one cycle, it will emit electromagnetic radiation in a pattern repeating at every period, so that the Fourier transform of the pattern will only have frequencies which are multiples of 1/T.
However, in quantum mechanics, the quantization of angular momentum leads to discrete energy levels of the orbits, and the emitted frequencies are quantized according to the energy differences between these levels. This discrete nature of energy levels introduces a fundamental departure from the classical radiation law, giving rise to distinct spectral lines in the emitted radiation.
Bohr assumes that the electron is circling the nucleus in an elliptical orbit obeying the rules of classical mechanics, but with no loss of radiation due to the Larmor formula.
Denoting the total energy as E, the electron charge as −e, the nucleus charge as K = Ze, the electron mass as me, half the major axis of the ellipse as a, he starts with these equations:: 3
E is assumed to be negative, because a positive energy is required to unbind the electron from the nucleus and put it at rest at an infinite distance.
Eq. (1a) is obtained from equating the centripetal force to the Coulombian force acting between the nucleus and the electron, considering that
E
=
T
+
U
{\displaystyle E=T+U}
(where T is the average kinetic energy and U the average electrostatic potential), and that for Kepler's second law, the average separation between the electron and the nucleus is a.
Eq. (1b) is obtained from the same premises of eq. (1a) plus the virial theorem, stating that, for an elliptical orbit,
Then Bohr assumes that
|
E
|
{\displaystyle \vert E\vert }
is an integer multiple of the energy of a quantum of light with half the frequency of the electron's revolution frequency,: 4 i.e.:
From eq. (1a, 1b, 2), it descends:
He further assumes that the orbit is circular, i.e.
a
=
r
{\displaystyle a=r}
, and, denoting the angular momentum of the electron as L, introduces the equation:
Eq. (4) stems from the virial theorem, and from the classical mechanics relationships between the angular momentum, the kinetic energy and the frequency of revolution.
From eq. (1c, 2, 4), it stems:
where:
that is:
This results states that the angular momentum of the electron is an integer multiple of the reduced Planck constant.: 15
Substituting the expression for the velocity gives an equation for r in terms of n:
m
e
k
e
Z
e
2
m
e
r
r
=
n
ℏ
,
{\displaystyle m_{\text{e}}{\sqrt {\dfrac {k_{\text{e}}Ze^{2}}{m_{\text{e}}r}}}r=n\hbar ,}
so that the allowed orbit radius at any n is
r
n
=
n
2
ℏ
2
Z
k
e
e
2
m
e
.
{\displaystyle r_{n}={\frac {n^{2}\hbar ^{2}}{Zk_{\mathrm {e} }e^{2}m_{\mathrm {e} }}}.}
The smallest possible value of r in the hydrogen atom (Z = 1) is called the Bohr radius and is equal to:
r
1
=
ℏ
2
k
e
e
2
m
e
≈
5.29
×
10
−
11
m
=
52.9
p
m
.
{\displaystyle r_{1}={\frac {\hbar ^{2}}{k_{\mathrm {e} }e^{2}m_{\mathrm {e} }}}\approx 5.29\times 10^{-11}~\mathrm {m} =52.9~\mathrm {pm} .}
The energy of the n-th level for any atom is determined by the radius and quantum number:
E
=
−
Z
k
e
e
2
2
r
n
=
−
Z
2
(
k
e
e
2
)
2
m
e
2
ℏ
2
n
2
≈
−
13.6
Z
2
n
2
e
V
.
{\displaystyle E=-{\frac {Zk_{\mathrm {e} }e^{2}}{2r_{n}}}=-{\frac {Z^{2}(k_{\mathrm {e} }e^{2})^{2}m_{\mathrm {e} }}{2\hbar ^{2}n^{2}}}\approx {\frac {-13.6\ Z^{2}}{n^{2}}}~\mathrm {eV} .}
An electron in the lowest energy level of hydrogen (n = 1) therefore has about 13.6 eV less energy than a motionless electron infinitely far from the nucleus. The next energy level (n = 2) is −3.4 eV. The third (n = 3) is −1.51 eV, and so on. For larger values of n, these are also the binding energies of a highly excited atom with one electron in a large circular orbit around the rest of the atom. The hydrogen formula also coincides with the Wallis product.
The combination of natural constants in the energy formula is called the Rydberg energy (RE):
R
E
=
(
k
e
e
2
)
2
m
e
2
ℏ
2
.
{\displaystyle R_{\mathrm {E} }={\frac {(k_{\mathrm {e} }e^{2})^{2}m_{\mathrm {e} }}{2\hbar ^{2}}}.}
This expression is clarified by interpreting it in combinations that form more natural units:
m
e
c
2
{\displaystyle m_{\mathrm {e} }c^{2}}
is the rest mass energy of the electron (511 keV),
k
e
e
2
ℏ
c
=
α
≈
1
137
{\displaystyle {\frac {k_{\mathrm {e} }e^{2}}{\hbar c}}=\alpha \approx {\frac {1}{137}}}
is the fine-structure constant,
R
E
=
1
2
(
m
e
c
2
)
α
2
{\displaystyle R_{\mathrm {E} }={\frac {1}{2}}(m_{\mathrm {e} }c^{2})\alpha ^{2}}
.
Since this derivation is with the assumption that the nucleus is orbited by one electron, we can generalize this result by letting the nucleus have a charge q = Ze, where Z is the atomic number. This will now give us energy levels for hydrogenic (hydrogen-like) atoms, which can serve as a rough order-of-magnitude approximation of the actual energy levels. So for nuclei with Z protons, the energy levels are (to a rough approximation):
E
n
=
−
Z
2
R
E
n
2
.
{\displaystyle E_{n}=-{\frac {Z^{2}R_{\mathrm {E} }}{n^{2}}}.}
The actual energy levels cannot be solved analytically for more than one electron (see n-body problem) because the electrons are not only affected by the nucleus but also interact with each other via the Coulomb force.
When Z = 1/α (Z ≈ 137), the motion becomes highly relativistic, and Z2 cancels the α2 in R; the orbit energy begins to be comparable to rest energy. Sufficiently large nuclei, if they were stable, would reduce their charge by creating a bound electron from the vacuum, ejecting the positron to infinity. This is the theoretical phenomenon of electromagnetic charge screening which predicts a maximum nuclear charge. Emission of such positrons has been observed in the collisions of heavy ions to create temporary super-heavy nuclei.
The Bohr formula properly uses the reduced mass of electron and proton in all situations, instead of the mass of the electron,
m
red
=
m
e
m
p
m
e
+
m
p
=
m
e
1
1
+
m
e
/
m
p
.
{\displaystyle m_{\text{red}}={\frac {m_{\mathrm {e} }m_{\mathrm {p} }}{m_{\mathrm {e} }+m_{\mathrm {p} }}}=m_{\mathrm {e} }{\frac {1}{1+m_{\mathrm {e} }/m_{\mathrm {p} }}}.}
However, these numbers are very nearly the same, due to the much larger mass of the proton, about 1836.1 times the mass of the electron, so that the reduced mass in the system is the mass of the electron multiplied by the constant 1836.1/(1 + 1836.1) = 0.99946. This fact was historically important in convincing Rutherford of the importance of Bohr's model, for it explained the fact that the frequencies of lines in the spectra for singly ionized helium do not differ from those of hydrogen by a factor of exactly 4, but rather by 4 times the ratio of the reduced mass for the hydrogen vs. the helium systems, which was much closer to the experimental ratio than exactly 4.
For positronium, the formula uses the reduced mass also, but in this case, it is exactly the electron mass divided by 2. For any value of the radius, the electron and the positron are each moving at half the speed around their common center of mass, and each has only one fourth the kinetic energy. The total kinetic energy is half what it would be for a single electron moving around a heavy nucleus.
E
n
=
R
E
2
n
2
{\displaystyle E_{n}={\frac {R_{\mathrm {E} }}{2n^{2}}}}
(positronium).
== Rydberg formula ==
Beginning in late 1860s, Johann Balmer and later Johannes Rydberg and Walther Ritz developed increasingly accurate empirical formula matching measured atomic spectral lines.
Critical for Bohr's later work, Rydberg expressed his formula in terms of wave-number, equivalent to frequency. These formula contained a constant,
R
{\displaystyle R}
, now known the Rydberg constant and a pair of integers indexing the lines:: 247
ν
=
R
(
1
m
2
−
1
n
2
)
.
{\displaystyle \nu =R\left({\frac {1}{m^{2}}}-{\frac {1}{n^{2}}}\right).}
Despite many attempts, no theory of the atom could reproduce these relatively simple formula.: 169
In Bohr's theory describing the energies of transitions or quantum jumps between orbital energy levels is able to explain these formula. For the hydrogen atom Bohr starts with his derived formula for the energy released as a free electron moves into a stable circular orbit indexed by
τ
{\displaystyle \tau }
:
W
τ
=
2
π
2
m
e
4
h
2
τ
2
{\displaystyle W_{\tau }={\frac {2\pi ^{2}me^{4}}{h^{2}\tau ^{2}}}}
The energy difference between two such levels is then:
h
ν
=
W
τ
2
−
W
τ
1
=
2
π
2
m
e
4
h
2
(
1
τ
2
2
−
1
τ
1
2
)
{\displaystyle h\nu =W_{\tau _{2}}-W_{\tau _{1}}={\frac {2\pi ^{2}me^{4}}{h^{2}}}\left({\frac {1}{\tau _{2}^{2}}}-{\frac {1}{\tau _{1}^{2}}}\right)}
Therefore, Bohr's theory gives the Rydberg formula and moreover the numerical value the Rydberg constant for hydrogen in terms of more fundamental constants of nature, including the electron's charge, the electron's mass, and the Planck constant:: 31
c
R
H
=
2
π
2
m
e
4
h
3
.
{\displaystyle cR_{\text{H}}={\frac {2\pi ^{2}me^{4}}{h^{3}}}.}
Since the energy of a photon is
E
=
h
c
λ
,
{\displaystyle E={\frac {hc}{\lambda }},}
these results can be expressed in terms of the wavelength of the photon given off:
1
λ
=
R
(
1
n
f
2
−
1
n
i
2
)
.
{\displaystyle {\frac {1}{\lambda }}=R\left({\frac {1}{n_{\text{f}}^{2}}}-{\frac {1}{n_{\text{i}}^{2}}}\right).}
Bohr's derivation of the Rydberg constant, as well as the concomitant agreement of Bohr's formula with experimentally observed spectral lines of the Lyman (nf = 1), Balmer (nf = 2), and Paschen (nf = 3) series, and successful theoretical prediction of other lines not yet observed, was one reason that his model was immediately accepted.: 34
To apply to atoms with more than one electron, the Rydberg formula can be modified by replacing Z with Z − b or n with n − b where b is constant representing a screening effect due to the inner-shell and other electrons (see Electron shell and the later discussion of the "Shell Model of the Atom" below). This was established empirically before Bohr presented his model.
== Shell model (heavier atoms) ==
Bohr's original three papers in 1913 described mainly the electron configuration in lighter elements. Bohr called his electron shells, "rings" in 1913. Atomic orbitals within shells did not exist at the time of his planetary model. Bohr explains in Part 3 of his famous 1913 paper that the maximum electrons in a shell is eight, writing: "We see, further, that a ring of n electrons cannot rotate in a single ring round a nucleus of charge ne unless n < 8." For smaller atoms, the electron shells would be filled as follows: "rings of electrons will only join together if they contain equal numbers of electrons; and that accordingly the numbers of electrons on inner rings will only be 2, 4, 8". However, in larger atoms the innermost shell would contain eight electrons, "on the other hand, the periodic system of the elements strongly suggests that already in neon N = 10 an inner ring of eight electrons will occur". Bohr wrote "From the above we are led to the following possible scheme for the arrangement of the electrons in light atoms:"
In Bohr's third 1913 paper Part III called "Systems Containing Several Nuclei", he says that two atoms form molecules on a symmetrical plane and he reverts to describing hydrogen. The 1913 Bohr model did not discuss higher elements in detail and John William Nicholson was one of the first to prove in 1914 that it couldn't work for lithium, but was an attractive theory for hydrogen and ionized helium.
In 1921, following the work of chemists and others involved in work on the periodic table, Bohr extended the model of hydrogen to give an approximate model for heavier atoms. This gave a physical picture that reproduced many known atomic properties for the first time although these properties were proposed contemporarily with the identical work of chemist Charles Rugeley Bury
Bohr's partner in research during 1914 to 1916 was Walther Kossel who corrected Bohr's work to show that electrons interacted through the outer rings, and Kossel called the rings: "shells". Irving Langmuir is credited with the first viable arrangement of electrons in shells with only two in the first shell and going up to eight in the next according to the octet rule of 1904, although Kossel had already predicted a maximum of eight per shell in 1916. Heavier atoms have more protons in the nucleus, and more electrons to cancel the charge. Bohr took from these chemists the idea that each discrete orbit could only hold a certain number of electrons. Per Kossel, after that the orbit is full, the next level would have to be used. This gives the atom a shell structure designed by Kossel, Langmuir, and Bury, in which each shell corresponds to a Bohr orbit.
This model is even more approximate than the model of hydrogen, because it treats the electrons in each shell as non-interacting. But the repulsions of electrons are taken into account somewhat by the phenomenon of screening. The electrons in outer orbits do not only orbit the nucleus, but they also move around the inner electrons, so the effective charge Z that they feel is reduced by the number of the electrons in the inner orbit.
For example, the lithium atom has two electrons in the lowest 1s orbit, and these orbit at Z = 2. Each one sees the nuclear charge of Z = 3 minus the screening effect of the other, which crudely reduces the nuclear charge by 1 unit. This means that the innermost electrons orbit at approximately 1/2 the Bohr radius. The outermost electron in lithium orbits at roughly the Bohr radius, since the two inner electrons reduce the nuclear charge by 2. This outer electron should be at nearly one Bohr radius from the nucleus. Because the electrons strongly repel each other, the effective charge description is very approximate; the effective charge Z doesn't usually come out to be an integer.
The shell model was able to qualitatively explain many of the mysterious properties of atoms which became codified in the late 19th century in the periodic table of the elements. One property was the size of atoms, which could be determined approximately by measuring the viscosity of gases and density of pure crystalline solids. Atoms tend to get smaller toward the right in the periodic table, and become much larger at the next line of the table. Atoms to the right of the table tend to gain electrons, while atoms to the left tend to lose them. Every element on the last column of the table is chemically inert (noble gas).
In the shell model, this phenomenon is explained by shell-filling. Successive atoms become smaller because they are filling orbits of the same size, until the orbit is full, at which point the next atom in the table has a loosely bound outer electron, causing it to expand. The first Bohr orbit is filled when it has two electrons, which explains why helium is inert. The second orbit allows eight electrons, and when it is full the atom is neon, again inert. The third orbital contains eight again, except that in the more correct Sommerfeld treatment (reproduced in modern quantum mechanics) there are extra "d" electrons. The third orbit may hold an extra 10 d electrons, but these positions are not filled until a few more orbitals from the next level are filled (filling the n = 3 d-orbitals produces the 10 transition elements). The irregular filling pattern is an effect of interactions between electrons, which are not taken into account in either the Bohr or Sommerfeld models and which are difficult to calculate even in the modern treatment.
== Moseley's law and calculation (K-alpha X-ray emission lines) ==
Niels Bohr said in 1962: "You see actually the Rutherford work was not taken seriously. We cannot understand today, but it was not taken seriously at all. There was no mention of it any place. The great change came from Moseley."
In 1913, Henry Moseley found an empirical relationship between the strongest X-ray line emitted by atoms under electron bombardment (then known as the K-alpha line), and their atomic number Z. Moseley's empiric formula was found to be derivable from Rydberg's formula and later Bohr's formula (Moseley actually mentions only Ernest Rutherford and Antonius Van den Broek in terms of models as these had been published before Moseley's work and Moseley's 1913 paper was published the same month as the first Bohr model paper). The two additional assumptions that [1] this X-ray line came from a transition between energy levels with quantum numbers 1 and 2, and [2], that the atomic number Z when used in the formula for atoms heavier than hydrogen, should be diminished by 1, to (Z − 1)2.
Moseley wrote to Bohr, puzzled about his results, but Bohr was not able to help. At that time, he thought that the postulated innermost "K" shell of electrons should have at least four electrons, not the two which would have neatly explained the result. So Moseley published his results without a theoretical explanation.
It was Walther Kossel in 1914 and in 1916 who explained that in the periodic table new elements would be created as electrons were added to the outer shell. In Kossel's paper, he writes: "This leads to the conclusion that the electrons, which are added further, should be put into concentric rings or shells, on each of which ... only a certain number of electrons—namely, eight in our case—should be arranged. As soon as one ring or shell is completed, a new one has to be started for the next element; the number of electrons, which are most easily accessible, and lie at the outermost periphery, increases again from element to element and, therefore, in the formation of each new shell the chemical periodicity is repeated." Later, chemist Langmuir realized that the effect was caused by charge screening, with an inner shell containing only 2 electrons. In his 1919 paper, Irving Langmuir postulated the existence of "cells" which could each only contain two electrons each, and these were arranged in "equidistant layers".
In the Moseley experiment, one of the innermost electrons in the atom is knocked out, leaving a vacancy in the lowest Bohr orbit, which contains a single remaining electron. This vacancy is then filled by an electron from the next orbit, which has n=2. But the n=2 electrons see an effective charge of Z − 1, which is the value appropriate for the charge of the nucleus, when a single electron remains in the lowest Bohr orbit to screen the nuclear charge +Z, and lower it by −1 (due to the electron's negative charge screening the nuclear positive charge). The energy gained by an electron dropping from the second shell to the first gives Moseley's law for K-alpha lines,
E
=
h
ν
=
E
i
−
E
f
=
R
E
(
Z
−
1
)
2
(
1
1
2
−
1
2
2
)
,
{\displaystyle E=h\nu =E_{i}-E_{f}=R_{\mathrm {E} }(Z-1)^{2}\left({\frac {1}{1^{2}}}-{\frac {1}{2^{2}}}\right),}
or
f
=
ν
=
R
v
(
3
4
)
(
Z
−
1
)
2
=
(
2.46
×
10
15
Hz
)
(
Z
−
1
)
2
.
{\displaystyle f=\nu =R_{\mathrm {v} }\left({\frac {3}{4}}\right)(Z-1)^{2}=(2.46\times 10^{15}~{\text{Hz}})(Z-1)^{2}.}
Here, Rv = RE/h is the Rydberg constant, in terms of frequency equal to 3.28×1015 Hz. For values of Z between 11 and 31 this latter relationship had been empirically derived by Moseley, in a simple (linear) plot of the square root of X-ray frequency against atomic number (however, for silver, Z = 47, the experimentally obtained screening term should be replaced by 0.4). Notwithstanding its restricted validity, Moseley's law not only established the objective meaning of atomic number, but as Bohr noted, it also did more than the Rydberg derivation to establish the validity of the Rutherford/Van den Broek/Bohr nuclear model of the atom, with atomic number (place on the periodic table) standing for whole units of nuclear charge. Van den Broek had published his model in January 1913 showing the periodic table was arranged according to charge while Bohr's atomic model was not published until July 1913.
The K-alpha line of Moseley's time is now known to be a pair of close lines, written as (Kα1 and Kα2) in Siegbahn notation.
== Shortcomings ==
The Bohr model gives an incorrect value L=ħ for the ground state orbital angular momentum: The angular momentum in the true ground state is known to be zero from experiment. Although mental pictures fail somewhat at these levels of scale, an electron in the lowest modern "orbital" with no orbital momentum, may be thought of as not to revolve "around" the nucleus at all, but merely to go tightly around it in an ellipse with zero area (this may be pictured as "back and forth", without striking or interacting with the nucleus). This is only reproduced in a more sophisticated semiclassical treatment like Sommerfeld's. Still, even the most sophisticated semiclassical model fails to explain the fact that the lowest energy state is spherically symmetric – it doesn't point in any particular direction.
In modern quantum mechanics, the electron in hydrogen is a spherical cloud of probability that grows denser near the nucleus. The rate-constant of probability-decay in hydrogen is equal to the inverse of the Bohr radius, but since Bohr worked with circular orbits, not zero area ellipses, the fact that these two numbers exactly agree is considered a "coincidence". (However, many such coincidental agreements are found between the semiclassical vs. full quantum mechanical treatment of the atom; these include identical energy levels in the hydrogen atom and the derivation of a fine-structure constant, which arises from the relativistic Bohr–Sommerfeld model (see below) and which happens to be equal to an entirely different concept, in full modern quantum mechanics).
The Bohr model also failed to explain:
Much of the spectra of larger atoms. At best, it can make predictions about the K-alpha and some L-alpha X-ray emission spectra for larger atoms, if two additional ad hoc assumptions are made. Emission spectra for atoms with a single outer-shell electron (atoms in the lithium group) can also be approximately predicted. Also, if the empiric electron–nuclear screening factors for many atoms are known, many other spectral lines can be deduced from the information, in similar atoms of differing elements, via the Ritz–Rydberg combination principles (see Rydberg formula). All these techniques essentially make use of Bohr's Newtonian energy-potential picture of the atom.
The relative intensities of spectral lines; although in some simple cases, Bohr's formula or modifications of it, was able to provide reasonable estimates (for example, calculations by Kramers for the Stark effect).
The existence of fine structure and hyperfine structure in spectral lines, which are known to be due to a variety of relativistic and subtle effects, as well as complications from electron spin.
The Zeeman effect – changes in spectral lines due to external magnetic fields; these are also due to more complicated quantum principles interacting with electron spin and orbital magnetic fields.
Doublets and triplets appear in the spectra of some atoms as very close pairs of lines. Bohr's model cannot say why some energy levels should be very close together.
Multi-electron atoms do not have energy levels predicted by the model. It does not work for (neutral) helium.
== Refinements ==
Several enhancements to the Bohr model were proposed, most notably the Sommerfeld or Bohr–Sommerfeld models, which suggested that electrons travel in elliptical orbits around a nucleus instead of the Bohr model's circular orbits. This model supplemented the quantized angular momentum condition of the Bohr model with an additional radial quantization condition, the Wilson–Sommerfeld quantization condition
∫
0
T
p
r
d
q
r
=
n
h
,
{\displaystyle \int _{0}^{T}p_{\text{r}}\,dq_{\text{r}}=nh,}
where pr is the radial momentum canonically conjugate to the coordinate qr, which is the radial position, and T is one full orbital period. The integral is the action of action-angle coordinates. This condition, suggested by the correspondence principle, is the only one possible, since the quantum numbers are adiabatic invariants.
The Bohr–Sommerfeld model was fundamentally inconsistent and led to many paradoxes. The magnetic quantum number measured the tilt of the orbital plane relative to the xy plane, and it could only take a few discrete values. This contradicted the obvious fact that an atom could have any orientation relative to the coordinates, without restriction. The Sommerfeld quantization can be performed in different canonical coordinates and sometimes gives different answers. The incorporation of radiation corrections was difficult, because it required finding action-angle coordinates for a combined radiation/atom system, which is difficult when the radiation is allowed to escape. The whole theory did not extend to non-integrable motions, which meant that many systems could not be treated even in principle. In the end, the model was replaced by the modern quantum-mechanical treatment of the hydrogen atom, which was first given by Wolfgang Pauli in 1925, using Heisenberg's matrix mechanics. The current picture of the hydrogen atom is based on the atomic orbitals of wave mechanics, which Erwin Schrödinger developed in 1926.
However, this is not to say that the Bohr–Sommerfeld model was without its successes. Calculations based on the Bohr–Sommerfeld model were able to accurately explain a number of more complex atomic spectral effects. For example, up to first-order perturbations, the Bohr model and quantum mechanics make the same predictions for the spectral line splitting in the Stark effect. At higher-order perturbations, however, the Bohr model and quantum mechanics differ, and measurements of the Stark effect under high field strengths helped confirm the correctness of quantum mechanics over the Bohr model. The prevailing theory behind this difference lies in the shapes of the orbitals of the electrons, which vary according to the energy state of the electron.
The Bohr–Sommerfeld quantization conditions lead to questions in modern mathematics. Consistent semiclassical quantization condition requires a certain type of structure on the phase space, which places topological limitations on the types of symplectic manifolds which can be quantized. In particular, the symplectic form should be the curvature form of a connection of a Hermitian line bundle, which is called a prequantization.
Bohr also updated his model in 1922, assuming that certain numbers of electrons (for example, 2, 8, and 18) correspond to stable "closed shells".
== Model of the chemical bond ==
Niels Bohr proposed a model of the atom and a model of the chemical bond. According to his model for a diatomic molecule, the electrons of the atoms of the molecule form a rotating ring whose plane is perpendicular to the axis of the molecule and equidistant from the atomic nuclei. The dynamic equilibrium of the molecular system is achieved through the balance of forces between the forces of attraction of nuclei to the plane of the ring of electrons and the forces of mutual repulsion of the nuclei. The Bohr model of the chemical bond took into account the Coulomb repulsion – the electrons in the ring are at the maximum distance from each other.
== Symbolism of planetary atomic models ==
Although Bohr's atomic model was superseded by quantum models in the 1920s, the visual image of electrons orbiting a nucleus has remained the popular concept of atoms.
The concept of an atom as a tiny planetary system has been widely used as a symbol for atoms and even for "atomic" energy (even though this is more properly considered nuclear energy).: 58 Examples of its use over the past century include but are not limited to:
The logo of the United States Atomic Energy Commission, which was in part responsible for its later usage in relation to nuclear fission technology in particular.
The flag of the International Atomic Energy Agency is a "crest-and-spinning-atom emblem", enclosed in olive branches.
The US minor league baseball Albuquerque Isotopes' logo shows baseballs as electrons orbiting a large letter "A".
A similar symbol, the atomic whirl, was chosen as the symbol for the American Atheists, and has come to be used as a symbol of atheism in general.
The Unicode Miscellaneous Symbols code point U+269B (⚛) for an atom looks like a planetary atom model.
The television show The Big Bang Theory uses a planetary-like image in its print logo.
The JavaScript library React uses planetary-like image as its logo.
On maps, it is generally used to indicate a nuclear power installation.
== See also ==
== References ==
=== Footnotes ===
=== Primary sources ===
Bohr, N. (July 1913). "I. On the constitution of atoms and molecules". The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science. 26 (151): 1–25. Bibcode:1913PMag...26....1B. doi:10.1080/14786441308634955.
Bohr, N. (September 1913). "XXXVII. On the constitution of atoms and molecules". The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science. 26 (153): 476–502. Bibcode:1913PMag...26..476B. doi:10.1080/14786441308634993.
Bohr, N. (1 November 1913). "LXXIII. On the constitution of atoms and molecules". The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science. 26 (155): 857–875. Bibcode:1913PMag...26..857B. doi:10.1080/14786441308635031.
Bohr, N. (October 1913). "The Spectra of Helium and Hydrogen". Nature. 92 (2295): 231–232. Bibcode:1913Natur..92..231B. doi:10.1038/092231d0. S2CID 11988018.
Bohr, N. (March 1921). "Atomic Structure". Nature. 107 (2682): 104–107. Bibcode:1921Natur.107..104B. doi:10.1038/107104a0. S2CID 4035652.
A. Einstein (1917). "Zum Quantensatz von Sommerfeld und Epstein". Verhandlungen der Deutschen Physikalischen Gesellschaft. 19: 82–92. Reprinted in The Collected Papers of Albert Einstein, A. Engel translator, (1997) Princeton University Press, Princeton. 6 p. 434. (provides an elegant reformulation of the Bohr–Sommerfeld quantization conditions, as well as an important insight into the quantization of non-integrable (chaotic) dynamical systems.)
de Broglie, Maurice; Langevin, Paul; Solvay, Ernest; Einstein, Albert (1912). La théorie du rayonnement et les quanta : rapports et discussions de la réunion tenue à Bruxelles, du 30 octobre au 3 novembre 1911, sous les auspices de M.E. Solvay (in French). Gauthier-Villars. OCLC 1048217622.
== Further reading ==
Linus Carl Pauling (1970). "Chapter 5-1". General Chemistry (3rd ed.). San Francisco: W.H. Freeman & Co.
Reprint: Linus Pauling (1988). General Chemistry. New York: Dover Publications. ISBN 0-486-65622-5.
George Gamow (1985). "Chapter 2". Thirty Years That Shook Physics. Dover Publications.
Walter J. Lehmann (1972). "Chapter 18". Atomic and Molecular Structure: the development of our concepts. John Wiley and Sons. ISBN 0-471-52440-9.
Paul Tipler and Ralph Llewellyn (2002). Modern Physics (4th ed.). W. H. Freeman. ISBN 0-7167-4345-0.
Klaus Hentschel: Elektronenbahnen, Quantensprünge und Spektren, in: Charlotte Bigg & Jochen Hennig (eds.) Atombilder. Ikonografien des Atoms in Wissenschaft und Öffentlichkeit des 20. Jahrhunderts, Göttingen: Wallstein-Verlag 2009, pp. 51–61
Steven and Susan Zumdahl (2010). "Chapter 7.4". Chemistry (8th ed.). Brooks/Cole. ISBN 978-0-495-82992-8.
Kragh, Helge (November 2011). "Conceptual objections to the Bohr atomic theory — do electrons have a 'free will'?". The European Physical Journal H. 36 (3): 327–352. Bibcode:2011EPJH...36..327K. doi:10.1140/epjh/e2011-20031-x. S2CID 120859582.
== External links ==
Standing waves in Bohr's atomic model—An interactive simulation to intuitively explain the quantization condition of standing waves in Bohr's atomic mode | Wikipedia/Rutherford–Bohr_model |
Matrix mechanics is a formulation of quantum mechanics created by Werner Heisenberg, Max Born, and Pascual Jordan in 1925. It was the first conceptually autonomous and logically consistent formulation of quantum mechanics. Its account of quantum jumps supplanted the Bohr model's electron orbits. It did so by interpreting the physical properties of particles as matrices that evolve in time. It is equivalent to the Schrödinger wave formulation of quantum mechanics, as manifest in Dirac's bra–ket notation.
In some contrast to the wave formulation, it produces spectra of (mostly energy) operators by purely algebraic, ladder operator methods. Relying on these methods, Wolfgang Pauli derived the hydrogen atom spectrum in 1926, before the development of wave mechanics.
== Development of matrix mechanics ==
In 1925, Werner Heisenberg, Max Born, and Pascual Jordan formulated the matrix mechanics representation of quantum mechanics.
=== Epiphany at Helgoland ===
In 1925 Werner Heisenberg was working in Göttingen on the problem of calculating the spectral lines of hydrogen. By May 1925 he began trying to describe atomic systems by observables only. On June 7, after weeks of failing to alleviate his hay fever with aspirin and cocaine, Heisenberg left for the pollen-free North Sea island of Helgoland. While there, in between climbing and memorizing poems from Goethe's West-östlicher Diwan, he continued to ponder the spectral issue and eventually realised that adopting non-commuting observables might solve the problem. He later wrote:
It was about three o' clock at night when the final result of the calculation lay before me. At first I was deeply shaken. I was so excited that I could not think of sleep. So I left the house and awaited the sunrise on the top of a rock.: 275
=== The three fundamental papers ===
After Heisenberg returned to Göttingen, he showed Wolfgang Pauli his calculations, commenting at one point:
Everything is still vague and unclear to me, but it seems as if the electrons will no more move on orbits.
On July 9 Heisenberg gave the same paper of his calculations to Max Born, saying that "he had written a crazy paper and did not dare to send it in for publication, and that Born should read it and advise him" prior to publication. Heisenberg then departed for a while, leaving Born to analyse the paper.
In the paper, Heisenberg formulated quantum theory without sharp electron orbits. Hendrik Kramers had earlier calculated the relative intensities of spectral lines in the Sommerfeld model by interpreting the Fourier coefficients of the orbits as intensities. But his answer, like all other calculations in the old quantum theory, was only correct for large orbits.
Heisenberg, after a collaboration with Kramers, began to understand that the transition probabilities were not quite classical quantities, because the only frequencies that appear in the Fourier series should be the ones that are observed in quantum jumps, not the fictional ones that come from Fourier-analyzing sharp classical orbits. He replaced the classical Fourier series with a matrix of coefficients, a fuzzed-out quantum analog of the Fourier series. Classically, the Fourier coefficients give the intensity of the emitted radiation, so in quantum mechanics the magnitude of the matrix elements of the position operator were the intensity of radiation in the bright-line spectrum. The quantities in Heisenberg's formulation were the classical position and momentum, but now they were no longer sharply defined. Each quantity was represented by a collection of Fourier coefficients with two indices, corresponding to the initial and final states.
When Born read the paper, he recognized the formulation as one which could be transcribed and extended to the systematic language of matrices, which he had learned from his study under Jakob Rosanes at Breslau University. Born, with the help of his assistant and former student Pascual Jordan, began immediately to make the transcription and extension, and they submitted their results for publication; the paper was received for publication just 60 days after Heisenberg's paper.
A follow-on paper was submitted for publication before the end of the year by all three authors. (A brief review of Born's role in the development of the matrix mechanics formulation of quantum mechanics along with a discussion of the key formula involving the non-commutativity of the probability amplitudes can be found in an article by Jeremy Bernstein. A detailed historical and technical account can be found in Mehra and Rechenberg's book The Historical Development of Quantum Theory. Volume 3. The Formulation of Matrix Mechanics and Its Modifications 1925–1926.)
Up until this time, matrices were seldom used by physicists; they were considered to belong to the realm of pure mathematics. Gustav Mie had used them in a paper on electrodynamics in 1912 and Born had used them in his work on the lattices theory of crystals in 1921. While matrices were used in these cases, the algebra of matrices with their multiplication did not enter the picture as they did in the matrix formulation of quantum mechanics.
Born, however, had learned matrix algebra from Rosanes, as already noted, but Born had also learned Hilbert's theory of integral equations and quadratic forms for an infinite number of variables as was apparent from a citation by Born of Hilbert's work Grundzüge einer allgemeinen Theorie der Linearen Integralgleichungen published in 1912.
Jordan, too, was well equipped for the task. For a number of years, he had been an assistant to Richard Courant at Göttingen in the preparation of Courant and David Hilbert's book Methoden der mathematischen Physik I, which was published in 1924. This book, fortuitously, contained a great many of the mathematical tools necessary for the continued development of quantum mechanics.
In 1926, John von Neumann became assistant to David Hilbert, and he would coin the term Hilbert space to describe the algebra and analysis which were used in the development of quantum mechanics.
A linchpin contribution to this formulation was achieved in Dirac's reinterpretation/synthesis paper of 1925, which invented the language and framework usually employed today, in full display of the noncommutative structure of the entire construction.
=== Heisenberg's reasoning ===
Before matrix mechanics, the old quantum theory described the motion of a particle by a classical orbit, with well defined position and momentum X(t), P(t), with the restriction that the time integral over one period T of the momentum times the velocity must be a positive integer multiple of the Planck constant
∫
0
T
P
d
X
d
t
d
t
=
∫
0
T
P
d
X
=
n
h
.
{\displaystyle \int _{0}^{T}P\;{\frac {dX}{dt}}\;dt=\int _{0}^{T}P\;dX=nh.}
While this restriction correctly selects orbits with more or less the
right energy values En, the old quantum mechanical formalism did not describe time dependent processes, such as the emission or absorption of radiation.
When a classical particle is weakly coupled to a radiation field, so that the radiative damping can be neglected, it will emit radiation in a pattern that repeats itself every orbital period. The frequencies that make up the outgoing wave are then integer multiples of the orbital frequency, and this is a reflection of the fact that X(t) is periodic, so that its Fourier representation has frequencies 2πn/T only.
X
(
t
)
=
∑
n
=
−
∞
∞
e
2
π
i
n
t
/
T
X
n
.
{\displaystyle X(t)=\sum _{n=-\infty }^{\infty }e^{2\pi int/T}X_{n}.}
The coefficients Xn are complex numbers. The ones with negative frequencies must be the complex conjugates of the ones with positive frequencies, so that X(t) will always be real,
X
n
=
X
−
n
∗
.
{\displaystyle X_{n}=X_{-n}^{*}.}
A quantum mechanical particle, on the other hand, cannot emit radiation continuously; it can only emit photons. Assuming that the quantum particle started in orbit number n, emitted a photon, then ended up in orbit number m, the energy of the photon is En − Em, which means that its frequency is En − Em/h.
For large n and m, but with n − m relatively small, these are the classical frequencies by Bohr's correspondence principle
E
n
−
E
m
≈
h
(
n
−
m
)
T
.
{\displaystyle E_{n}-E_{m}\approx {\frac {h(n-m)}{T}}.}
In the formula above, T is the classical period of either orbit n or orbit m, since the difference between them is higher order in h. But for small n and m, or if n − m is large, the frequencies are not integer multiples of any single frequency.
Since the frequencies that the particle emits are the same as the frequencies in the Fourier description of its motion, this suggests that something in the time-dependent description of the particle is oscillating with frequency En − Em/h. Heisenberg called this quantity Xnm,
and demanded that it should reduce to the classical Fourier coefficients in the classical limit. For large values of n and m but with n − m relatively small,
Xnm is the (n − m)th Fourier coefficient of the classical motion at orbit n. Since Xnm has opposite frequency to Xmn, the condition that X is real becomes
X
n
m
=
X
m
n
∗
.
{\displaystyle X_{nm}=X_{mn}^{*}.}
By definition, Xnm only has the frequency En − Em/h, so its time evolution is simple:
X
n
m
(
t
)
=
e
2
π
i
(
E
n
−
E
m
)
t
/
h
X
n
m
(
0
)
=
e
i
(
E
n
−
E
m
)
t
/
ℏ
X
n
m
(
0
)
.
{\displaystyle X_{nm}(t)=e^{2\pi i(E_{n}-E_{m})t/h}X_{nm}(0)=e^{i(E_{n}-E_{m})t/\hbar }X_{nm}(0).}
This is the original form of Heisenberg's equation of motion.
Given two arrays Xnm and Pnm describing two physical quantities, Heisenberg could form a new array of the same type by combining the terms XnkPkm, which also oscillate with the right frequency. Since the Fourier coefficients of the product of two quantities is the convolution of the Fourier coefficients of each one separately, the correspondence with Fourier series allowed Heisenberg to deduce the rule by which the arrays should be multiplied,
(
X
P
)
m
n
=
∑
k
=
0
∞
X
m
k
P
k
n
.
{\displaystyle (XP)_{mn}=\sum _{k=0}^{\infty }X_{mk}P_{kn}.}
Born pointed out that this is the law of matrix multiplication, so that the position, the momentum, the energy, all the observable quantities in the theory, are interpreted as matrices. Under this multiplication rule, the product depends on the order: XP is different from PX.
The X matrix is a complete description of the motion of a quantum mechanical particle. Because the frequencies in the quantum motion are not multiples of a common frequency, the matrix elements cannot be interpreted as the Fourier coefficients of a sharp classical trajectory. Nevertheless, as matrices, X(t) and P(t) satisfy the classical equations of motion; also see Ehrenfest's theorem, below.
=== Matrix basics ===
When it was introduced by Werner Heisenberg, Max Born and Pascual Jordan in 1925, matrix mechanics was not immediately accepted and was a source of controversy, at first. Schrödinger's later introduction of wave mechanics was greatly favored.
Part of the reason was that Heisenberg's formulation was in an odd mathematical language, for the time, while Schrödinger's formulation was based on familiar wave equations. But there was also a deeper sociological reason. Quantum mechanics had been developing by two paths, one led by Einstein, who emphasized the wave–particle duality he proposed for photons, and the other led by Bohr, that emphasized the discrete energy states and quantum jumps that Bohr discovered. De Broglie had reproduced the discrete energy states within Einstein's framework – the quantum condition is the standing wave condition, and this gave hope to those in the Einstein school that all the discrete aspects of quantum mechanics would be subsumed into a continuous wave mechanics.
Matrix mechanics, on the other hand, came from the Bohr school, which was concerned with discrete energy states and quantum jumps. Bohr's followers did not appreciate physical models that pictured electrons as waves, or as anything at all. They preferred to focus on the quantities that were directly connected to experiments.
In atomic physics, spectroscopy gave observational data on atomic transitions arising from the interactions of atoms with light quanta. The Bohr school required that only those quantities that were in principle measurable by spectroscopy should appear in the theory. These quantities include the energy levels and their intensities but they do not include the exact location of a particle in its Bohr orbit. It is very hard to imagine an experiment that could determine whether an electron in the ground state of a hydrogen atom is to the right or to the left of the nucleus. It was a deep conviction that such questions did not have an answer.
The matrix formulation was built on the premise that all physical observables are represented by matrices, whose elements are indexed by two different energy levels. The set of eigenvalues of the matrix were eventually understood to be the set of all possible values that the observable can have. Since Heisenberg's matrices are Hermitian, the eigenvalues are real.
If an observable is measured and the result is a certain eigenvalue, the corresponding eigenvector is the state of the system immediately after the measurement. The act of measurement in matrix mechanics collapses the state of the system. If one measures two observables simultaneously, the state of the system collapses to a common eigenvector of the two observables. Since most matrices don't have any eigenvectors in common, most observables can never be measured precisely at the same time. This is the uncertainty principle.
If two matrices share their eigenvectors, they can be simultaneously diagonalized. In the basis where they are both diagonal, it is clear that their product does not depend on their order because multiplication of diagonal matrices is just multiplication of numbers. The uncertainty principle, by contrast, is an expression of the fact that often two matrices A and B do not always commute, i.e., that AB − BA does not necessarily equal 0. The fundamental commutation relation of matrix mechanics,
∑
k
(
X
n
k
P
k
m
−
P
n
k
X
k
m
)
=
i
ℏ
δ
n
m
{\displaystyle \sum _{k}\left(X_{nk}P_{km}-P_{nk}X_{km}\right)=i\hbar \,\delta _{nm}}
implies then that there are no states that simultaneously have a definite position and momentum.
This principle of uncertainty holds for many other pairs of observables as well. For example, the energy does not commute with the position either, so it is impossible to precisely determine the position and energy of an electron in an atom.
=== Nobel Prize ===
In 1928, Albert Einstein nominated Heisenberg, Born, and Jordan for the Nobel Prize in Physics. The announcement of the Nobel Prize in Physics for 1932 was delayed until November 1933. It was at that time that it was announced Heisenberg had won the Prize for 1932 "for the creation of quantum mechanics, the application of which has, inter alia, led to the discovery of the allotropic forms of hydrogen" and Erwin Schrödinger and Paul Adrien Maurice Dirac shared the 1933 Prize "for the discovery of new productive forms of atomic theory".
It might well be asked why Born was not awarded the Prize in 1932, along with Heisenberg, and Bernstein proffers speculations on this matter. One of them relates to Jordan joining the Nazi Party on May 1, 1933, and becoming a stormtrooper. Jordan's Party affiliations and Jordan's links to Born may well have affected Born's chance at the Prize at that time. Bernstein further notes that when Born finally won the Prize in 1954, Jordan was still alive, while the Prize was awarded for the statistical interpretation of quantum mechanics, attributable to Born alone.
Heisenberg's reactions to Born for Heisenberg receiving the Prize for 1932 and for Born receiving the Prize in 1954 are also instructive in evaluating whether Born should have shared the Prize with Heisenberg. On November 25, 1933, Born received a letter from Heisenberg in which he said he had been delayed in writing due to a "bad conscience" that he alone had received the Prize "for work done in Göttingen in collaboration – you, Jordan and I". Heisenberg went on to say that Born and Jordan's contribution to quantum mechanics cannot be changed by "a wrong decision from the outside".
In 1954, Heisenberg wrote an article honoring Max Planck for his insight in 1900. In the article, Heisenberg credited Born and Jordan for the final mathematical formulation of matrix mechanics and Heisenberg went on to stress how great their contributions were to quantum mechanics, which were not "adequately acknowledged in the public eye".
== Mathematical development ==
Once Heisenberg introduced the matrices for X and P, he could find their matrix elements in special cases by guesswork, guided by the correspondence principle. Since the matrix elements are the quantum mechanical analogs of Fourier coefficients of the classical orbits, the simplest case is the harmonic oscillator, where the classical position and momentum, X(t) and P(t), are sinusoidal.
=== Harmonic oscillator ===
In units where the mass and frequency of the oscillator are equal to one (see nondimensionalization), the energy of the oscillator is
H
=
1
2
(
P
2
+
X
2
)
.
{\displaystyle H={\tfrac {1}{2}}\left(P^{2}+X^{2}\right).}
The level sets of H are the clockwise orbits, and they are nested circles in phase space. The classical orbit with energy E is
X
(
t
)
=
2
E
cos
(
t
)
,
P
(
t
)
=
−
2
E
sin
(
t
)
.
{\displaystyle X(t)={\sqrt {2E}}\cos(t),\qquad P(t)=-{\sqrt {2E}}\sin(t)~.}
The old quantum condition dictates that the integral of P dX over an orbit, which is the area of the circle in phase space, must be an integer multiple of the Planck constant. The area of the circle of radius √2E is 2πE. So
E
=
n
h
2
π
=
n
ℏ
,
{\displaystyle E={\frac {nh}{2\pi }}=n\hbar \,,}
or, in natural units where ħ = 1, the energy is an integer.
The Fourier components of X(t) and P(t) are simple, and more so if they are combined into the quantities
A
(
t
)
=
X
(
t
)
+
i
P
(
t
)
=
2
E
e
−
i
t
,
A
†
(
t
)
=
X
(
t
)
−
i
P
(
t
)
=
2
E
e
i
t
.
{\displaystyle A(t)=X(t)+iP(t)={\sqrt {2E}}\,e^{-it},\quad A^{\dagger }(t)=X(t)-iP(t)={\sqrt {2E}}\,e^{it}.}
Both A and A† have only a single frequency, and X and P can be recovered from their sum and difference.
Since A(t) has a classical Fourier series with only the lowest frequency, and the matrix element Amn is the (m − n)th Fourier coefficient of the classical orbit, the matrix for A is nonzero only on the line just above the diagonal, where it is equal to √2En. The matrix for A† is likewise only nonzero on the line below the diagonal, with the same elements. Thus, from A and A†, reconstruction yields
2
X
(
0
)
=
ℏ
[
0
1
0
0
0
⋯
1
0
2
0
0
⋯
0
2
0
3
0
⋯
0
0
3
0
4
⋯
⋮
⋮
⋮
⋮
⋮
⋱
]
,
{\displaystyle {\sqrt {2}}X(0)={\sqrt {\hbar }}\;{\begin{bmatrix}0&{\sqrt {1}}&0&0&0&\cdots \\{\sqrt {1}}&0&{\sqrt {2}}&0&0&\cdots \\0&{\sqrt {2}}&0&{\sqrt {3}}&0&\cdots \\0&0&{\sqrt {3}}&0&{\sqrt {4}}&\cdots \\\vdots &\vdots &\vdots &\vdots &\vdots &\ddots \\\end{bmatrix}},}
and
2
P
(
0
)
=
ℏ
[
0
−
i
1
0
0
0
⋯
i
1
0
−
i
2
0
0
⋯
0
i
2
0
−
i
3
0
⋯
0
0
i
3
0
−
i
4
⋯
⋮
⋮
⋮
⋮
⋮
⋱
]
,
{\displaystyle {\sqrt {2}}P(0)={\sqrt {\hbar }}\;{\begin{bmatrix}0&-i{\sqrt {1}}&0&0&0&\cdots \\i{\sqrt {1}}&0&-i{\sqrt {2}}&0&0&\cdots \\0&i{\sqrt {2}}&0&-i{\sqrt {3}}&0&\cdots \\0&0&i{\sqrt {3}}&0&-i{\sqrt {4}}&\cdots \\\vdots &\vdots &\vdots &\vdots &\vdots &\ddots \\\end{bmatrix}},}
which, up to the choice of units, are the Heisenberg matrices for the harmonic oscillator. Both matrices are Hermitian, since they are constructed from the Fourier coefficients of real quantities.
Finding X(t) and P(t) is direct, since they are quantum Fourier coefficients so they evolve simply with time,
X
m
n
(
t
)
=
X
m
n
(
0
)
e
i
(
E
m
−
E
n
)
t
,
P
m
n
(
t
)
=
P
m
n
(
0
)
e
i
(
E
m
−
E
n
)
t
.
{\displaystyle X_{mn}(t)=X_{mn}(0)e^{i(E_{m}-E_{n})t},\quad P_{mn}(t)=P_{mn}(0)e^{i(E_{m}-E_{n})t}~.}
The matrix product of X and P is not hermitian, but has a real and imaginary part. The real part is one half the symmetric expression XP + PX, while the imaginary part is proportional to the commutator
[
X
,
P
]
=
(
X
P
−
P
X
)
.
{\displaystyle [X,P]=(XP-PX).}
It is simple to verify explicitly that XP − PX in the case of the harmonic oscillator, is iħ, multiplied by the identity.
It is likewise simple to verify that the matrix
H
=
1
2
(
X
2
+
P
2
)
{\displaystyle H={\tfrac {1}{2}}\left(X^{2}+P^{2}\right)}
is a diagonal matrix, with eigenvalues Ei.
=== Conservation of energy ===
The harmonic oscillator is an important case. Finding the matrices is easier than determining the general conditions from these special forms. For this reason, Heisenberg investigated the anharmonic oscillator, with Hamiltonian
H
=
1
2
P
2
+
1
2
X
2
+
ε
X
3
.
{\displaystyle H={\tfrac {1}{2}}P^{2}+{\tfrac {1}{2}}X^{2}+\varepsilon X^{3}~.}
In this case, the X and P matrices are no longer simple off-diagonal matrices, since the corresponding classical orbits are slightly squashed and displaced, so that they have Fourier coefficients at every classical frequency. To determine the matrix elements, Heisenberg required that the classical equations of motion be obeyed as matrix equations,
d
X
d
t
=
P
,
d
P
d
t
=
−
X
−
3
ε
X
2
.
{\displaystyle {\frac {dX}{dt}}=P~,\qquad {\frac {dP}{dt}}=-X-3\varepsilon X^{2}~.}
He noticed that if this could be done, then H, considered as a matrix function of X and P, will have zero time derivative.
d
H
d
t
=
P
∗
d
P
d
t
+
(
X
+
3
ε
X
2
)
∗
d
X
d
t
=
0
,
{\displaystyle {\frac {dH}{dt}}=P*{\frac {dP}{dt}}+\left(X+3\varepsilon X^{2}\right)*{\frac {dX}{dt}}=0~,}
where A∗B is the anticommutator,
A
∗
B
=
1
2
(
A
B
+
B
A
)
.
{\displaystyle A*B={\tfrac {1}{2}}(AB+BA)~.}
Given that all the off diagonal elements have a nonzero frequency; H being constant implies that H is diagonal.
It was clear to Heisenberg that in this system, the energy could be exactly conserved in an arbitrary quantum system, a very encouraging sign.
The process of emission and absorption of photons seemed to demand that the conservation of energy will hold at best on average. If a wave containing exactly one photon passes over some atoms, and one of them absorbs it, that atom needs to tell the others that they can't absorb the photon anymore. But if the atoms are far apart, any signal cannot reach the other atoms in time, and they might end up absorbing the same photon anyway and dissipating the energy to the environment. When the signal reached them, the other atoms would have to somehow recall that energy. This paradox led Bohr, Kramers and Slater to abandon exact conservation of energy. Heisenberg's formalism, when extended to include the electromagnetic field, was obviously going to sidestep this problem, a hint that the interpretation of the theory will involve wavefunction collapse.
=== Differentiation trick — canonical commutation relations ===
Demanding that the classical equations of motion are preserved is not a strong enough condition to determine the matrix elements. The Planck constant does not appear in the classical equations, so that the matrices could be constructed for many different values of ħ and still satisfy the equations of motion, but with different energy levels.
So, in order to implement his program, Heisenberg needed to use the old quantum condition to fix the energy levels, then fill in the matrices with Fourier coefficients of the classical equations, then alter the matrix coefficients and the energy levels slightly to make sure the classical equations are satisfied. This is clearly not satisfactory. The old quantum conditions refer to the area enclosed by the sharp classical orbits, which do not exist in the new formalism.
The most important thing that Heisenberg discovered is how to translate the old quantum condition into a simple statement in matrix mechanics.
To do this, he investigated the action integral as a matrix quantity,
∫
0
T
∑
k
P
m
k
(
t
)
d
X
k
n
d
t
d
t
≈
?
J
m
n
.
{\displaystyle \int _{0}^{T}\sum _{k}P_{mk}(t){\frac {dX_{kn}}{dt}}dt\,\,{\stackrel {\scriptstyle ?}{\approx }}\,\,J_{mn}~.}
There are several problems with this integral, all stemming from the incompatibility of the matrix formalism with the old picture of orbits. Which period T should be used? Semiclassically, it should be either m or n, but the difference is order ħ, and an answer to order ħ is sought. The quantum condition tells us that Jmn is 2πn on the diagonal, so the fact that J is classically constant tells us that the off-diagonal elements are zero.
His crucial insight was to differentiate the quantum condition with respect to n. This idea only makes complete sense in the classical limit, where n is not an integer but the continuous action variable J, but Heisenberg performed analogous manipulations with matrices, where the intermediate expressions are sometimes discrete differences and sometimes derivatives.
In the following discussion, for the sake of clarity, the differentiation will be performed on the classical variables, and the transition to matrix mechanics will be done afterwards, guided by the correspondence principle.
In the classical setting, the derivative is the derivative with respect to J of the integral which defines J, so it is tautologically equal to 1.
d
d
J
∫
0
T
P
d
X
=
1
=
∫
0
T
d
t
(
d
P
d
J
d
X
d
t
+
P
d
d
J
d
X
d
t
)
=
∫
0
T
d
t
(
d
P
d
J
d
X
d
t
−
d
P
d
t
d
X
d
J
)
{\displaystyle {\begin{aligned}{}{\frac {d}{dJ}}\int _{0}^{T}PdX&=1\\&=\int _{0}^{T}dt\left({\frac {dP}{dJ}}{\frac {dX}{dt}}+P{\frac {d}{dJ}}{\frac {dX}{dt}}\right)\\&=\int _{0}^{T}dt\left({\frac {dP}{dJ}}{\frac {dX}{dt}}-{\frac {dP}{dt}}{\frac {dX}{dJ}}\right)\end{aligned}}}
where the derivatives dP/dJ and dX/dJ should be interpreted as differences with respect to J at corresponding times on nearby orbits, exactly what would be obtained if the Fourier coefficients of the orbital motion were differentiated. (These derivatives are symplectically orthogonal in phase space to the time derivatives dP/dt and dX/dt).
The final expression is clarified by introducing the variable canonically conjugate to J, which is called the angle variable θ: The derivative with respect to time is a derivative with respect to θ, up to a factor of 2πT,
2
π
T
∫
0
T
d
t
(
d
P
d
J
d
X
d
θ
−
d
P
d
θ
d
X
d
J
)
=
1
.
{\displaystyle {\frac {2\pi }{T}}\int _{0}^{T}dt\left({\frac {dP}{dJ}}{\frac {dX}{d\theta }}-{\frac {dP}{d\theta }}{\frac {dX}{dJ}}\right)=1\,.}
So the quantum condition integral is the average value over one cycle of the Poisson bracket of X and P.
An analogous differentiation of the Fourier series of P dX demonstrates that the off-diagonal elements of the Poisson bracket are all zero. The Poisson bracket of two canonically conjugate variables, such as X and P, is the constant value 1, so this integral really is the average value of 1; so it is 1, as we knew all along, because it is dJ/dJ after all. But Heisenberg, Born and Jordan, unlike Dirac, were not familiar with the theory of Poisson brackets, so, for them, the differentiation effectively evaluated {X, P} in J,θ coordinates.
The Poisson Bracket, unlike the action integral, does have a simple translation to matrix mechanics – it normally corresponds to the imaginary part of the product of two variables, the commutator.
To see this, examine the (antisymmetrized) product of two matrices A and B in the correspondence limit, where the matrix elements are slowly varying functions of the index, keeping in mind that the answer is zero classically.
In the correspondence limit, when indices m, n are large and nearby, while k, r are small, the rate of change of the matrix elements in the diagonal direction is the matrix element of the J derivative of the corresponding classical quantity. So it is possible to shift any matrix element diagonally through the correspondence,
A
(
m
+
r
)
(
n
+
r
)
−
A
m
n
≈
r
(
d
A
d
J
)
m
n
{\displaystyle A_{(m+r)(n+r)}-A_{mn}\approx r\;\left({\frac {dA}{dJ}}\right)_{mn}}
where the right hand side is really only the (m − n)th Fourier component of dA/dJ at the orbit near m to this semiclassical order, not a full well-defined matrix.
The semiclassical time derivative of a matrix element is obtained up to a factor of i by multiplying by the distance from the diagonal,
i
k
A
m
(
m
+
k
)
≈
(
T
2
π
d
A
d
t
)
m
(
m
+
k
)
=
(
d
A
d
θ
)
m
(
m
+
k
)
.
{\displaystyle ikA_{m(m+k)}\approx \left({\frac {T}{2\pi }}{\frac {dA}{dt}}\right)_{m(m+k)}=\left({\frac {dA}{d\theta }}\right)_{m(m+k)}\,.}
since the coefficient Am(m+k) is semiclassically the kth Fourier coefficient of the mth classical orbit.
The imaginary part of the product of A and B can be evaluated by shifting the matrix elements around so as to reproduce the classical answer, which is zero.
The leading nonzero residual is then given entirely by the shifting. Since all the matrix elements are at indices which have a small distance from the large index position (m,m), it helps to introduce two temporary notations:
A[r,k] = A(m+r)(m+k) for the matrices, and dA/dJ[r] for the rth Fourier components of classical quantities,
(
A
B
−
B
A
)
[
0
,
k
]
=
∑
r
=
−
∞
∞
(
A
[
0
,
r
]
B
[
r
,
k
]
−
A
[
r
,
k
]
B
[
0
,
r
]
)
=
∑
r
(
A
[
−
r
+
k
,
k
]
+
(
r
−
k
)
d
A
d
J
[
r
]
)
(
B
[
0
,
k
−
r
]
+
r
d
B
d
J
[
r
−
k
]
)
−
∑
r
A
[
r
,
k
]
B
[
0
,
r
]
.
{\displaystyle {\begin{aligned}(AB-BA)[0,k]&=\sum _{r=-\infty }^{\infty }{\bigl (}A[0,r]B[r,k]-A[r,k]B[0,r]{\bigr )}\\&=\sum _{r}\left(A[-r+k,k]+(r-k){\frac {dA}{dJ}}[r]\right)\left(B[0,k-r]+r{\frac {dB}{dJ}}[r-k]\right)-\sum _{r}A[r,k]B[0,r]\,.\end{aligned}}}
Flipping the summation variable in the first sum from r to r′ = k − r, the matrix element becomes,
∑
r
′
(
A
[
r
′
,
k
]
−
r
′
d
A
d
J
[
k
−
r
′
]
)
(
B
[
0
,
r
′
]
+
(
k
−
r
′
)
d
B
d
J
[
r
′
]
)
−
∑
r
A
[
r
,
k
]
B
[
0
,
r
]
{\displaystyle \sum _{r'}\left(A[r',k]-r'{\frac {dA}{dJ}}[k-r']\right)\left(B[0,r']+(k-r'){\frac {dB}{dJ}}[r']\right)-\sum _{r}A[r,k]B[0,r]}
and it is clear that the principal (classical) part cancels.
The leading quantum part, neglecting the higher order product of derivatives in the residual expression, is then equal to
∑
r
′
(
d
B
d
J
[
r
′
]
(
k
−
r
′
)
A
[
r
′
,
k
]
−
d
A
d
J
[
k
−
r
′
]
r
′
B
[
0
,
r
′
]
)
{\displaystyle \sum _{r'}\left({\frac {dB}{dJ}}[r'](k-r')A[r',k]-{\frac {dA}{dJ}}[k-r']r'B[0,r']\right)}
so that, finally,
(
A
B
−
B
A
)
[
0
,
k
]
=
∑
r
′
(
d
B
d
J
[
r
′
]
i
d
A
d
θ
[
k
−
r
′
]
−
d
A
d
J
[
k
−
r
′
]
i
d
B
d
θ
[
r
′
]
)
{\displaystyle (AB-BA)[0,k]=\sum _{r'}\left({\frac {dB}{dJ}}[r']i{\frac {dA}{d\theta }}[k-r']-{\frac {dA}{dJ}}[k-r']i{\frac {dB}{d\theta }}[r']\right)}
which can be identified with i times the kth classical Fourier component of the Poisson bracket.
Heisenberg's original differentiation trick was eventually extended to a full semiclassical derivation of the quantum condition, in collaboration with Born and Jordan.
Once they were able to establish that
i
ℏ
{
X
,
P
}
P
B
⟼
[
X
,
P
]
≡
X
P
−
P
X
=
i
ℏ
,
{\displaystyle i\hbar \{X,P\}_{\mathrm {PB} }\qquad \longmapsto \qquad [X,P]\equiv XP-PX=i\hbar \,,}
this condition replaced and extended the old quantization rule, allowing the matrix elements of P and X for an arbitrary system to be determined simply from the form of the Hamiltonian.
The new quantization rule was assumed to be universally true, even though the derivation from the old quantum theory required semiclassical reasoning.
(A full quantum treatment, however, for more elaborate arguments of the brackets, was appreciated in the 1940s to amount to extending Poisson brackets to Moyal brackets.)
=== State vectors and the Heisenberg equation ===
To make the transition to standard quantum mechanics, the most important further addition was the quantum state vector, now written |ψ⟩,
which is the vector that the matrices act on. Without the state vector, it is not clear which particular motion the Heisenberg matrices are describing, since they include all the motions somewhere.
The interpretation of the state vector, whose components are written ψm, was furnished by Born. This interpretation is statistical: the result of a measurement of the physical quantity corresponding to the matrix A is random, with an average value equal to
∑
m
n
ψ
m
∗
A
m
n
ψ
n
.
{\displaystyle \sum _{mn}\psi _{m}^{*}A_{mn}\psi _{n}\,.}
Alternatively, and equivalently, the state vector gives the probability amplitude ψn for the quantum system to be in the energy state n.
Once the state vector was introduced, matrix mechanics could be rotated to any basis, where the H matrix need no longer be diagonal. The Heisenberg equation of motion in its original form states that Amn evolves in time like a Fourier component,
A
m
n
(
t
)
=
e
i
(
E
m
−
E
n
)
t
A
m
n
(
0
)
,
{\displaystyle A_{mn}(t)=e^{i(E_{m}-E_{n})t}A_{mn}(0)~,}
which can be recast in differential form
d
A
m
n
d
t
=
i
(
E
m
−
E
n
)
A
m
n
,
{\displaystyle {\frac {dA_{mn}}{dt}}=i(E_{m}-E_{n})A_{mn}~,}
and it can be restated so that it is true in an arbitrary basis, by noting that the H matrix is diagonal with diagonal values Em,
d
A
d
t
=
i
(
H
A
−
A
H
)
.
{\displaystyle {\frac {dA}{dt}}=i(HA-AH)~.}
This is now a matrix equation, so it holds in any basis. This is the modern form of the Heisenberg equation of motion.
Its formal solution is:
A
(
t
)
=
e
i
H
t
A
(
0
)
e
−
i
H
t
.
{\displaystyle A(t)=e^{iHt}A(0)e^{-iHt}~.}
All these forms of the equation of motion above say the same thing, that A(t) is equivalent to A(0), through a basis rotation by the unitary matrix eiHt, a systematic picture elucidated by Dirac in his bra–ket notation.
Conversely, by rotating the basis for the state vector at each time by eiHt, the time dependence in the matrices can be undone. The matrices are now time independent, but the state vector rotates,
|
ψ
(
t
)
⟩
=
e
−
i
H
t
|
ψ
(
0
)
⟩
,
d
|
ψ
⟩
d
t
=
−
i
H
|
ψ
⟩
.
{\displaystyle |\psi (t)\rangle =e^{-iHt}|\psi (0)\rangle ,\qquad {\frac {d|\psi \rangle }{dt}}=-iH|\psi \rangle \,.}
This is the Schrödinger equation for the state vector, and this time-dependent change of basis amounts to transformation to the Schrödinger picture, with ⟨x|ψ⟩ = ψ(x).
In quantum mechanics in the Heisenberg picture the state vector, |ψ⟩ does not change with time, while an observable A satisfies the Heisenberg equation of motion,
The extra term is for operators such as
A
=
(
X
+
t
2
P
)
{\displaystyle A=\left(X+t^{2}P\right)}
which have an explicit time dependence, in addition to the time dependence from the unitary evolution discussed.
The Heisenberg picture does not distinguish time from space, so it is better suited to relativistic theories than the Schrödinger equation. Moreover, the similarity to classical physics is more manifest: the Hamiltonian equations of motion for classical mechanics are recovered by replacing the commutator above by the Poisson bracket (see also below). By the Stone–von Neumann theorem, the Heisenberg picture and the Schrödinger picture must be unitarily equivalent, as detailed below.
== Further results ==
Matrix mechanics rapidly developed into modern quantum mechanics, and gave interesting physical results on the spectra of atoms.
=== Wave mechanics ===
Jordan noted that the commutation relations ensure that P acts as a differential operator.
The operator identity
[
a
,
b
c
]
=
a
b
c
−
b
c
a
=
a
b
c
−
b
a
c
+
b
a
c
−
b
c
a
=
[
a
,
b
]
c
+
b
[
a
,
c
]
{\displaystyle [a,bc]=abc-bca=abc-bac+bac-bca=[a,b]c+b[a,c]}
allows the evaluation of the commutator of P with any power of X, and it implies that
[
P
,
X
n
]
=
−
i
n
X
n
−
1
{\displaystyle \left[P,X^{n}\right]=-in~X^{n-1}}
which, together with linearity, implies that a P-commutator effectively differentiates any analytic matrix function of X.
Assuming limits are defined sensibly, this extends to arbitrary functions−but the extension need not be made explicit until a certain degree of mathematical rigor is required,
Since X is a Hermitian matrix, it should be diagonalizable, and it will be clear from the eventual form of P that every real number can be an eigenvalue. This makes some of the mathematics subtle, since there is a separate eigenvector for every point in space.
In the basis where X is diagonal, an arbitrary state can be written as a superposition of states with eigenvalues x,
|
ψ
⟩
=
∫
x
ψ
(
x
)
|
x
⟩
,
{\displaystyle |\psi \rangle =\int _{x}\psi (x)|x\rangle \,,}
so that ψ(x) = ⟨x|ψ⟩, and the operator X multiplies each eigenvector by x,
X
|
ψ
⟩
=
∫
x
x
ψ
(
x
)
|
x
⟩
.
{\displaystyle X|\psi \rangle =\int _{x}x\psi (x)|x\rangle ~.}
Define a linear operator D which differentiates ψ,
D
∫
x
ψ
(
x
)
|
x
⟩
=
∫
x
ψ
′
(
x
)
|
x
⟩
,
{\displaystyle D\int _{x}\psi (x)|x\rangle =\int _{x}\psi '(x)|x\rangle \,,}
and note that
(
D
X
−
X
D
)
|
ψ
⟩
=
∫
x
[
(
x
ψ
(
x
)
)
′
−
x
ψ
′
(
x
)
]
|
x
⟩
=
∫
x
ψ
(
x
)
|
x
⟩
=
|
ψ
⟩
,
{\displaystyle (DX-XD)|\psi \rangle =\int _{x}\left[\left(x\psi (x)\right)'-x\psi '(x)\right]|x\rangle =\int _{x}\psi (x)|x\rangle =|\psi \rangle \,,}
so that the operator −iD obeys the same commutation relation as P. Thus, the difference between P and −iD must commute with X,
[
P
+
i
D
,
X
]
=
0
,
{\displaystyle [P+iD,X]=0\,,}
so it may be simultaneously diagonalized with X: its value acting on any eigenstate of X is some function f of the eigenvalue x.
This function must be real, because both P and −iD are Hermitian,
(
P
+
i
D
)
|
x
⟩
=
f
(
x
)
|
x
⟩
,
{\displaystyle (P+iD)|x\rangle =f(x)|x\rangle \,,}
rotating each state |x⟩ by a phase f(x), that is, redefining the phase of the wavefunction:
ψ
(
x
)
→
e
−
i
f
(
x
)
ψ
(
x
)
.
{\displaystyle \psi (x)\rightarrow e^{-if(x)}\psi (x)\,.}
The operator iD is redefined by an amount:
i
D
→
i
D
+
f
(
X
)
,
{\displaystyle iD\rightarrow iD+f(X)\,,}
which means that, in the rotated basis, P is equal to −iD.
Hence, there is always a basis for the eigenvalues of X where the action of P on any wavefunction is known:
P
∫
x
ψ
(
x
)
|
x
⟩
=
∫
x
−
i
ψ
′
(
x
)
|
x
⟩
,
{\displaystyle P\int _{x}\psi (x)|x\rangle =\int _{x}-i\psi '(x)|x\rangle \,,}
and the Hamiltonian in this basis is a linear differential operator on the state-vector components,
[
P
2
2
m
+
V
(
X
)
]
∫
x
ψ
x
|
x
⟩
=
∫
x
[
−
1
2
m
∂
2
∂
x
2
+
V
(
x
)
]
ψ
x
|
x
⟩
{\displaystyle \left[{\frac {P^{2}}{2m}}+V(X)\right]\int _{x}\psi _{x}|x\rangle =\int _{x}\left[-{\frac {1}{2m}}{\frac {\partial ^{2}}{\partial x^{2}}}+V(x)\right]\psi _{x}|x\rangle }
Thus, the equation of motion for the state vector is but a celebrated differential equation,
Since D is a differential operator, in order for it to be sensibly defined, there must be eigenvalues of X which neighbors every given value. This suggests that the only possibility is that the space of all eigenvalues of X is all real numbers, and that P is iD, up to a phase rotation.
To make this rigorous requires a sensible discussion of the limiting space of functions, and in this space this is the Stone–von Neumann theorem: any operators X and P which obey the commutation relations can be made to act on a space of wavefunctions, with P a derivative operator. This implies that a Schrödinger picture is always available.
Matrix mechanics easily extends to many degrees of freedom in a natural way. Each degree of freedom has a separate X operator and a separate effective differential operator P, and the wavefunction is a function of all the possible eigenvalues of the independent commuting X variables.
[
X
i
,
X
j
]
=
0
[
P
i
,
P
j
]
=
0
[
X
i
,
P
j
]
=
i
δ
i
j
.
{\displaystyle {\begin{aligned}\left[X_{i},X_{j}\right]&=0\\[1ex]\left[P_{i},P_{j}\right]&=0\\[1ex]\left[X_{i},P_{j}\right]&=i\delta _{ij}\,.\end{aligned}}}
In particular, this means that a system of N interacting particles in 3 dimensions is described by one vector whose components in a basis where all the X are diagonal is a mathematical function of 3N-dimensional space describing all their possible positions, effectively a much bigger collection of values than the mere collection of N three-dimensional wavefunctions in one physical space. Schrödinger came to the same conclusion independently, and eventually proved the equivalence of his own formalism to Heisenberg's.
Since the wavefunction is a property of the whole system, not of any one part, the description in quantum mechanics is not entirely local. The description of several quantum particles has them correlated, or entangled. This entanglement leads to strange correlations between distant particles which violate the classical Bell's inequality.
Even if the particles can only be in just two positions, the wavefunction for N particles requires 2N complex numbers, one for each total configuration of positions. This is exponentially many numbers in N, so simulating quantum mechanics on a computer requires exponential resources. Conversely, this suggests that it might be possible to find quantum systems of size N which physically compute the answers to problems which classically require 2N bits to solve. This is the aspiration behind quantum computing.
=== Ehrenfest theorem ===
For the time-independent operators X and P, ∂A/∂t = 0 so the Heisenberg equation above reduces to:
i
ℏ
d
A
d
t
=
[
A
,
H
]
=
A
H
−
H
A
,
{\displaystyle i\hbar {\frac {dA}{dt}}=[A,H]=AH-HA,}
where the square brackets [ , ] denote the commutator. For a Hamiltonian which is p2/2m + V(x), the X and P operators satisfy:
d
X
d
t
=
P
m
,
d
P
d
t
=
−
∇
V
,
{\displaystyle {\frac {dX}{dt}}={\frac {P}{m}},\quad {\frac {dP}{dt}}=-\nabla V,}
where the first is classically the velocity, and second is classically the force, or potential gradient. These reproduce Hamilton's form of Newton's laws of motion. In the Heisenberg picture, the X and P operators satisfy the classical equations of motion. You can take the expectation value of both sides of the equation to see that, in any state |ψ⟩:
d
d
t
⟨
X
⟩
=
d
d
t
⟨
ψ
|
X
|
ψ
⟩
=
1
m
⟨
ψ
|
P
|
ψ
⟩
=
1
m
⟨
P
⟩
d
d
t
⟨
P
⟩
=
d
d
t
⟨
ψ
|
P
|
ψ
⟩
=
⟨
ψ
|
(
−
∇
V
)
|
ψ
⟩
=
−
⟨
∇
V
⟩
.
{\displaystyle {\begin{aligned}{\frac {d}{dt}}\langle X\rangle &={\frac {d}{dt}}\langle \psi |X|\psi \rangle ={\frac {1}{m}}\langle \psi |P|\psi \rangle ={\frac {1}{m}}\langle P\rangle \\[1.5ex]{\frac {d}{dt}}\langle P\rangle &={\frac {d}{dt}}\langle \psi |P|\psi \rangle =\langle \psi |(-\nabla V)|\psi \rangle =-\langle \nabla V\rangle \,.\end{aligned}}}
So Newton's laws are exactly obeyed by the expected values of the operators in any given state. This is Ehrenfest's theorem, which is an obvious corollary of the Heisenberg equations of motion, but is less trivial in the Schrödinger picture, where Ehrenfest discovered it.
=== Transformation theory ===
In classical mechanics, a canonical transformation of phase space coordinates is one which preserves the structure of the Poisson brackets. The new variables x′, p′ have the same Poisson brackets with each other as the original variables x, p. Time evolution is a canonical transformation, since the phase space at any time is just as good a choice of variables as the phase space at any other time.
The Hamiltonian flow is the canonical transformation:
x
→
x
+
d
x
=
x
+
∂
H
∂
p
d
t
p
→
p
+
d
p
=
p
−
∂
H
∂
x
d
t
.
{\displaystyle {\begin{aligned}x&\rightarrow x+dx=x+{\frac {\partial H}{\partial p}}dt\\[1ex]p&\rightarrow p+dp=p-{\frac {\partial H}{\partial x}}dt~.\end{aligned}}}
Since the Hamiltonian can be an arbitrary function of x and p, there are such infinitesimal canonical transformations corresponding to every classical quantity G, where G serves as the Hamiltonian to generate a flow of points in phase space for an increment of time s,
d
x
=
∂
G
∂
p
d
s
=
{
G
,
X
}
d
s
d
p
=
−
∂
G
∂
x
d
s
=
{
G
,
P
}
d
s
.
{\displaystyle {\begin{aligned}dx&={\frac {\partial G}{\partial p}}ds=\left\{G,X\right\}ds\\[1ex]dp&=-{\frac {\partial G}{\partial x}}ds=\left\{G,P\right\}ds\,.\end{aligned}}}
For a general function A(x,p) on phase space, its infinitesimal change at every step ds under this map is
d
A
=
∂
A
∂
x
d
x
+
∂
A
∂
p
d
p
=
{
A
,
G
}
d
s
.
{\displaystyle dA={\frac {\partial A}{\partial x}}dx+{\frac {\partial A}{\partial p}}dp=\{A,G\}ds\,.}
The quantity G is called the infinitesimal generator of the canonical transformation.
In quantum mechanics, the quantum analog G is now a Hermitian matrix, and the equations of motion are given by commutators,
d
A
=
i
[
G
,
A
]
d
s
.
{\displaystyle dA=i[G,A]ds\,.}
The infinitesimal canonical motions can be formally integrated, just as the Heisenberg equation of motion were integrated,
A
′
=
U
†
A
U
{\displaystyle A'=U^{\dagger }AU}
where U = eiGs and s is an arbitrary parameter.
The definition of a quantum canonical transformation is thus an arbitrary unitary change of basis on the space of all state vectors. U is an arbitrary unitary matrix, a complex rotation in phase space,
U
†
=
U
−
1
.
{\displaystyle U^{\dagger }=U^{-1}\,.}
These transformations leave the sum of the absolute square of the wavefunction components invariant, while they take states which are multiples of each other (including states which are imaginary multiples of each other) to states which are the same multiple of each other.
The interpretation of the matrices is that they act as generators of motions on the space of states.
For example, the motion generated by P can be found by solving the Heisenberg equation of motion using P as a Hamiltonian,
d
X
=
i
[
X
,
P
]
d
s
=
d
s
d
P
=
i
[
P
,
P
]
d
s
=
0
.
{\displaystyle {\begin{aligned}dX&=i[X,P]ds=ds\\[1ex]dP&=i[P,P]ds=0\,.\end{aligned}}}
These are translations of the matrix X by a multiple of the identity matrix,
X
→
X
+
s
I
.
{\displaystyle X\rightarrow X+sI~.}
This is the interpretation of the derivative operator D: eiPs = eD, the exponential of a derivative operator is a translation (so Lagrange's shift operator).
The X operator likewise generates translations in P. The Hamiltonian generates translations in time, the angular momentum generates rotations in physical space, and the operator X2 + P2 generates rotations in phase space.
When a transformation, like a rotation in physical space, commutes with the Hamiltonian, the transformation is called a symmetry (behind a degeneracy) of the Hamiltonian – the Hamiltonian expressed in terms of rotated coordinates is the same as the original Hamiltonian. This means that the change in the Hamiltonian under the infinitesimal symmetry generator L vanishes,
d
H
d
s
=
i
[
L
,
H
]
=
0
.
{\displaystyle {\frac {dH}{ds}}=i[L,H]=0\,.}
It then follows that the change in the generator under time translation also vanishes,
d
L
d
t
=
i
[
H
,
L
]
=
0
{\displaystyle {\frac {dL}{dt}}=i[H,L]=0}
so that the matrix L is constant in time: it is conserved.
The one-to-one association of infinitesimal symmetry generators and conservation laws was discovered by Emmy Noether for classical mechanics, where the commutators are Poisson brackets, but the quantum-mechanical reasoning is identical. In quantum mechanics, any unitary symmetry transformation yields a conservation law, since if the matrix U has the property that
U
−
1
H
U
=
H
{\displaystyle U^{-1}HU=H}
so it follows that
U
H
=
H
U
{\displaystyle UH=HU}
and that the time derivative of U is zero – it is conserved.
The eigenvalues of unitary matrices are pure phases, so that the value of a unitary conserved quantity is a complex number of unit magnitude, not a real number. Another way of saying this is that a unitary matrix is the exponential of i times a Hermitian matrix, so that the additive conserved real quantity, the phase, is only well-defined up to an integer multiple of 2π. Only when the unitary symmetry matrix is part of a family that comes arbitrarily close to the identity are the conserved real quantities single-valued, and then the demand that they are conserved become a much more exacting constraint.
Symmetries which can be continuously connected to the identity are called continuous, and translations, rotations, and boosts are examples. Symmetries which cannot be continuously connected to the identity are discrete, and the operation of space-inversion, or parity, and charge conjugation are examples.
The interpretation of the matrices as generators of canonical transformations is due to Paul Dirac. The correspondence between symmetries and matrices was shown by Eugene Wigner to be complete, if antiunitary matrices which describe symmetries which include time-reversal are included.
=== Selection rules ===
It was physically clear to Heisenberg that the absolute squares of the matrix elements of X, which are the Fourier coefficients of the oscillation, would yield the rate of emission of electromagnetic radiation.
In the classical limit of large orbits, if a charge with position X(t) and charge q is oscillating next to an equal and opposite charge at position 0, the instantaneous dipole moment is q X(t), and the time variation of this moment translates directly into the space-time variation of the vector potential, which yields nested outgoing spherical waves.
For atoms, the wavelength of the emitted light is about 10,000 times the atomic radius, and the dipole moment is the only contribution to the radiative field, while all other details of the atomic charge distribution can be ignored.
Ignoring back-reaction, the power radiated in each outgoing mode is a sum of separate contributions from the square of each independent time Fourier mode of d,
P
(
ω
)
=
2
3
ω
4
|
d
i
|
2
.
{\displaystyle P(\omega )={\tfrac {2}{3}}{\omega ^{4}}|d_{i}|^{2}~.}
Now, in Heisenberg's representation, the Fourier coefficients of the dipole moment are the matrix elements of X. This correspondence allowed Heisenberg to provide the rule for the transition intensities, the fraction of the time that, starting from an initial state i, a photon is emitted and the atom jumps to a final state j,
P
i
j
=
2
3
(
E
i
−
E
j
)
4
|
X
i
j
|
2
.
{\displaystyle P_{ij}={\tfrac {2}{3}}\left(E_{i}-E_{j}\right)^{4}\left|X_{ij}\right|^{2}\,.}
This then allowed the magnitude of the matrix elements to be interpreted statistically: they give the intensity of the spectral lines, the probability for quantum jumps from the emission of dipole radiation.
Since the transition rates are given by the matrix elements of X, wherever Xij is zero, the corresponding transition should be absent. These were called the selection rules, which were a puzzle until the advent of matrix mechanics.
An arbitrary state of the hydrogen atom, ignoring spin, is labelled by |n;l,m⟩, where the value of l is a measure of the total orbital angular momentum and m is its z-component, which defines the orbit orientation. The components of the angular momentum pseudovector are
L
i
=
ε
i
j
k
X
j
P
k
{\displaystyle L_{i}=\varepsilon _{ijk}X^{j}P^{k}}
where the products in this expression are independent of order and real, because different components of X and P commute.
The commutation relations of L with all three coordinate matrices X, Y, Z (or with any vector) are easy to find,
[
L
i
,
X
j
]
=
i
ε
i
j
k
X
k
,
{\displaystyle \left[L_{i},X_{j}\right]=i\varepsilon _{ijk}X_{k}\,,}
which confirms that the operator L generates rotations between the three components of the vector of coordinate matrices X.
From this, the commutator of Lz and the coordinate matrices X, Y, Z can be read off,
[
L
z
,
X
]
=
i
Y
,
[
L
z
,
Y
]
=
−
i
X
.
{\displaystyle {\begin{aligned}\left[L_{z},X\right]&=iY\,,\\[1ex]\left[L_{z},Y\right]&=-iX\,.\end{aligned}}}
This means that the quantities X + iY and X − iY have a simple commutation rule,
[
L
z
,
X
+
i
Y
]
=
(
X
+
i
Y
)
,
[
L
z
,
X
−
i
Y
]
=
−
(
X
−
i
Y
)
.
{\displaystyle {\begin{aligned}\left[L_{z},X+iY\right]&=(X+iY)\,,\\[1ex]\left[L_{z},X-iY\right]&=-(X-iY)\,.\end{aligned}}}
Just like the matrix elements of X + iP and X − iP for the harmonic oscillator Hamiltonian, this commutation law implies that these operators only have certain off diagonal matrix elements in states of definite m,
L
z
(
(
X
+
i
Y
)
|
m
⟩
)
=
(
X
+
i
Y
)
L
z
|
m
⟩
+
(
X
+
i
Y
)
|
m
⟩
=
(
m
+
1
)
(
X
+
i
Y
)
|
m
⟩
{\displaystyle L_{z}{\bigl (}(X+iY)|m\rangle {\bigr )}=(X+iY)L_{z}|m\rangle +(X+iY)|m\rangle =(m+1)(X+iY)|m\rangle }
meaning that the matrix (X + iY) takes an eigenvector of Lz with eigenvalue m to an eigenvector with eigenvalue m + 1. Similarly, (X − iY) decrease m by one unit, while Z does not change the value of m.
So, in a basis of |l,m⟩ states where L2 and Lz have definite values, the matrix elements of any of the three components of the position are zero, except when m is the same or changes by one unit.
This places a constraint on the change in total angular momentum. Any state can be rotated so that its angular momentum is in the z-direction as much as possible, where m = l. The matrix element of the position acting on |l,m⟩ can only produce values of m which are bigger by one unit, so that if the coordinates are rotated so that the final state is |l′,l′⟩, the value of l′ can be at most one bigger than the biggest value of l that occurs in the initial state. So l′ is at most l + 1.
The matrix elements vanish for l′ > l + 1, and the reverse matrix element is determined by Hermiticity, so these vanish also when l′ < l − 1: Dipole transitions are forbidden with a change in angular momentum of more than one unit.
=== Sum rules ===
The Heisenberg equation of motion determines the matrix elements of P in the Heisenberg basis from the matrix elements of X.
P
i
j
=
m
d
d
t
X
i
j
=
i
m
(
E
i
−
E
j
)
X
i
j
,
{\displaystyle P_{ij}=m{\frac {d}{dt}}X_{ij}=im\left(E_{i}-E_{j}\right)X_{ij}\,,}
which turns the diagonal part of the commutation relation into a sum rule for the magnitude of the matrix elements:
∑
j
P
i
j
x
j
i
−
X
i
j
p
j
i
=
i
∑
j
2
m
(
E
i
−
E
j
)
|
X
i
j
|
2
=
i
.
{\displaystyle \sum _{j}P_{ij}x_{ji}-X_{ij}p_{ji}=i\sum _{j}2m\left(E_{i}-E_{j}\right)\left|X_{ij}\right|^{2}=i\,.}
This yields a relation for the sum of the spectroscopic intensities to and from any given state, although to be absolutely correct, contributions from the radiative capture probability for unbound scattering states must be included in the sum:
∑
j
2
m
(
E
i
−
E
j
)
|
X
i
j
|
2
=
1
.
{\displaystyle \sum _{j}2m\left(E_{i}-E_{j}\right)\left|X_{ij}\right|^{2}=1\,.}
== See also ==
Interaction picture
Bra–ket notation
Introduction to quantum mechanics
Heisenberg's entryway to matrix mechanics
== References ==
== Further reading ==
Bernstein, Jeremy (2005). "Max Born and the quantum theory". American Journal of Physics. 73 (11). American Association of Physics Teachers (AAPT): 999–1008. Bibcode:2005AmJPh..73..999B. doi:10.1119/1.2060717. ISSN 0002-9505.
Max Born The statistical interpretation of quantum mechanics. Nobel Lecture – December 11, 1954.
Nancy Thorndike Greenspan, "The End of the Certain World: The Life and Science of Max Born" (Basic Books, 2005) ISBN 0-7382-0693-8. Also published in Germany: Max Born - Baumeister der Quantenwelt. Eine Biographie (Spektrum Akademischer Verlag, 2005), ISBN 3-8274-1640-X.
Max Jammer The Conceptual Development of Quantum Mechanics (McGraw-Hill, 1966)
Jagdish Mehra and Helmut Rechenberg The Historical Development of Quantum Theory. Volume 3. The Formulation of Matrix Mechanics and Its Modifications 1925–1926. (Springer, 2001) ISBN 0-387-95177-6
B. L. van der Waerden, editor, Sources of Quantum Mechanics (Dover Publications, 1968) ISBN 0-486-61881-1
Aitchison, Ian J. R.; MacManus, David A.; Snyder, Thomas M. (2004). "Understanding Heisenberg's "magical" paper of July 1925: A new look at the calculational details". American Journal of Physics. 72 (11). American Association of Physics Teachers (AAPT): 1370–1379. arXiv:quant-ph/0404009. doi:10.1119/1.1775243. ISSN 0002-9505. S2CID 53118117.
Thomas F. Jordan, Quantum Mechanics in Simple Matrix Form, (Dover publications, 2005) ISBN 978-0486445304
Merzbacher, E (1968). "Matrix methods in quantum mechanics". Am. J. Phys. 36 (9): 814–821. doi:10.1119/1.1975154.
== External links ==
An Overview of Matrix Mechanics
Matrix Methods in Quantum Mechanics
Heisenberg Quantum Mechanics Archived 2010-02-16 at the Wayback Machine (The theory's origins and its historical developing 1925–27)
Werner Heisenberg 1970 CBC radio Interview
On Matrix Mechanics at MathPages | Wikipedia/Matrix_Mechanics |
"Sickle Cell Anemia, a Molecular Disease" is a 1949 scientific paper by Linus Pauling, Harvey A. Itano, Seymour J. Singer and Ibert C. Wells that established sickle-cell anemia as a genetic disease in which affected individuals have a different form of the metalloprotein hemoglobin in their blood. The paper, published in the November 25, 1949 issue of Science, reports a difference in electrophoretic mobility between hemoglobin from healthy individuals and those with sickle-cell anemia, with those with sickle cell trait having a mixture of the two types. The paper suggests that the difference in electrophoretic mobility is probably due to a different number of ionizable amino acid residues in the protein portion of hemoglobin (which was confirmed in 1956 by Vernon Ingram), and that this change in molecular structure is responsible for the sickling process. It also reports the genetic basis for the disease, consistent with the simultaneous genealogical study by James V. Neel: those with sickle-cell anemia are homozygous for the disease gene, while heterozygous individuals exhibit the usually asymptomatic condition of sickle cell trait.
The paper introduced the concept of a "molecular disease", and is considered a major impetus to the development of molecular medicine. The paper helped establish that genes control not just the presence or absence of enzymes (as genetics had shown in the early 1940s) but also the specific structure of protein molecules. It was also an important triumph in the efforts of Pauling and others to apply the instruments and methods of the physical sciences to biology, and Pauling used it promote such research and attract funding.
== Caltech work ==
Linus Pauling was a prominent physical chemist at the California Institute of Technology (a main focal point of Warren Weaver's efforts to promote what he called "molecular biology" through Rockefeller Foundation grants). In the mid-1930s, Pauling turned his attention to the physical and chemical nature of hemoglobin. In 1946, he set graduate student Harvey Itano (who had been previously trained as a physician) the task of finding differences in hemoglobin that might explain sickle cell disease. After failing to find any differences in size, weight, or acid-base titration (despite the advanced instruments available at Caltech), Itano found that oxygen could inhibit the sickling process while various reducing agents could speed it up; this was the basis of Pauling and Itano's first publication on the disease. Itano also found that the globin portion of sickle cell hemoglobin had a barely detectable difference in electrical charge.
To measure this electrical difference precisely, Pauling assigned graduate student John Singer to work with Itano and another medical researcher, Ibert C. Wells, before Pauling left in early 1948 for a guest lectureship in England. Using a "Tiselius Apparatus" to perform free-boundary electrophoresis, Pauling's three researchers were able to estimate that molecules of sickle-cell hemoglobin had about three more positive charges than normal hemoglobin. They also estimated that blood from those with sickle cell trait was a mixture of 60 percent normal hemoglobin and 40 percent sickle-cell hemoglobin. Near the end of the project, they learned of parallel results by geneticist James V. Neel, who demonstrated the inheritance pattern of the disease by traditional genetic methods; both Neel's work and that of Pauling's group were published in the same issue of Science.
== Follow-up work ==
Following the 1949 paper, Itano left the Pauling laboratory to work with Neel; in the following years Itano and Neel used electrophoresis to identify a number of other human hemoglobin variants, including some associated with other diseases. At Caltech, a comparison of the amino acid content of normal and sickle cell hemoglobins showed that there were several differences in chemical makeup, but did not explain the difference in electric charge that made electrophoretic separation possible. The cause of this difference was pinpointed in 1956 and 1957, when Vernon Ingram used protein fingerprinting (a combination of electrophoresis and chromatography) to show that the key difference between normal hemoglobins and sickle cell hemoglobins was a single difference in one chain of the protein: a glutamic acid residue on the normal hemoglobin in place of a valine residue on the sickle cell hemoglobin.
The molecular disease concept put forward in the 1949 paper also became the basis for Linus Pauling's view of evolution. In the 1960s, by which time it had been shown that sickle cell trait confers resistance to malaria and so the gene had both positive and negative effects and demonstrated heterozygote advantage, Pauling suggested that molecular diseases were actually the basis of evolutionary change. He also advocated eugenic policies, such as marking all who carry the sickle cell trait and other molecular disease genes, to reduce the number of children born with genetic diseases.
== Notes and references ==
== External links ==
It's in the Blood! A Documentary History of Linus Pauling, Hemoglobin and Sickle Cell Anemia — Oregon State University Library
Sickle Cell Anemia, a Molecular Disease — reproduction of the paper | Wikipedia/Sickle_Cell_Anemia,_a_Molecular_Disease |
A solvated electron is a free electron in a solution, in which it behaves like an anion. An electron's being solvated in a solution means it is bound by the solution. The notation for a solvated electron in formulas of chemical reactions is "e−". Often, discussions of solvated electrons focus on their solutions in ammonia, which are stable for days, but solvated electrons also occur in water and many other solvents – in fact, in any solvent that mediates outer-sphere electron transfer. The solvated electron is responsible for a great deal of radiation chemistry.
== Ammonia solutions ==
Liquid ammonia will dissolve all of the alkali metals and other electropositive metals such as Ca, Sr, Ba, Eu, and Yb (also Mg using an electrolytic process), giving characteristic blue solutions. For alkali metals in liquid ammonia, the solution is blue when dilute and copper-colored when more concentrated (> 3 molar). These solutions conduct electricity. The blue colour of the solution is due to ammoniated electrons, which absorb energy in the visible region of light. The diffusivity of the solvated electron in liquid ammonia can be determined using potential-step chronoamperometry.
Solvated electrons in ammonia are the anions of salts called electrides.
Na + 6 NH3 → [Na(NH3)6]+ + e−
The reaction is reversible: evaporation of the ammonia solution produces a film of metallic sodium.
=== Case study: Li in NH3 ===
A lithium–ammonia solution at −60 °C is saturated at about 15 mol% metal (MPM). When the concentration is increased in this range electrical conductivity increases from 10−2 to 104 Ω−1cm−1 (larger than liquid mercury). At around 8 MPM, a "transition to the metallic state" (TMS) takes place (also called a "metal-to-nonmetal transition" (MNMT)). At 4 MPM a liquid-liquid phase separation takes place: the less dense gold-colored phase becomes immiscible from a denser blue phase. Above 8 MPM the solution is bronze/gold-colored. In the same concentration range the overall density decreases by 30%.
== Other solvents ==
Alkali metals also dissolve in some small primary amines, such as methylamine and ethylamine and hexamethylphosphoramide, forming blue solutions. Tetrahydrofuran (THF) dissolves alkali metal, but a Birch reduction (see § Applications) analogue does not proceed without a diamine ligand. Solvated electron solutions of the alkaline earth metals magnesium, calcium, strontium and barium in ethylenediamine have been used to intercalate graphite with these metals.
== Water ==
Solvated electrons are involved in the reaction of alkali metals with water, even though the solvated electron has only a fleeting existence. Below pH = 9.6 the hydrated electron reacts with the hydronium ion giving atomic hydrogen, which in turn can react with the hydrated electron giving hydroxide ion and usual molecular hydrogen H2.
Solvated electrons can be found even in the gas phase. This implies their possible existence in the upper atmosphere of Earth and involvement in nucleation and aerosol formation.
Its standard electrode potential value is −2.88 V. The equivalent conductivity of 177 Mho cm2 is similar to that of hydroxide ion. This value of equivalent conductivity corresponds to a diffusivity of 4.75
×
10
−
5
{\displaystyle \times 10^{-5}}
cm2s−1.
== Reactivity ==
Although quite stable, the blue ammonia solutions containing solvated electrons degrade rapidly in the presence of catalysts to give colorless solutions of sodium amide:
2 [Na(NH3)6]+e− → H2 + 2 NaNH2 + 10 NH3
Electride salts can be isolated by the addition of macrocyclic ligands such as crown ether and cryptands to solutions containing solvated electrons. These ligands strongly bind the cations and prevent their re-reduction by the electron.
[Na(NH3)6]+e− + cryptand → [Na(cryptand)]+e−+ 6 NH3
The solvated electron reacts with oxygen to form a superoxide radical (O2.−). With nitrous oxide, solvated electrons react to form nitroxyl radicals (NO.).
== Uses ==
Solvated electrons are involved in electrode processes, a broad area with many technical applications (electrosynthesis, electroplating, electrowinning).
A specialized use of sodium-ammonia solutions is the Birch reduction. Other reactions where sodium is used as a reducing agent also are assumed to involve solvated electrons, e.g. the use of sodium in ethanol as in the Bouveault–Blanc reduction.
Work by Cullen et al. showed that metal-ammonia solutions can be used to intercalate a range of layered materials, which can then be exfoliated in polar, aprotic solvents, to produce ionic solutions of two-dimensional materials. An example of this is the intercalation of graphite with potassium and ammonia, which is then exfoliated by spontaneous dissolution in THF to produce a graphenide solution.
== History ==
The observation of the color of metal-electride solutions is generally attributed to Humphry Davy. In 1807–1809, he examined the addition of grains of potassium to gaseous ammonia (liquefaction of ammonia was invented in 1823). James Ballantyne Hannay and J. Hogarth repeated the experiments with sodium in 1879–1880. W. Weyl in 1864 and C. A. Seely in 1871 used liquid ammonia, whereas Hamilton Cady in 1897 related the ionizing properties of ammonia to that of water. Charles A. Kraus measured the electrical conductance of metal ammonia solutions and in 1907 attributed it to the electrons liberated from the metal. In 1918, G. E. Gibson and W. L. Argo introduced the solvated electron concept. They noted based on absorption spectra that different metals and different solvents (methylamine, ethylamine) produce the same blue color, attributed to a common species, the solvated electron. In the 1970s, solid salts containing electrons as the anion were characterized.
== References ==
== Further reading == | Wikipedia/Hydrated_electron |
In medicinal chemistry, Drug Permeability is an empirical parameter that indicates how quickly a chemical entity or an active pharmaceutical ingredient crosses a biological membrane or another biological barrier to become bioavailable in the body. Drug permeability, together with drug aqueous solubility are the two parameters that define the fate of the active ingredient after oral administration and ultimately define its bioavailability. When drug permeability is empirically measured in vitro, it is generally called apparent permeability (Papp) as its absolute value varies according to the method selected for its measurement. Papp is measured in vitro utilizing cellular based barriers such as the Caco-2 model or utilizing artificial biomimetic barriers, such as the Parallel Artificial Membrane Permeation Assay (PAMPA) or the PermeaPad. All these methods are built on an acceptor compartment (from 0.2 up to several mL according to the method uses) where the drug solution is placed, a biomimetic barrier and an acceptor compartment, where the drug concentration is quantified over time. By maintaining sink condition, a steady state is reached after a lag time (τ, Fig. 1) .
== Data Analysis ==
The drug flux represents the slope of the linear regression of the accumulated mass (Q) over time (t) normalized over the permeation area (A), i.e., the surface area of the barrier available for permeation.
Equation 1:
j
=
d
Q
/
d
t
∗
1
/
A
{\displaystyle j=dQ/dt*1/A}
The drug apparent permeability (Papp) is calculated by normalizing the drug flux (j) over the initial concentration of the API in the donor compartment (c0) as:
Equation 2:
P
a
p
p
=
j
/
c
0
{\displaystyle P_{app}=j/c_{0}}
Dimensionally, the Papp represents a velocity, and it is normally expressed in cm/sec. The highest is the permeability, the highest is expected to be the bioavailability of the drug after oral administration.
== See also ==
Lipinski's rule of five
Pharmacodynamics
Pharmacokinetics
== References ==
== External links ==
Permm server and database, a computational tool for theoretical assessment of passive permeability of molecules across the lipid bilayer | Wikipedia/Drug_permeability |
A metal ion in aqueous solution or aqua ion is a cation, dissolved in water, of chemical formula [M(H2O)n]z+. The solvation number, n, determined by a variety of experimental methods is 4 for Li+ and Be2+ and 6 for most elements in periods 3 and 4 of the periodic table. Lanthanide and actinide aqua ions have higher solvation numbers (often 8 to 9), with the highest known being 11 for Ac3+. The strength of the bonds between the metal ion and water molecules in the primary solvation shell increases with the electrical charge, z, on the metal ion and decreases as its ionic radius, r, increases. Aqua ions are subject to hydrolysis. The logarithm of the first hydrolysis constant is proportional to z2/r for most aqua ions.
The aqua ion is associated, through hydrogen bonding with other water molecules in a secondary solvation shell. Water molecules in the first hydration shell exchange with molecules in the second solvation shell and molecules in the bulk liquid. The residence time of a molecule in the first shell varies among the chemical elements from about 100 picoseconds to more than 200 years. Aqua ions are prominent in electrochemistry.
== Introduction to metal aqua ions ==
* No experimental information regarding aqua ion structures
Most chemical elements are metallic. Compounds of the metallic elements usually form simple aqua ions with the formula [M(H2O)n]z+ in low oxidation states. With the higher oxidation states the simple aqua ions dissociate losing hydrogen ions to yield complexes that contain both water molecules and hydroxide or oxide ions, such as the vanadium(IV) species [VO(H2O)5]2+. In the highest oxidation states only oxyanions, such as the permanganate(VII) ion, MnO−4, are known. A few metallic elements that are commonly found only in high oxidation states, such as niobium and tantalum, are not known to form aqua cations; near the metal–nonmetal boundary, arsenic and tellurium are only known as hydrolysed species. Some elements, such as tin and antimony, are clearly metals, but form only covalent compounds in the highest oxidation states: their aqua cations are restricted to their lower oxidation states. Germanium is a semiconductor rather than a metal, but appears to form an aqua cation; similarly, hydrogen forms an aqua cation like metals, despite being a gas. The transactinides have been greyed out due to a lack of experimental data. For some highly radioactive elements, experimental chemistry has been done, and aqua cations may have been formed, but no experimental information is available regarding the structure of those putative aqua ions.
In aqueous solution the water molecules directly attached to the metal ion are said to belong to the first coordination sphere, also known as the first, or primary, solvation shell. The bond between a water molecule and the metal ion is a dative covalent bond, with the oxygen atom donating both electrons to the bond. Each coordinated water molecule may be attached by hydrogen bonds to other water molecules. The latter are said to reside in the second coordination sphere. The second coordination sphere is not a well defined entity for ions with charge 1 or 2. In dilute solutions it merges into the water structure in which there is an irregular network of hydrogen bonds between water molecules. With tripositive ions the high charge on the cation polarizes the water molecules in the first solvation shell to such an extent that they form strong enough hydrogen bonds with molecules in the second shell to form a more stable entity.
The strength of the metal-oxygen bond can be estimated in various ways. The hydration enthalpy, though based indirectly on experimental measurements, is the most reliable measure. The scale of values is based on an arbitrarily chosen zero, but this does not affect differences between the values for two metals. Other measures include the M–O vibration frequency and the M–O bond length. The strength of the M-O bond tends to increase with the charge and decrease as the size of the metal ion increases. In fact there is a very good linear correlation between hydration enthalpy and the ratio of charge squared to ionic radius, z2/r. For ions in solution Shannon's "effective ionic radius" is the measure most often used.
Water molecules in the first and second solvation shells can exchange places. The rate of exchange varies enormously, depending on the metal and its oxidation state. Metal aqua ions are always accompanied in solution by solvated anions, but much less is known about anion solvation than about cation solvation.
Understanding of the nature of aqua ions is helped by having information on the nature of solvated cations in mixed solvents and non-aqueous solvents, such as liquid ammonia, methanol, dimethyl formamide and dimethyl sulfoxide to mention a few.
== Occurrence in nature ==
Aqua ions are present in most natural waters. Na+, K+, Mg2+ and Ca2+ are major constituents of seawater.
Many other aqua ions are present in seawater in concentrations ranging from ppm to ppt. The concentrations of sodium, potassium, magnesium and calcium in blood are similar to those of seawater. Blood also has lower concentrations of essential elements such as iron and zinc. Sports drink is designed to be isotonic and also contains the minerals which are lost in perspiration.
Magnesium and calcium ions are common constituents of domestic water and are responsible for permanent and temporary hardness, respectively. They are often found in mineral water.
== Experimental methods ==
Information obtained on the nature of ions in solution varies with the nature of the experimental method used. Some methods reveal properties of the cation directly, others reveal properties that depend on both cation and anion. Some methods supply information of a static nature, a kind of snapshot of average properties, others give information about the dynamics of the solution.
=== Nuclear magnetic resonance (NMR) ===
Ions for which the water-exchange rate is slow on the NMR time-scale give separate peaks for molecules in the first solvation shell and for other water molecules. The solvation number is obtained as a ratio of peak areas. Here it refers to the number of water molecules in the first solvation shell. Molecules in the second solvation shell exchange rapidly with solvent molecules, giving rise to a small change in the chemical shift value of un-coordinated water molecules from that of water itself. The main disadvantage of this method is that it requires fairly concentrated solutions, with the associated risk of ion-pair formation with the anion.
=== X-ray diffraction (XRD) ===
A solution containing an aqua ion does not have the long-range order that would be present in a crystal containing the same ion, but there is short-range order. X-ray diffraction on solutions yields a radial distribution function from which the coordination number of the metal ion and metal-oxygen distance may be derived. With aqua ions of high charge some information is obtained about the second solvation shell.
This technique requires the use of relatively concentrated solutions. X-rays are scattered by electrons, so scattering power increases with atomic number. This makes hydrogen atoms all but invisible to X-ray scattering.
Large angle X-ray scattering has been used to characterize the second solvation shell with trivalent ions such as Cr3+ and Rh3+. The second hydration shell of Cr3+ was found to have 13±1 molecules at an average distance of 402±20 pm. This implies that every molecule in the first hydration shell is hydrogen bonded to two molecules in the second shell.
=== Neutron diffraction ===
Diffraction by neutrons also give a radial distribution function. In contrast to X-ray diffraction, neutrons are scattered by nuclei and there is no relationship with atomic number. Indeed, use can be made of the fact that different isotopes of the same element can have widely different scattering powers. In a classic experiment, measurements were made on four nickel chloride solutions using the combinations of 58Ni, 60Ni, 35Cl and 37Cl isotopes to yield a very detailed picture of cation and anion solvation. Data for a number of metal salts show some dependence on the salt concentration.
†Figures in brackets are standard deviations on the last significant figure of the value.‡ angle between a M-OH2 bond and the plane of the water molecule.
Most of these data refer to concentrated solutions in which there are very few water molecules that are not in the primary hydration spheres of the cation or anion, which may account for some of the variation of solvation number with concentration even if there is no contact ion pairing. The angle θ gives the angle of tilt of the water molecules relative to a plane in the aqua ion. This angle is affected by the hydrogen bonds formed between water molecules in the primary and secondary solvation shells.
The measured solvation number is a time-averaged value for the solution as a whole. When a measured primary solvation number is fractional there are two or more species with integral solvation numbers present in equilibrium with each other. This also applies to solvation numbers that are integral numbers, within experimental error. For example, the solvation number of 5.5 for a lithium chloride solution could be interpreted as being due to presence of two different aqua ions with equal concentrations.
[Li(H2O)6]+ ⇌ [Li(H2O)5]+ + H2O
Another possibility is that there is interaction between a solvated cation and an anion, forming an ion pair. This is particularly relevant when measurements are made on concentrated salt solutions. For example, a solvation number of 3 for a lithium chloride solution could be interpreted as being due to the equilibrium
[Li(H2O)4]+ + Cl− ⇌ [Li(H2O)3Cl] + H2O
lying wholly in favour of the ion pair.
=== Vibrational spectra ===
Infrared spectra and Raman spectra can be used to measure the M-O stretching frequency in metal aqua ions. Raman spectroscopy is particularly useful because the Raman spectrum of water is weak whereas the infrared spectrum of water is intense. Interpretation of the vibration frequencies is somewhat complicated by the presence, in octahedral and tetrahedral ions, of two vibrations, a symmetric one measured in the Raman spectrum and an anti-symmetric one, measured in the infrared spectrum.
Although the relationship between vibration frequency and force constant is not simple, the general conclusion that can be taken from these data is that the strength of the M-O bond increases with increasing ionic charge and decreasing ionic size. The M-O stretching frequency of an aqua ion in solution may be compared with its counterpart in a crystal of known structure. If the frequencies are very similar it can be concluded that the coordination number of the metal ion is the same in solution as it is in a compound in the solid state.
=== Dynamic methods ===
Data such as conductivity, electrical mobility and diffusion relate to the movement of ions through a solution. When an ion moves through a solution it tends to take both first and second solvation shells with it. Hence solvation numbers measured from dynamic properties tend to be much higher that those obtained from static properties.
== Solvation numbers and structures ==
=== Hydrogen ===
Hydrogen is not a metal, but like them it tends to lose its valence electron in chemical reactions, forming a cation H+. In aqueous solution, this immediately attaches itself to a water molecule, forming a species generally symbolised as H3O+ (sometimes loosely written H+). Such hydration forms cations that can in essence be considered as [H(OH2)n]+.
The solvation of H+ in water is not fully characterised and many different structures have been suggested. Two well-known structures are the Zundel cation and the Eigen cation. The Eigen solvation structure has the hydronium ion at the center of an H9O+4 complex in which the hydronium is strongly hydrogen-bonded to three neighbouring water molecules. In the Zundel H5O+2 complex the proton is shared equally by two water molecules in a symmetric hydrogen bond.
=== Alkali metals ===
The hydrated lithium cation in water is probably tetrahedral and four-coordinated. There are most probably six water molecules in the primary solvation sphere of the octahedral sodium ion. Potassium is seven-coordinate, and rubidium and caesium are probably eight-coordinate square antiprismatic. No data is available for francium.
=== Alkaline earth metals ===
§ Values extrapolated from data for solid-state crystal structures
The beryllium cation [Be(H2O)4]2+ has a very well-defined primary solvation shell with a tetrahedral BeO4 core. For magnesium, [Mg(H2O)6]2+ is also a well-characterized species, with an octahedral MgO6 core. The situation for calcium is more complicated. Neutron diffraction data gave a solvation number for calcium chloride, CaCl2, which is strongly dependent on concentration: 10.0±0.6 at 1 mol·dm−3, decreasing to 6.4±0.3 at 2.8 mol·dm−3. The enthalpy of solvation decreases with increasing ionic radius. Various solid hydrates are known with 8-coordination in square antiprism and dodecahedral geometry. In water, calcium and strontium are most probably eight-coordinate square antiprismatic (although seven-coordination for calcium cannot presently be excluded). Barium is not as well-studied: it seems to have a coordination number of either eight or nine. Theoretical simulation of radium suggests that its aqua cation is ten-coordinate.
=== Group 3 metals, lanthanides and actinides ===
Scandium(III) and yttrium(III) are both eight-coordinate, but have different structures: scandium has an unusual dicapped triangular prismatic structure (with one cap location empty), while yttrium is square antiprismatic. Lutetium(III) is tricapped triangular prismatic, but has a significant water deficit: one of the capping water molecules is significantly closer to the lutetium than the remaining ones and the average coordination number is only 8.2 rather than 9. Based on its ionic radius, lawrencium(III) is probably nine-coordinate tricapped triangular prismatic with no water deficit.
The trivalent lanthanide ions decrease steadily in size from lanthanum to lutetium, an effect known as the lanthanide contraction. From lanthanum to dysprosium, the coordination number is maintained at 9 with a tricapped trigonal prismatic structure, although starting from samarium the capping water molecules are no longer equally strongly bounded. A water deficit then appears for holmium through lutetium with the average coordination number dropping to 8.2 at lutetium(III). The configuration is maintained despite the small size of the cations and the water deficit, probably due to strong hydrogen bonding. Europium(II) is seven-coordinate, and cerium(IV) is hydrolysed to the oxygen-bridged dimer [(H2O)7Ce–O–Ce(OH2)7]6+.
Actinium(III) is eleven-coordinate in aqueous solution. Thorium(IV) is nine-coordinate tricapped trigonal prismatic, and it is assumed that the same is true for the other actinide(IV) cations in aqueous solutions (as that is also their solid-state configuration). Studies on coordination number and/or structure for actinides(III) to date stretch only to californium. However, since lawrencium(III) has a similar ionic radius to dysprosium(III), it is likely that uranium(III) through lawrencium(III) are all nine-coordinate tricapped triangular prismatic with the capping positions fully occupied. No data is available for fermium(II), mendelevium(II), or nobelium(II).
=== Group 4-12 metals ===
The ions of these metals in the +2 and +3 oxidation states have a solvation number of 6. All have a regular octahedral structure except the aqua ions of chromium(II) and copper(II) which are subject to Jahn-Teller distortion. In the copper case the two axial Cu−O distances are 238 pm, whereas the four equatorial Cu−O distances are 195 pm in the solid state. However, it is unclear whether Cu2+ has a solvation number of 5 or 6 in aqueous solution, with conflicting experimental reports. The structure of cobalt(III) in aqueous solution has not been determined. Copper(I) is estimated to be four-coordinate tetrahedral.
A solvation number of 6 with an octahedral structure is well established for zinc(II) and cadmium(II) in dilute solutions. In concentrated solutions the Zn2+ ion may adopt a 4-coordinate, tetrahedral, structure, but the evidence is not conclusive because of the possibility of ion pairing and/or hydrolysis. The solvation number of mercury(II) is most likely to be 6. Zinc(II) is six-coordinate octahedral, but cadmium(II) may be in equilibrium between six- and seven-coordination. Mercury(II) is a pseudo-Jahn-Teller-distorted octahedron. The bis aqua structure of the mercury(I) ion, [(H2O)-Hg-Hg-(OH2)]+, found in solid compounds, is not the same as that found in solution which involves three water molecules coordinated to each mercury completing a distorted tetrahedral arrangement. Another aqua species in which there is a metal-metal bond is the molybdenum(II) species formulated as [(H2O)4Mo≣Mo(H2O)4]4+. Each molybdenum is surrounded by four water molecules in a square-planar arrangement, in a structure similar to that of the known structure of the chloro complex [Mo2Cl8]4−.
There are a few divalent and trivalent aqua ions of transition metals in the second and third transition series: ruthenium(II) and (III), rhodium(III), and iridium(III), all octahedral. (Ruthenium and iridium structures have only been examined in the solid state, but it is assumed that they are the same in aqueous solution.) Molybdenum(III) is questionable (and may be strongly hydrolyzed in aqueous solution), and molybdenum(II) dimerises with each molybdenum binding four water molecules. Palladium(II) and platinum(II) aqua ions were originally thought to be square planar, but are actually strongly tetragonally elongated square-pyramidal or octahedral with the extra one or two water molecules extremely loosely bound. The structure of silver(I) is disputed: it may be two-coordinate, or it may be four-coordinate with two extra very loosely bound water molecules. Gold(III) is four-coordinate square planar in the solid state, and it is assumed to have the same structure in aqueous solution. Distortion occurs for low-coordinate metals with strong covalent tendencies due to the second-order Jahn-Teller effect. With oxidation state 4, however, the only unhydrolyzed species are the square antiprismatic zirconium(IV), [Zr(H2O)8]4+, and hafnium(IV), [Hf(H2O)8]4+, and even they are extremely prone to hydrolysis. Such a zirconium cation is only formed in dilute solutions of ZrIV in strong acid, and in practice the cationic species encountered of zirconium and hafnium are polynuclear.
=== Group 13-18 elements ===
Boron is not a metal, and boron(III) is too acidic for an aqua ion to exist: deprotonation proceeds as far as boric acid, borates, and hydroxyborates. The aluminium(III) aqua ion, [Al(H2O)6]3+ is very well characterized in solution and the solid state. The AlO6 core has octahedral symmetry, point group Oh. The aqua ions of gallium(III), indium(III) and thallium(III) are also six-coordinate octahedral. The coordination geometry of thallium(I) is not experimentally known, but it is likely to be hemidirected with a large gap in the coordination sphere.
Silicon is likewise not a metal, and silicon(IV) is a strong enough acid to deprotonate bound OH−. Thus various forms of hydrated silica (silicic acid) form. There is some evidence that germanium(II) aqua ions can form in perchloric acid media. Quantum mechanical calculations suggests that the germanium(II) aqua ion shows extreme distortion of the first coordination sphere due to the high charge density and the stereochemically active lone pairs. The first shell is calculated to usually have a solvation number of 6, but numbers 4–7 are also possible and the shell splits into two with differing distances from the central Ge2+. However, germanium(II) is readily oxidised to germanium(IV), for which only hydrolyzed species are expected. The important germanium(IV) species are anionic oxo-hydroxo mixed species, thus displaying intermediate behaviour between silicon and tin: the major species appear to be [GeO(OH)3]− and the octameric [Ge8O16(OH)3]3−, with [GeO2(OH)2]2− occurring in smaller quantities. Tin(II) is 3-coordinate hemidirected with a very large gap in the coordination sphere of tin(II). The hydration number of lead(II) is not well-established and could be anywhere from five to seven. In practice these cations tend to be polynuclear. For tin(IV) and lead(IV) there are only hydrolyzed species.
Arsenic(III) is calculated to form hydrolyzed species only. The stable cationic arsenic(III) species in water is calculated to be [As(OH)2]+, though hydrolysis usually proceeds further to neutral and anionic species. Antimony(III) aqua ions may exist in dilute solutions of antimony(III) in concentrated acids. Quantum mechanical calculations reveal a solvation number of 8, with the first coordination sphere splitting into two hydration hemispheres with 4 water molecules each. Bismuth(III) is eight-coordinate square antiprismatic in aqueous solution, though in the solid state it is nine-coordinate tricapped triangular prismatic. Although the structures for thallium(I), germanium(II), tin(II), lead(II), and antimony(III) are affected by the lone pairs, this is not so for bismuth(III).
Selenium(IV) is mostly present as selenous acid (H2SeO3) below pH 2; at higher pH this deprotonates to HSeO3− and then SeO32−. Cationic tellurium(IV) appears to be [Te(OH)3]+; it predominates in dilute solutions below pH 2. Above pH 4, the dominating species becomes TeO(OH)3−, and above pH 8 it becomes TeO2(OH)22−. Polonium(IV) should be similar to tellurium(IV), though a little weaker, in its tendency towards hydrolysis. The structure of polonium(II) does not appear to have been studied.
The halogens, being strongly nonmetallic, prefer to form anions rather than cations in aqueous solution. Anion solvation is complicated because the water molecules point the other way: cations bind to the oxygen atom of water, with the hydrogens facing away, while anions prefer to bond asymmetrically to only one of the hydrogen atoms in a nearby water molecule. This results in significant water–water hydrogen bonding and network formation already within the first hydration shell, to an extent that does not occur for cation solvation. Such interactions are larger for the heavier and larger halides; the hydrogen bonding decreases in strength as one proceeds from iodide to fluoride, because of increasing negative charge on the water molecules, the increasing inductive effect stemming from the higher electric fields, and increasing geometrical strain for the hydrogen bonding. The rare and extremely radioactive astatine seems to be more metallic: a cationic astatine(I) species is inferred from trace-scale experiments in acidic solutions, and sometimes symbolised At+, but its structure has not been determined.
The noble gases do not react with water, but their solubility in water increases when going down the group. Argon atoms in water appear to have a first hydration shell composed of 16±2 water molecules at a distance of 280–540 pm, and a weaker second hydration shell is found out to 800 pm. Similar hydration spheres have been found for krypton and xenon atoms in water.
=== Oxo-aqua-cations ===
Some elements in oxidation states higher than 3 form stable, aquated, oxo ions. Well known examples are the vanadyl(IV) and uranyl(VI) ions. They can be viewed as particularly stable hydrolysis products in a hypothetical reaction such as
[V(H2O)6]4+ → [VO(H2O)5]2+ + 2H+
The vanadium has a distorted octahedral environment (point group C4v) of one oxide ion and 5 water molecules. Titanyl, TiO2+, has a similar structure. Vanadium(V) is believed to exist as the dioxo-ion [VO2(H2O)4]+ at pH less than 2, but the evidence for this ion depends on the formation of complexes, such as oxalate complexes which have been shown to have the VO+2 unit, with cis-VO bonds, in the solid state. The chromium(IV) ion [CrO(H2O)5]2+, similar to the vanadium ion has been proposed on the basis of indirect evidence.
The uranyl ion, UO2+2, has a trans structure. The aqua ion UO2+2(aq) has five water molecules in the plane perpendicular to the O-U-O axis in a pentagonal bipyramid structure, point group D5h. Neptunyl and plutonyl have the same structure. Nothing is known of actinide(V) structures.
== Thermodynamics ==
The main goal of thermodynamics in this context is to derive estimates of single-ion thermodynamic quantities such as hydration enthalpy and hydration entropy. These quantities relate to the reaction
Mz+ (gas) + solvent → Mz+ (in solution)
The enthalpy for this reaction is not directly measurable, because all measurements use salt solutions that contain both cation and anion. Most experimental measurements relate to the heat evolved when a salt dissolves in water, which gives the sum of cation and anion solvation enthalpies. Then, by considering the data for different anions with the same cation and different cations with the same anion, single ion values relative to an arbitrary zero, are derived.
Other values include Zn2+ -2044.3, Cd2+ -1805.8 and Ag+ -475.3 kJ mol−1.
There is an excellent linear correlation between hydration enthalpy and the ratio of charge squared, z2, to M-O distance, reff.
Δ
H
⊖
=
−
69500
z
2
/
r
e
f
f
{\displaystyle \Delta H^{\ominus }=-69500\ \mathrm {z^{2}/r_{eff}} }
Values for transition metals are affected by crystal field stabilization. The general trend is shown by the magenta line which passes through Ca2+, Mn2+ and Zn2+, for which there is no stabilization in an octahedral crystal field. Hydration energy increases as size decreases. Crystal field splitting confers extra stability on the aqua ion. The maximum crystal field stabilization energy occurs at Ni2+. The agreement of the hydration enthalpies with predictions provided one basis for the general acceptance of crystal field theory.
The hydration enthalpies of the trivalent lanthanide ions show an increasingly negative values at atomic number increases, in line with the decrease in ionic radius known as the lanthanide contraction.
Single ion hydration entropy can be derived. Values are shown in the following table. The more negative the value, the more there is ordering in forming the aqua ion. It is notable that the heavy alkali metals have rather small entropy values which suggests that both the first and second solvation shells are somewhat indistinct.
== Hydrolysis of aqua ions ==
There are two ways of looking at an equilibrium involving hydrolysis of an aqua ion. Considering the dissociation equilibrium
[M(H2O)n]z+ - H+⇌ [M(H2O)n-1(OH)](z-1)+
the activity of the hydrolysis product, omitting the water molecules, is given by
{
[
M
(
OH
)
]
(
z
−
1
)
+
}
=
K
1
,
−
1
{
M
z
+
}
{
H
+
}
−
1
{\displaystyle \{[{\ce {M(OH)}}]^{(z-1)+}\}=K_{1,-1}\{{\ce {M}}^{z+}\}\{{\ce {H}}^{+}\}^{-1}}
The alternative is to write the equilibrium as a complexation or substitution reaction
[M(H2O)n]z+ +OH− ⇌ :[M(H2O)n-1(OH)](z-1)+ + H2O
In which case
{
[
M
(
OH
)
]
(
z
−
1
)
+
}
=
K
1
,
1
{
M
z
+
}
{
OH
−
}
{\displaystyle \{[{\ce {M(OH)}}]^{(z-1)+}\}=K_{1,1}\{{\ce {M}}^{z+}\}\{{\ce {OH}}^{-}\}}
The concentration of hydrogen and hydroxide ions are related by the self-ionization of water, Kw = {H+} {OH−} so the two equilibrium constants are related as
K
1
,
−
1
=
K
1
,
1
×
K
w
{\displaystyle K_{1,-1}=K_{1,1}\times K_{w}}
In practice the first definition is more useful because equilibrium constants are determined from measurements of hydrogen ion concentrations. In general,
[
M
x
(
OH
)
y
]
=
β
x
,
−
y
∗
[
M
]
x
[
H
]
−
y
{\displaystyle [{\ce {M}}_{x}({\ce {OH}})_{y}]=\beta _{x,-y}*[{\ce {M}}]^{x}[{\ce {H}}]^{-y}}
charges are omitted for the sake of generality and activities have been replaced by concentrations.
β
∗
{\displaystyle \beta *}
are cumulative hydrolysis constants.
Modeling the hydrolysis reactions that occur in solution is usually based on the determination of equilibrium constants from potentiometric (pH) titration data. The process is far from straightforward for a variety of reasons. Sometimes the species in solution can be precipitated as salts and their structure confirmed by X-ray crystallography. In other cases, precipitated salts bear no relation to what is postulated to be in solution, because a particular crystalline substances may have both low solubility and very low concentration in the solutions.
=== First hydrolysis constant ===
The logarithm of hydrolysis constant, K1,-1, for the removal of one proton from an aqua ion
[M(H2O)n]z+ - H+ ⇌ [M(H2O)n-1(OH)](z-1)+
[ [M(OH)]{(z-1)+ ] = K1,-1 [Mz+] [H+] −1
shows a linear relationship with the ratio of charge to M-O distance, z/d. Ions fall into four groups. The slope of the straight line is the same for all groups, but the intercept, A, is different.
The cations most resistant to hydrolysis for their size and charge are hard pre-transition metal ions or lanthanide ions. The slightly less resistant group includes the transition metal ions. The third group contains mostly soft ions ion of post-transition metals. The ions which show the strongest tendency to hydrolyze for their charge and size are Pd2+, Sn2+ and Hg2+. This is because of the low coordination numbers of ions in this part of the periodic table (also including Ag+ and Au+), so that fewer water molecules are present around the cation and they experience more electrostatic force than normal. A similar situation affects Be2+, the smallest aqua cation, which is also more acidic than would normally be expected.
The standard enthalpy change for the first hydrolysis step is generally not very different from that of the dissociation of pure water. Consequently, the standard enthalpy change for the substitution reaction
[M(H2O)n]z+ +OH− ⇌ :[M(H2O)n-1(OH)](z-1)+ + H2O
is close to zero. This is typical of reactions between a hard cation and a hard anion, such as the hydroxide ion. It means that the standard entropy charge is the major contributor to the standard free energy change and hence the equilibrium constant.
Δ
G
⊖
=
−
R
T
ln
K
=
Δ
H
⊖
−
T
Δ
S
⊖
{\displaystyle \Delta G^{\ominus }=-RT\ln K=\Delta H^{\ominus }-T\Delta S^{\ominus }}
The change in ionic charge is responsible for the effect as the aqua ion has a greater ordering effect on the solution than the less highly charged hydroxo complex.
=== Multiple hydrolysis reactions ===
The hydrolysis of beryllium shows many of the characteristics typical of multiple hydrolysis reactions. The concentrations of various species, including polynuclear species with bridging hydroxide ions, change as a function of pH up to the precipitation of an insoluble hydroxide. Beryllium hydrolysis is unusual in that the concentration of [Be(H2O)3(OH)]+ is too low to be measured. Instead a trimer ([Be3(H2O)6(OH3))3+ is formed, whose structure has been confirmed in solid salts. The formation of polynuclear species is driven by the reduction in charge density within the molecule as a whole. The local environment of the beryllium ions approximates to [Be(H2O)2(OH)2]+. The reduction in effective charge releases free energy in the form of a decrease of the entropy of ordering at the charge centers.
The hydrolysis product of aluminium formulated as [Al13O4(OH)24(H2O)12]7+ is very well characterized and may be present in nature in water at pH ca. 5.4.
The overall reaction for the loss of two protons from an aqua ion can be written as
[M(H2O)n]z+ - 2 H+⇌ [M(H2O)n-2(OH)2](z-2)+
However, the equilibrium constant for the loss of two protons applies equally well to the equilibrium
[M(H2O)n]z+ - 2 H+⇌ [MO(H2O)n-2](z-2)+ + H2O
because the concentration of water is assumed to be constant. This applies in general: any equilibrium constant is equally valid for a product with an oxide ion as for the product with two hydroxyl ions. The two possibilities can only be distinguished by determining the structure of a salt in the solid state. Oxo bridges tend to occur when the metal oxidation state is high. An example is provided by the molybdenum(IV) complex [Mo3O4(H2O)9]4+ in which there is a triangle of molybdenum atoms joined by σ- bonds with an oxide bridge on each edge of the triangle and a fourth oxide which bridges to all three Mo atoms.
=== Oxyanions ===
There are very few oxo-aqua ions of metals in the oxidation state +5 or higher. Rather, the species found in aqueous solution are monomeric and polymeric oxyanions. Oxyanions can be viewed as the end products of hydrolysis, in which there are no water molecules attached to the metal, only oxide ions.
== Exchange kinetics ==
A water molecule in the first solvation shell of an aqua ion may exchange places with a water molecule in the bulk solvent. It is usually assumed that the rate-determining step is a dissociation reaction.
[M(H2O)n]z+ → [M(H2O)n-1]z+* + H2O
The * symbol signifies that this is the transition state in a chemical reaction. The rate of this reaction is proportional to the concentration of the aqua ion, [A].
r
a
t
e
=
−
(
d
[
A
]
d
t
)
T
=
k
[
A
]
{\displaystyle \mathrm {rate} =-\left({\frac {d[A]}{dt}}\right)_{T}=k[A]}
.
The proportionality constant, k, is called a first-order rate constant at temperature T. The unit of the reaction rate for water exchange is usually taken as mol dm−3s−1.
The half-life for this reaction is equal to loge2 / k. This quantity with the dimension of time is useful because it is independent of concentration. The quantity 1/k, also with dimension of time, equal to the half life divided by 0.6932, is known as the residence time or time constant.
The residence time for water exchange varies from about 10−10 s for Cs+ to about 10+10 s (more than 200 y) for Ir3+. It depends on factors such as the size and charge on the ion and, in the case of transition metal ions, crystal field effects. Very fast and very slow reactions are difficult to study. The most information on the kinetics a water exchange comes from systems with a residence time between about 1 μs and 1 s. The enthalpy and entropy of activation, ΔH‡ and ΔS‡ can be obtained by observing the variation of rate constant with temperature.
Note the general increase in the residence time from vanadium to nickel, which mirrors the decrease in ion size with increasing atomic number, which is a general trend in the periodic table, though given a specific name only in the case of the lanthanide contraction. The effects of crystal field stabilization energy are superimposed on the periodic trend.
Solvent exchange is generally slower for trivalent than for divalent ions, as the higher electrical charge on the cation makes for stronger M-OH2 bonds and, in consequence, higher activation energy for the dissociative reaction step, [M(H2O)n]3+ → [M(H2O)n-1]3+ + H2O. The values in the table show that this is due to both activation enthalpy and entropy factors.
The ion [Al(H2O)6]3+ is relatively inert to substitution reactions because its electrons are effectively in a closed shell electronic configuration, [Ne]3s23p6, making dissociation an energy-expensive reaction. Cr3+, which has an octahedral structure and a d3 electronic configuration is also relatively inert, as are Rh3+ and Ir3+ which have a low-spin d6 configuration.
== Formation of complexes ==
Metal aqua ions are often involved in the formation of complexes. The reaction may be written as
pMx+(aq) + qLy− → [MpLq](px-qy)+
In reality this is a substitution reaction in which one or more water molecules from the first hydration shell of the metal ion are replaced by ligands, L. The complex is described as an inner-sphere complex. A complex such as [ML](p-q)+ may be described as a contact ion pair.
When the water molecule(s) of the second hydration shell are replaced by ligands, the complex is said to be an outer-sphere complex, or solvent-shared ion pair. The formation of solvent-shared or contact ion pairs is particularly relevant to the determination of solvation numbers of aqua ions by methods that require the use of concentrated solutions of salts, as ion pairing is concentration-dependent. Consider, for example, the formation of the complex [MgCl]+ in solutions of MgCl2. The formation constant K of the complex is about 1 but varies with ionic strength. The concentration of the rather weak complex increases from about 0.1% for a 10mM solution to about 70% for a 1M solution (1M = 1 mol dm−3).
== Electrochemistry ==
The standard electrode potential for the half-cell equilibrium Mz+ + z e− ⇌ M(s) has been measured for all metals except for the heaviest trans-uranium elements.
As the standard electrode potential is more negative the aqua ion is more difficult to reduce. For example, comparing the potentials for zinc (-0.75 V) with those of iron (Fe(II) -0.47 V, Fe(III) -0.06 V) it is seen that iron ions are more easily reduced than zinc ions. This is the basis for using zinc to provide anodic protection for large structures made of iron or to protect small structures by galvanization.
== References ==
== Bibliography ==
Baes, C.F.; Mesmer, R.E. (1986) [1976]. The Hydrolysis of Cations. Malabar, FL: Robert E. Krieger. ISBN 978-0-89874-892-5.
Burgess, John (1978). Metal Ions in Solution. Chichester: Ellis Horwood. ISBN 978-0-85312-027-8.
Richens, David. T. (1997). The Chemistry of Aqua Ions. Wiley. ISBN 978-0-471-97058-3.
Stumm, Werner; Morgan, James J. (1995). Aquatic Chemistry - Chemical Equilibria and Rates in Natural Waters (3rd. ed.). Wiley-Blackwell. ISBN 978-0-471-51185-4.
Schweitzer, George K.; Pesterfield, Lester L. (2010). The Aqueous Chemistry of the Elements. Oxford: OUP. ISBN 978-0-19-539335-4.
== Further reading ==
H. L. Friedman, F. Franks, Aqueous Solutions of Simple Electrolytes, Springer; reprint of the 1973 edition, 2012 ISBN 1468429574 | Wikipedia/Metal_ions_in_aqueous_solution |
A chemical equation is the symbolic representation of a chemical reaction in the form of symbols and chemical formulas. The reactant entities are given on the left-hand side and the product entities are on the right-hand side with a plus sign between the entities in both the reactants and the products, and an arrow that points towards the products to show the direction of the reaction. The chemical formulas may be symbolic, structural (pictorial diagrams), or intermixed. The coefficients next to the symbols and formulas of entities are the absolute values of the stoichiometric numbers. The first chemical equation was diagrammed by Jean Beguin in 1615.
== Structure ==
A chemical equation (see an example below) consists of a list of reactants (the starting substances) on the left-hand side, an arrow symbol, and a list of products (substances formed in the chemical reaction) on the right-hand side. Each substance is specified by its chemical formula, optionally preceded by a number called stoichiometric coefficient. The coefficient specifies how many entities (e.g. molecules) of that substance are involved in the reaction on a molecular basis. If not written explicitly, the coefficient is equal to 1. Multiple substances on any side of the equation are separated from each other by a plus sign.
As an example, the equation for the reaction of hydrochloric acid with sodium can be denoted:
2HCl + 2Na → 2NaCl + H2
Given the formulas are fairly simple, this equation could be read as "two H-C-L plus two N-A yields two N-A-C-L and H two." Alternately, and in general for equations involving complex chemicals, the chemical formulas are read using IUPAC nomenclature, which could verbalise this equation as "two hydrochloric acid molecules and two sodium atoms react to form two formula units of sodium chloride and a hydrogen gas molecule."
=== Reaction types ===
Different variants of the arrow symbol are used to denote the type of a reaction:
=== State of matter ===
To indicate physical state of a chemical, a symbol in parentheses may be appended to its formula: (s) for a solid, (l) for a liquid, (g) for a gas, and (aq) for an aqueous solution. This is especially done when one wishes to emphasize the states or changes thereof. For example, the reaction of aqueous hydrochloric acid with solid (metallic) sodium to form aqueous sodium chloride and hydrogen gas would be written like this:
2HCl(aq) + 2Na(s) → 2NaCl(aq) + H2(g)
That reaction would have different thermodynamic and kinetic properties if gaseous hydrogen chloride were to replace the hydrochloric acid as a reactant:
2HCl(g) + 2Na(s) → 2NaCl(s) + H2(g)
Alternately, an arrow without parentheses is used in some cases to indicate formation of a gas ↑ or precipitate ↓. This is especially useful if only one such species is formed. Here is an example indicating that hydrogen gas is formed:
2HCl + 2Na → 2 NaCl + H2 ↑
=== Catalysis and other conditions ===
If the reaction requires energy, it is indicated above the arrow. A capital Greek letter delta (Δ) or a triangle (△) is put on the reaction arrow to show that energy in the form of heat is added to the reaction. The expression hν is used as a symbol for the addition of energy in the form of light. Other symbols are used for other specific types of energy or radiation.
Similarly, if a reaction requires a certain medium with certain specific characteristics, then the name of the acid or base that is used as a medium may be placed on top of the arrow. If no specific acid or base is required, another way of denoting the use of an acidic or basic medium is to write H+ or OH− (or even "acid" or "base") on top of the arrow. Specific conditions of the temperature and pressure, as well as the presence of catalysts, may be indicated in the same way.
=== Notation variants ===
The standard notation for chemical equations only permits all reactants on one side, all products on the other, and all stoichiometric coefficients positive. For example, the usual form of the equation for dehydration of methanol to dimethylether is:
2 CH3OH → CH3OCH3 + H2O
Sometimes an extension is used, where some substances with their stoichiometric coefficients are moved above or below the arrow, preceded by a plus sign or nothing for a reactant, and by a minus sign for a product. Then the same equation can look like this:
2
CH
3
OH
→
−
H
2
O
CH
3
OCH
3
{\displaystyle {\ce {2CH3OH->[{\overset {}{\ce {-H2O}}}]CH3OCH3}}}
Such notation serves to hide less important substances from the sides of the equation, to make the type of reaction at hand more obvious, and to facilitate chaining of chemical equations. This is very useful in illustrating multi-step reaction mechanisms. Note that the substances above or below the arrows are not catalysts in this case, because they are consumed or produced in the reaction like ordinary reactants or products.
Another extension used in reaction mechanisms moves some substances to branches of the arrow. Both extensions are used in the example illustration of a mechanism.
Use of negative stoichiometric coefficients at either side of the equation (like in the example below) is not widely adopted and is often discouraged.
2
CH
3
OH
−
H
2
O
⟶
CH
3
OCH
3
{\displaystyle {\ce {2 CH3OH \;-\; H2O -> CH3OCH3}}}
== Balancing chemical equations ==
Because no nuclear reactions take place in a chemical reaction, the chemical elements pass through the reaction unchanged. Thus, each side of the chemical equation must represent the same number of atoms of any particular element (or nuclide, if different isotopes are taken into account). The same holds for the total electric charge, as stated by the charge conservation law. An equation adhering to these requirements is said to be balanced.
A chemical equation is balanced by assigning suitable values to the stoichiometric coefficients. Simple equations can be balanced by inspection, that is, by trial and error. Another technique involves solving a system of linear equations.
Balanced equations are usually written with smallest natural-number coefficients. Yet sometimes it may be advantageous to accept a fractional coefficient, if it simplifies the other coefficients. The introductory example can thus be rewritten as
HCl
+
Na
⟶
NaCl
+
1
2
H
2
{\displaystyle {\ce {HCl + Na -> NaCl + 1/2 H2}}}
In some circumstances the fractional coefficients are even inevitable. For example, the reaction corresponding to the standard enthalpy of formation must be written such that one molecule of a single product is formed. This will often require that some reactant coefficients be fractional, as is the case with the formation of lithium fluoride:
Li
(
s
)
+
1
2
F
2
(
g
)
⟶
LiF
(
s
)
{\displaystyle {\ce {Li(s) + 1/2F2(g) -> LiF(s)}}}
=== Inspection method ===
The method of inspection can be outlined as setting the most complex substance's stoichiometric coefficient to 1 and assigning values to other coefficients step by step such that both sides of the equation end up with the same number of atoms for each element. If any fractional coefficients arise during this process, the presence of fractions may be eliminated (at any time) by multiplying all coefficients by their lowest common denominator.
Example
Balancing of the chemical equation for the complete combustion of methane
?
CH
4
+
?
O
2
⟶
?
CO
2
+
?
H
2
O
{\displaystyle {\ce {{\mathord {?}}\,{CH4}+{\mathord {?}}\,{O2}->{\mathord {?}}\,{CO2}+{\mathord {?}}\,{H2O}}}}
is achieved as follows:
A coefficient of 1 is placed in front of the most complex formula (CH4):
1
CH
4
+
?
O
2
⟶
?
CO
2
+
?
H
2
O
{\displaystyle {\ce {1{CH4}+{\mathord {?}}\,{O2}->{\mathord {?}}\,{CO2}+{\mathord {?}}\,{H2O}}}}
The left-hand side has 1 carbon atom, so 1 molecule of CO2 will balance it. The left-hand side also has 4 hydrogen atoms, which will be balanced by 2 molecules of H2O:
1
CH
4
+
?
O
2
⟶
1
CO
2
+
2
H
2
O
{\displaystyle {\ce {1{CH4}+{\mathord {?}}\,{O2}->1{CO2}+2H2O}}}
Balancing the 4 oxygen atoms of the right-hand side by 2 molecules of O2 yields the equation
1
CH
4
+
2
O
2
⟶
1
CO
2
+
2
H
2
O
{\displaystyle {\ce {1 CH4 + 2 O2 -> 1 CO2 + 2 H2O}}}
The coefficients equal to 1 are omitted, as they do not need to be specified explicitly:
CH
4
+
2
O
2
⟶
CO
2
+
2
H
2
O
{\displaystyle {\ce {CH4 + 2 O2 -> CO2 + 2 H2O}}}
It is wise to check that the final equation is balanced, i.e. that for each element there is the same number of atoms on the left- and right-hand side: 1 carbon, 4 hydrogen, and 4 oxygen.
=== System of linear equations ===
For each chemical element (or nuclide or unchanged moiety or charge) i, its conservation requirement can be expressed by the mathematical equation
∑
j
∈
reactants
a
i
j
s
j
=
∑
j
∈
products
a
i
j
s
j
{\displaystyle \sum _{j\,\in \,{\text{reactants}}}\!\!\!\!\!a_{ij}s_{j}\ =\!\!\!\!\!\sum _{j\,\in \,{\text{products}}}\!\!\!\!\!a_{ij}s_{j}}
where
aij is the number of atoms of element i in a molecule of substance j (per formula in the chemical equation), and
sj is the stoichiometric coefficient for the substance j.
This results in a homogeneous system of linear equations, which are readily solved using mathematical methods. Such system always has the all-zeros trivial solution, which we are not interested in, but if there are any additional solutions, there will be infinite number of them. Any non-trivial solution will balance the chemical equation. A "preferred" solution is one with whole-number, mostly positive stoichiometric coefficients sj with greatest common divisor equal to one.
==== Example ====
Let us assign variables to stoichiometric coefficients of the chemical equation from the previous section and write the corresponding linear equations:
s
1
CH
4
+
s
2
O
2
⟶
s
3
CO
2
+
s
4
H
2
O
{\displaystyle {\ce {{\mathit {s}}_{1}{CH4}+{\mathit {s}}_{2}{O2}->{\mathit {s}}_{3}{CO2}+{\mathit {s}}_{4}{H2O}}}}
C:
s
1
=
s
3
H:
4
s
1
=
2
s
4
O:
2
s
2
=
2
s
3
+
s
4
{\displaystyle \quad \;\;\;{\begin{aligned}{\text{C:}}&&s_{1}&=s_{3}\\{\text{H:}}&&4s_{1}&=2s_{4}\\{\text{O:}}&&2s_{2}&=2s_{3}+s_{4}\end{aligned}}}
All solutions to this system of linear equations are of the following form, where r is any real number:
s
1
=
r
s
2
=
2
r
s
3
=
r
s
4
=
2
r
{\displaystyle {\begin{aligned}s_{1}&=r\\s_{2}&=2r\\s_{3}&=r\\s_{4}&=2r\end{aligned}}}
The choice of r = 1 yields the preferred solution,
s
1
=
1
s
2
=
2
s
3
=
1
s
4
=
2
{\displaystyle {\begin{aligned}s_{1}&=1\\s_{2}&=2\\s_{3}&=1\\s_{4}&=2\end{aligned}}}
which corresponds to the balanced chemical equation:
CH
4
+
2
O
2
⟶
CO
2
+
2
H
2
O
{\displaystyle {\ce {CH4 + 2 O2 -> CO2 + 2 H2O}}}
=== Matrix method ===
The system of linear equations introduced in the previous section can also be written using an efficient matrix formalism. First, to unify the reactant and product stoichiometric coefficients sj, let us introduce the quantity
ν
j
=
{
−
s
j
for a reactant
+
s
j
for a product
{\displaystyle \nu _{j}={\begin{cases}-s_{j}&{\text{for a reactant}}\\+s_{j}&{\text{for a product}}\end{cases}}}
called stoichiometric number, which simplifies the linear equations to
∑
j
=
1
J
a
i
j
ν
j
=
0
{\displaystyle \sum _{j=1}^{J}a_{ij}\nu _{j}=0}
where J is the total number of reactant and product substances (formulas) in the chemical equation.
Placement of the values aij at row i and column j of the composition matrix
A =
[
a
1
,
1
a
1
,
2
⋯
a
1
,
J
a
2
,
1
a
2
,
2
⋯
a
2
,
J
⋮
⋮
⋱
⋮
]
{\displaystyle {\begin{bmatrix}a_{1,1}&a_{1,2}&\cdots &a_{1,J}\\a_{2,1}&a_{2,2}&\cdots &a_{2,J}\\\vdots &\vdots &\ddots &\vdots \end{bmatrix}}}
and arrangement of the stoichiometric numbers into the stoichiometric vector
ν =
[
ν
1
ν
2
⋮
ν
J
]
{\displaystyle {\begin{bmatrix}\nu _{1}\\\nu _{2}\\\vdots \\\nu _{J}\end{bmatrix}}}
allows the system of equations to be expressed as a single matrix equation:
Aν = 0
Like previously, any nonzero stoichiometric vector ν, which solves the matrix equation, will balance the chemical equation.
The set of solutions to the matrix equation is a linear space called the kernel of the matrix A. For this space to contain nonzero vectors ν, i.e. to have a positive dimension JN, the columns of the composition matrix A must not be linearly independent. The problem of balancing a chemical equation then becomes the problem of determining the JN-dimensional kernel of the composition matrix. It is important to note that only for JN = 1 will there be a unique preferred solution to the balancing problem. For JN > 1 there will be an infinite number of preferred solutions with JN of them linearly independent. If JN = 0, there will be only the unusable trivial solution, the zero vector.
Techniques have been developed to quickly calculate a set of JN independent solutions to the balancing problem, which are superior to the inspection and algebraic method in that they are determinative and yield all solutions to the balancing problem.
Example
Using the same chemical equation again, write the corresponding matrix equation:
s
1
CH
4
+
s
2
O
2
⟶
s
3
CO
2
+
s
4
H
2
O
{\displaystyle {\ce {{\mathit {s}}_{1}{CH4}+{\mathit {s}}_{2}{O2}->{\mathit {s}}_{3}{CO2}+{\mathit {s}}_{4}{H2O}}}}
C:
H:
O:
[
1
0
1
0
4
0
0
2
0
2
2
1
]
[
ν
1
ν
2
ν
3
ν
4
]
=
0
{\displaystyle {\begin{matrix}{\text{C:}}\\{\text{H:}}\\{\text{O:}}\end{matrix}}\quad {\begin{bmatrix}1&0&1&0\\4&0&0&2\\0&2&2&1\end{bmatrix}}{\begin{bmatrix}\nu _{1}\\\nu _{2}\\\nu _{3}\\\nu _{4}\end{bmatrix}}=\mathbf {0} }
Its solutions are of the following form, where r is any real number:
[
ν
1
ν
2
ν
3
ν
4
]
=
[
−
s
1
−
s
2
s
3
s
4
]
=
r
[
−
1
−
2
1
2
]
{\displaystyle {\begin{bmatrix}\nu _{1}\\\nu _{2}\\\nu _{3}\\\nu _{4}\end{bmatrix}}={\begin{bmatrix}-s_{1}\\-s_{2}\\s_{3}\\s_{4}\end{bmatrix}}=r{\begin{bmatrix}-1\\-2\\1\\2\end{bmatrix}}}
The choice of r = 1 and a sign-flip of the first two rows yields the preferred solution to the balancing problem:
[
−
ν
1
−
ν
2
ν
3
ν
4
]
=
[
s
1
s
2
s
3
s
4
]
=
[
1
2
1
2
]
{\displaystyle {\begin{bmatrix}-\nu _{1}\\-\nu _{2}\\\nu _{3}\\\nu _{4}\end{bmatrix}}={\begin{bmatrix}s_{1}\\s_{2}\\s_{3}\\s_{4}\end{bmatrix}}={\begin{bmatrix}1\\2\\1\\2\end{bmatrix}}}
== Ionic equations ==
An ionic equation is a chemical equation in which electrolytes are written as dissociated ions. Ionic equations are used for single and double displacement reactions that occur in aqueous solutions.
For example, in the following precipitation reaction:
CaCl
2
+
2
AgNO
3
⟶
Ca
(
NO
3
)
2
+
2
AgCl
↓
{\displaystyle {\ce {CaCl2 + 2AgNO3 -> Ca(NO3)2 + 2 AgCl(v)}}}
the full ionic equation is:
Ca
2
+
+
2
Cl
−
+
2
Ag
+
+
2
NO
3
−
⟶
Ca
2
+
+
2
NO
3
−
+
2
AgCl
↓
{\displaystyle {\ce {Ca^2+ + 2Cl^- + 2Ag+ + 2NO3^- -> Ca^2+ + 2NO3^- + 2AgCl(v)}}}
or, with all physical states included:
Ca
2
+
(
aq
)
+
2
Cl
−
(
aq
)
+
2
Ag
+
(
aq
)
+
2
NO
3
−
(
aq
)
⟶
Ca
2
+
(
aq
)
+
2
NO
3
−
(
aq
)
+
2
AgCl
↓
{\displaystyle {\ce {Ca^2+(aq) + 2Cl^{-}(aq) + 2Ag+(aq) + 2NO3^{-}(aq) -> Ca^2+(aq) + 2NO3^{-}(aq) + 2AgCl(v)}}}
In this reaction, the Ca2+ and the NO3− ions remain in solution and are not part of the reaction. That is, these ions are identical on both the reactant and product side of the chemical equation. Because such ions do not participate in the reaction, they are called spectator ions. A net ionic equation is the full ionic equation from which the spectator ions have been removed. The net ionic equation of the proceeding reactions is:
2
Cl
−
+
2
Ag
+
⟶
2
AgCl
↓
{\displaystyle {\ce {2Cl^- + 2Ag+ -> 2AgCl(v)}}}
or, in reduced balanced form,
Ag
+
+
Cl
−
⟶
AgCl
↓
{\displaystyle {\ce {Ag+ + Cl^- -> AgCl(v)}}}
In a neutralization or acid/base reaction, the net ionic equation will usually be:
H
+
(
aq
)
+
OH
−
(
aq
)
⟶
H
2
O
(
l
)
{\displaystyle {\ce {H+ (aq) + OH^{-}(aq) -> H2O(l)}}}
There are a few acid/base reactions that produce a precipitate in addition to the water molecule shown above. An example is the reaction of barium hydroxide with phosphoric acid, which produces not only water but also the insoluble salt barium phosphate. In this reaction, there are no spectator ions, so the net ionic equation is the same as the full ionic equation.
3
Ba
(
OH
)
2
+
2
H
3
PO
4
⟶
6
H
2
O
+
Ba
3
(
PO
4
)
2
↓
{\displaystyle {\ce {3Ba(OH)2 + 2H3PO4 -> 6H2O + Ba3(PO4)2(v)}}}
3
Ba
2
+
+
6
OH
−
+
6
H
+
+
2
PO
4
3
−
⏟
phosphate
⟶
6
H
2
O
+
Ba
3
(
PO
4
)
2
↓
⏟
barium
phosphate
{\displaystyle {\ce {{3Ba^{2}+}+{6OH^{-}}+{6H+}}}+\underbrace {\ce {2PO4^{3}-}} _{\ce {phosphate}}{\ce {->{6H2O}+\underbrace {Ba3(PO4)2(v)} _{barium~phosphate}}}}
Double displacement reactions that feature a carbonate reacting with an acid have the net ionic equation:
2
H
+
+
CO
3
2
−
⏟
carbonate
⟶
H
2
O
+
CO
2
↑
{\displaystyle {\ce {2H+}}+\underbrace {{\ce {CO3^2-}}} _{{\ce {carbonate}}}{\ce {-> H2O + CO2 (^)}}}
If every ion is a "spectator ion" then there was no reaction, and the net ionic equation is null.
Generally, if zj is the multiple of elementary charge on the j-th molecule, charge neutrality may be written as:
∑
j
=
1
J
z
j
ν
j
=
0
{\displaystyle \sum _{j=1}^{J}z_{j}\nu _{j}=0}
where the νj are the stoichiometric coefficients described above. The zj may be incorporated
as an additional row in the aij matrix described above, and a properly balanced ionic equation will then also obey:
∑
j
=
1
J
a
i
j
ν
j
=
0
{\displaystyle \sum _{j=1}^{J}a_{ij}\nu _{j}=0}
== History ==
== Typesetting ==
== See also ==
Mathematical notation
Comparison of TeX editors
TeX extentions for science and chemistry notation
Chemistry notation in TeX
== Notes ==
== References == | Wikipedia/Ionic_equation |
An acidity function is a measure of the acidity of a medium or solvent system, usually expressed in terms of its ability to donate protons to (or accept protons from) a solute (Brønsted acidity). The pH scale is by far the most commonly used acidity function, and is ideal for dilute aqueous solutions. Other acidity functions have been proposed for different environments, most notably the Hammett acidity function, H0, for superacid media and its modified version H− for superbasic media. The term acidity function is also used for measurements made on basic systems, and the term basicity function is uncommon.
Hammett-type acidity functions are defined in terms of a buffered medium containing a weak base B and its conjugate acid BH+:
H
0
=
p
K
a
+
log
c
B
c
B
H
+
{\displaystyle H_{0}={\rm {p}}K_{\rm {a}}+\log {{c_{\rm {B}}} \over {c_{\rm {BH^{+}}}}}}
where pKa is the dissociation constant of BH+. They were originally measured by using nitroanilines as weak bases or acid-base indicators and by measuring the concentrations of the protonated and unprotonated forms with UV-visible spectroscopy. Other spectroscopic methods, such as NMR, may also be used. The function H− is defined similarly for strong bases:
H
−
=
p
K
a
+
log
c
B
−
c
B
H
{\displaystyle H_{-}={\rm {p}}K_{\rm {a}}+\log {{c_{\rm {B^{-}}}} \over {c_{\rm {BH}}}}}
Here BH is a weak acid used as an acid-base indicator, and B− is its conjugate base.
== Comparison of acidity functions with aqueous acidity ==
In dilute aqueous solution, the predominant acid species is the hydrated hydrogen ion H3O+ (or more accurately [H(OH2)n]+). In this case H0 and H− are equivalent to pH values determined by the buffer equation or Henderson-Hasselbalch equation.
However, an H0 value of −21 (a 25% solution of SbF5 in HSO3F) does not imply a hydrogen ion concentration of 1021 mol/dm3: such a "solution" would have a density more than a hundred times greater than a neutron star. Rather, H0 = −21 implies that the reactivity (protonating power) of the solvated hydrogen ions is 1021 times greater than the reactivity of the hydrated hydrogen ions in an aqueous solution of pH 0. The actual reactive species are different in the two cases, but both can be considered to be sources of H+, i.e. Brønsted acids. The hydrogen ion H+ never exists on its own in a condensed phase, as it is always solvated to a certain extent. The high negative value of H0 in SbF5/HSO3F mixtures indicates that the solvation of the hydrogen ion is much weaker in this solvent system than in water. Other way of expressing the same phenomenon is to say that SbF5·FSO3H is a much stronger proton donor than H3O+.
== References == | Wikipedia/Acidity_function |
Association theory (also aggregate theory) is a theory first advanced by chemist Thomas Graham in 1861 to describe the molecular structure of colloidal substances such as cellulose and starch, now understood to be polymers. Association theory postulates that such materials are solely composed of a collection of smaller molecules bound together by an unknown force. Graham termed these materials colloids. Prior to the development of macromolecular theory by Hermann Staudinger in the 1920s, which stated that individual polymers are composed of chains of covalently bonded monomers, association theory remained the most prevalent model of polymer structure in the scientific community.
Importantly, although polymers consist of long chains of covalently linked molecules, the individual polymer chains can often still associate and undergo phase transitions and phase separation to form colloids, liquid crystals, solid crystals, or aggregates. For biopolymers, association leads to formation of biomolecular condensates, micelles and other examples of molecular self-assembly.
== Bibliography ==
Morawetz, Herbert Polymers: The Origins and Growth of a Science John Wiley and Sons, 1985.
Utracki, L. A. Commercial Polymer Blends London: Chapman and Hall, 1998.
https://books.google.com/books?id=aLrrCAAAQBAJ&pg=PA14 | Wikipedia/Association_theory |
A coating is a covering that is applied to the surface of an object, or substrate. The purpose of applying the coating may be decorative, functional, or both. Coatings may be applied as liquids, gases or solids e.g. powder coatings.
Paints and lacquers are coatings that mostly have dual uses, which are protecting the substrate and being decorative, although some artists paints are only for decoration, and the paint on large industrial pipes is for identification (e.g. blue for process water, red for fire-fighting control) in addition to preventing corrosion. Along with corrosion resistance, functional coatings may also be applied to change the surface properties of the substrate, such as adhesion, wettability, or wear resistance. In other cases the coating adds a completely new property, such as a magnetic response or electrical conductivity (as in semiconductor device fabrication, where the substrate is a wafer), and forms an essential part of the finished product.
A major consideration for most coating processes is controlling coating thickness. Methods of achieving this range from a simple brush to expensive precision machinery in the electronics industry. Limiting coating area is crucial in some applications, such as printing.
"Roll-to-roll" or "web-based" coating is the process of applying a thin film of functional material to a substrate on a roll, such as paper, fabric, film, foil, or sheet stock. This continuous process is highly efficient for producing large volumes of coated materials, which are essential in various industries including printing, packaging, and electronics. The technology allows for consistent high-quality application of the coating material over large surface areas, enhancing productivity and uniformity.
== Applications ==
Coatings can be both decorative and have other functions. A pipe carrying water for a fire suppression system can be coated with a red (for identification) anticorrosion paint. Most coatings to some extent protect the substrate, such as maintenance coatings for metals and concrete. A decorative coating can offer a particular reflective property, such as high gloss, satin, matte, or flat appearance.
A major coating application is to protect metal from corrosion. Automotive coatings are used to enhance the appearance and durability of vehicles. These include primers, basecoats, and clearcoats, primarily applied with spray guns and electrostatically.
The body and underbody of automobiles receive some form of underbody coating. Such anticorrosion coatings may use graphene in combination with water-based epoxies.
Coatings are used to seal the surface of concrete, such as seamless polymer/resin flooring, bund wall/containment lining, waterproofing and damp proofing concrete walls, and bridge decks. Compare with tradition coatings, moisture curing polyurethane has been widely used because of the excellent adaptability and ease of construction. The mechanical properties could be enhanced by introducing multiple hydrogen bonds and optimize the microphase separation structure.
Most roof coatings are designed primarily for waterproofing, though sun reflection (to reduce heating and cooling) may also be a consideration. They tend to be elastomeric to allow for movement of the roof without cracking within the coating membrane.
Wood has been a key material in construction since ancient times, so its preservation by coating has received much attention. Efforts to improve the performance of wood coatings continue.
Coatings are used to alter tribological properties and wear characteristics. These include anti-friction, wear and scuffing resistance coatings for rolling-element bearings
=== Other ===
Other functions of coatings include:
Anti-fouling coatings
Anti-microbial coatings.
Anti-reflective coatings for example on spectacles.
Coatings that alter or have magnetic, electrical or electronic properties.
Flame retardant coatings. Flame-retardant materials and coatings are being developed that are phosphorus and bio-based. These include coatings with intumescent functionality.
Non-stick PTFE coated cooking pots/pans.
Optical coatings are available that alter optical properties of a material or object.
UV coatings
== Analysis and characterization ==
Numerous destructive and non-destructive evaluation (NDE) methods exist for characterizing coatings. The most common destructive method is microscopy of a mounted cross-section of the coating and its substrate. The most common non-destructive techniques include ultrasonic thickness measurement, X-ray fluorescence (XRF), X-Ray diffraction (XRD), photothermal coating thickness measurement and micro hardness indentation. X-ray photoelectron spectroscopy (XPS) is also a classical characterization method to investigate the chemical composition of the nanometer thick surface layer of a material. Scanning electron microscopy coupled with energy dispersive X-ray spectrometry (SEM-EDX, or SEM-EDS) allows to visualize the surface texture and to probe its elementary chemical composition. Other characterization methods include transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning tunneling microscope (STM), and Rutherford backscattering spectrometry (RBS). Various methods of Chromatography are also used, as well as thermogravimetric analysis.
== Formulation ==
The formulation of a coating depends primarily on the function required of the coating and also on aesthetics required such as color and gloss. The four primary ingredients are the resin (or binder), solvent which may be water (or solventless), pigment(s) and additives. Research is ongoing to remove heavy metals from coating formulations completely.
For example, on the basis of experimental and epidemiological evidence, it has been classified by the IARC (International Agency for Research on Cancer) as a human carcinogen by inhalation (class I) (ISPESL, 2008).
== Processes ==
Coating processes may be classified as follows:
=== Vapor deposition ===
==== Chemical vapor deposition ====
Metalorganic vapour phase epitaxy
Electrostatic spray assisted vapour deposition (ESAVD)
Sherardizing
Some forms of Epitaxy
Molecular beam epitaxy
==== Physical vapor deposition ====
Cathodic arc deposition
Electron beam physical vapor deposition (EBPVD)
Ion plating
Ion beam assisted deposition (IBAD)
Magnetron sputtering
Pulsed laser deposition
Sputter deposition
Vacuum deposition
Vacuum evaporation, evaporation (deposition)
Pulsed electron deposition (PED)
=== Chemical and electrochemical techniques ===
Conversion coating
Autophoretic, the registered trade name of a proprietary series of auto-depositing coatings specifically for ferrous metal substrates
Anodising
Chromate conversion coating
Plasma electrolytic oxidation
Phosphate (coating)
Ion beam mixing
Pickled and oiled, a type of plate steel coating
Plating
Electroless plating
nickel plating coating using a different material to preserve mechanical properties
Electroplating
=== Spraying ===
Spray painting
High velocity oxygen fuel (HVOF)
Plasma spraying
Thermal spraying
Kinetic metallization (KM)
Plasma transferred wire arc thermal spraying
The common forms of Powder coating
=== Roll-to-roll coating processes ===
Common roll-to-roll coating processes include:
Air knife coating
Anilox coater
Flexo coater
Gap Coating
Knife-over-roll coating
Gravure coating
Hot melt coating- when the necessary coating viscosity is achieved by temperature rather than solution of the polymers etc. This method commonly implies slot-die coating above room temperature, but it also is possible to have hot-melt roller coating; hot-melt metering-rod coating, etc.
Immersion dip coating
Kiss coating
Metering rod (Meyer bar) coating
Roller coating
Forward roller coating
Reverse roll coating
Silk Screen coater
Rotary screen
Slot Die coating - Slot die coating was originally developed in the 1950s. Slot die coating has a low operational cost and is an easily scaled processing technique for depositing thin and uniform films rapidly, while minimizing material waste. Slot die coating technology is used to deposit a variety of liquid chemistries onto substrates of various materials such as glass, metal, and polymers by precisely metering the process fluid and dispensing it at a controlled rate while the coating die is precisely moved relative to the substrate. The complex inner geometry of conventional slot dies require machining or can be accomplished with 3-D printing.
Extrusion coating - generally high pressure, often high temperature, and with the web travelling much faster than the speed of the extruded polymer
Curtain coating- low viscosity, with the slot vertically above the web and a gap between slot-die and web.
Slide coating- bead coating with an angled slide between the slot-die and the bead. Commonly used for multilayer coating in the photographic industry.
Slot die bead coating- typically with the web backed by a roller and a very small gap between slot-die and web.
Tensioned-web slot-die coating- with no backing for the web.
Inkjet printing
Lithography
Flexography
=== Physical ===
Langmuir-Blodgett
Spin coating
Dip coating
== See also ==
== References ==
== Further reading ==
Müller, Bodo (2006). Coatings formulation : an international textbook. Urlich Poth. Hannover: Vincentz. ISBN 3-87870-177-2. OCLC 76886114.
Spyrou, Emmanouil (2012). Powder coatings chemistry and technology (3 ed.). Vincentz Network. ISBN 978-3-86630-884-8. OCLC 828194496.
Titanium and titanium alloys, edited by C. Leyens and M. Peters, Wiley-VCH, ISBN 3-527-30534-3, table 6.2: overview of several coating systems and fabriction processes for titanium alloys and titanium aluminides (amended)
Coating Materials for Electronic Applications: Polymers, Processes, Reliability, Testing by James J. Licari; William Andrew Publishing, Elsevier, ISBN 0-8155-1492-1
High-Performance Organic Coatings, ed. AS Khanna, Elsevier BV, 2015, ISBN 978-1-84569-265-0 | Wikipedia/Industrial_coating |
The Mark–Houwink equation, also known as the Mark–Houwink–Sakurada equation or the Kuhn–Mark–Houwink–Sakurada equation or the Landau–Kuhn–Mark–Houwink–Sakurada equation or the Mark-Chrystian equation gives a relation between intrinsic viscosity
[
η
]
{\displaystyle [\eta ]}
and molecular weight
M
{\displaystyle M}
:
[
η
]
=
K
M
a
{\displaystyle [\eta ]=KM^{a}}
From this equation the molecular weight of a polymer can be determined from data on the intrinsic viscosity and vice versa.
The values of the Mark–Houwink parameters,
a
{\displaystyle a}
and
K
{\displaystyle K}
, depend on the particular polymer-solvent system as well as temperature. For solvents, a value of
a
=
0.5
{\displaystyle a=0.5}
is indicative of a theta solvent. A value of
a
=
0.8
{\displaystyle a=0.8}
is typical for good solvents. For most flexible polymers,
0.5
≤
a
≤
0.8
{\displaystyle 0.5\leq a\leq 0.8}
. For semi-flexible polymers,
a
≥
0.8
{\displaystyle a\geq 0.8}
. For polymers with an absolute rigid rod, such as Tobacco mosaic virus,
a
=
2.0
{\displaystyle a=2.0}
.
It is named after Herman F. Mark and Roelof Houwink.
== Applications ==
The Mark-Houwink equation is used in size-exclusion chromatography (SEC) to construct the so called universal calibration curve which can be used to determine the molecular weight of a polymer A using a calibration done with polymer B.
In SEC molecules are separated based on hydrodynamic volume, i.e. the size of the coil a given polymer forms in solution. The hydrodynamic volume, however, cannot simply be related to molecular weight (compare comb-like polystyrene vs. linear polystyrene). This means that the molecular weight associated with a given retention volume is substance specific and that in order to determine the molecular weight of a given polymer a molecular-weight size marker of the same substance must be available.
However, the product of the intrinsic viscosity and the molecular weight,
[
η
]
M
{\displaystyle [\eta ]M}
, is proportional to the hydrodynamic radius and therefore independent of substance. It follows that
[
η
]
A
M
A
=
[
η
]
B
M
B
{\displaystyle [\eta ]_{A}M_{A}=[\eta ]_{B}M_{B}}
is true at any given retention volume. Substitution of
[
η
]
{\displaystyle [\eta ]}
using the Mark-Houwink equation gives:
K
A
M
A
a
A
+
1
=
K
B
M
B
a
B
+
1
{\displaystyle K_{A}M_{A}^{a_{A}+1}=K_{B}M_{B}^{a_{B}+1}}
which can be used to relate the molecular weight of any two polymers using their Mark-Houwink constants (i.e. "universally" applicable for calibration).
For example, if narrow molar mass distribution standards are available for polystyrene, these can be used to construct a calibration curve (typically
l
o
g
M
{\displaystyle logM}
vs. retention volume ) in eg. toluene at 40 °C. This calibration can then be used to determine the "polystyrene equivalent" molecular weight of a polyethylene sample if the Mark-Houwink parameters for both substances are known in this solvent at this temperature.
== References == | Wikipedia/Mark–Houwink_equation |
Gel permeation chromatography (GPC) is a type of size-exclusion chromatography (SEC), that separates high molecular weight or colloidal analytes on the basis of size or diameter, typically in organic solvents. The technique is often used for the analysis of polymers. As a technique, SEC was first developed in 1955 by Lathe and Ruthven. The term gel permeation chromatography can be traced back to J.C. Moore of the Dow Chemical Company who investigated the technique in 1964. The proprietary column technology was licensed to Waters Corporation, who subsequently commercialized this technology in 1964. GPC systems and consumables are now also available from a number of manufacturers. It is often necessary to separate polymers, both to analyze them as well as to purify the desired product.
When characterizing polymers, it is important to consider their size distribution and dispersity (Đ) as well their molecular weight. Polymers can be characterized by a variety of definitions for molecular weight including the number average molecular weight (Mn), the weight average molecular weight (Mw) (see molar mass distribution), the size average molecular weight (Mz), or the viscosity molecular weight (Mv). GPC allows for the determination of Đ as well as Mv and, based on other data, the Mn, Mw, and Mz can be determined.
== How it works ==
GPC is a type of chromatography in which analytes are separated, based on their size or hydrodynamic volume (radius of gyration). This differs from other chromatographic techniques, which depend upon chemical or physical interactions between the mobile and stationary phases to separate analytes. Separation occurs via the use of porous gel beads packed inside a column (see stationary phase (chemistry)). The principle of separation relies on the differential exclusion or inclusion of the macromolecules by the porous gel stationary phase. Larger molecules are excluded from entering the pores and elute earlier, while smaller molecules can enter the pores, thus staying longer inside the column. The entire process takes place without any interaction of the analytes with the surface of the stationary phase. The smaller analytes relative to the pore sizes can permeate these pores and spend more time inside the gel particles, increasing their retention time. Conversely, larger analytes relative to the pores sizes spend little if any time inside the column, hence they elute sooner. Each type of column has a range of molecular weights that can be separated, according to their pores sizes. If an analyte is too large relative to the column's pores, it will not be retained at all and will be totally excluded; conversely, if the analyte is small relative to the pores sizes, it will be totally permeating. Analytes that are totally excluded, elute with the free volume outside around the particles (Vo), the total exclusion limit, while analytes that are completely delayed, elute with the solvent, marking the total permeation volume of the column, including also the solvent held inside the pores (Vi). The total volume can be considered by the following equation, where Vg is the volume of the polymer gel and Vt is the total volume:
V
t
=
V
g
+
V
i
+
V
o
{\displaystyle Vt=Vg+Vi+Vo}
As can be inferred, there is a limited range of molecular weights that can be separated by each column, therefore the size of the pores for the packing should be chosen according to the range of molecular weight of analytes to be separated. For polymer separations the pore sizes should be on the order of the polymers being analyzed. If a sample has a broad molecular weight range it may be necessary to use several GPC columns with varying pores volumes in tandem to resolve the sample fully.
== Application ==
GPC is often used to determine the relative molecular weight of polymer samples as well as the distribution of molecular weights. What GPC truly measures is the molecular volume and shape function as defined by the intrinsic viscosity. If comparable standards are used, this relative data can be used to determine molecular weights within ± 5% accuracy. Polystyrene standards with dispersities of less than 1.2 are typically used to calibrate the GPC. Unfortunately, polystyrene tends to be a very linear polymer and therefore as a standard it is only useful to compare it to other polymers that are known to be linear and of relatively the same size.
== Material and methods ==
=== Instrumentation ===
Gel permeation chromatography is conducted almost exclusively in chromatography systems. The experimental design is not much different from other techniques of High Performance liquid chromatography. Samples are dissolved in an appropriate solvent, in the case of GPC these tend to be organic solvents and after filtering the solution it is injected onto a column. The separation of multi-component mixture takes place in the column. The constant supply of fresh eluent to the column is accomplished by the use of a pump. Since most analytes are not visible to the naked eye a detector is needed. Often multiple detectors are used to gain additional information about the polymer sample. The availability of a detector makes the fractionation convenient and accurate.
=== Gel ===
Gels are used as stationary phase for GPC. The pore size of a gel must be carefully controlled in order to be able to apply the gel to a given separation. Other desirable properties of the gel forming agent are the absence of ionizing groups and, in a given solvent, low affinity for the substances to be separated. Commercial gels like PLgel & Styragel (cross-linked polystyrene-divinylbenzene), LH-20 (hydroxypropylated Sephadex), Bio-Gel (cross-linked polyacrylamide), HW-20 & HW-40 (hydroxylated methacrylic polymer), and agarose gel are often used based on different separation requirements.
=== Column ===
The column used for GPC is filled with a microporous packing material. The column is filled with the gel. Since the total penetration volume is the maximum volume permeated by the analytes, and there is no retention on the surface of the stationary phase, the total column volume is usually large, relatively to the sample volume.
=== Eluent ===
The eluent (mobile phase) should be the appropriate solvent to dissolve the polymer, should not interfere with the response of the polymer analyzed, and should wet the packing surface and make it inert to interactions with the polymers. The most common eluents for polymers that dissolve at room temperature GPC are tetrahydrofuran (THF), o-dichlorobenzene and trichlorobenzene at 130–150 °C for crystalline polyalkynes and hexafluoroisopropanol (HFIP) for crystalline condensation polymers such as polyamides and polyesters.
=== Pump ===
There are two types of pumps available for uniform delivery of relatively small liquid volumes for GPC: piston or peristaltic pumps. The delivery of a constant flow free of fluctuations is especially important to the precision of the GPC analysis, as the flow-rate is used for the calibration of the molecular weight, or diameter.
=== Detector ===
In GPC, the concentration by weight of polymer in the eluting solvent may be monitored continuously with a detector. There are many detector types available and they can be divided into two main categories. The first is concentration sensitive detectors which includes UV-VIS absorption, differential refractometer (DRI) or refractive index (RI) detectors, infrared (IR) absorption and density detectors. The second category is molecular weight sensitive detectors, which include low angle light scattering detectors (LALLS) and multi angle light scattering (MALS). The resulting chromatogram is therefore a weight distribution of the polymer as a function of retention volume. The most sensitive detector is the differential UV photometer and the most common detector is the differential refractometer (DRI). When characterizing copolymer, it is necessary to have two detectors in series. For accurate determinations of copolymer composition at least two of those detectors should be concentration detectors. The determination of most copolymer compositions is done using UV and RI detectors, although other combinations can be used.
== Data analysis ==
Gel permeation chromatography (GPC) has become the most widely used technique for analyzing polymer samples in order to determine their molecular weights and weight distributions. Examples of GPC chromatograms of polystyrene samples with their molecular weights and dispersities are shown on the left.
Benoit and co-workers proposed that the hydrodynamic volume, Vη, which is proportional to the product of [η] and M, where [η] is the intrinsic viscosity of the polymer in the SEC eluent, may be used as the universal calibration parameter. If the Mark–Houwink–Sakurada constants K and α are known (see Mark–Houwink equation), a plot of log [η]M versus elution volume (or elution time) for a particular solvent, column and instrument provides a universal calibration curve which can be used for any polymer in that solvent. By determining the retention volumes (or times) of monodisperse polymer standards (e.g. solutions of monodispersed polystyrene in THF), a calibration curve can be obtained by plotting the logarithm of the molecular weight versus the retention time or volume. Once the calibration curve is obtained, the gel permeation chromatogram of any other polymer can be obtained in the same solvent and the molecular weights (usually Mn and Mw) and the complete molecular weight distribution for the polymer can be determined. A typical calibration curve is shown to the right and the molecular weight from an unknown sample can be obtained from the calibration curve.
== Advantages ==
As a separation technique, GPC has many advantages. First of all, it has a well-defined separation time due to the fact that there is a final elution volume for all unretained analytes. Additionally, GPC can provide narrow bands, although this aspect of GPC is more difficult for polymer samples that have broad ranges of molecular weights present. Finally, since the analytes do not interact chemically or physically with the column, there is a lower chance for analyte loss to occur. For investigating the properties of polymer samples in particular, GPC can be very advantageous. GPC provides a more convenient method of determining the molecular weights of polymers. In fact most samples can be thoroughly analyzed in an hour or less. Other methods used in the past were fractional extraction and fractional precipitation. As these processes were quite labor-intensive molecular weights and mass distributions typically were not analyzed. Therefore, GPC has allowed for the quick and relatively easy estimation of molecular weights and distribution for polymer samples
== Disadvantages ==
There are disadvantages to GPC, however. First, there is a limited number of peaks that can be resolved within the short time scale of the GPC run. Also, as a technique GPC requires around at least a 10% difference in molecular weight for a reasonable resolution of peaks to occur. In regards to polymers, the molecular masses of most of the chains will be too close for the GPC separation to show anything more than broad peaks. Another disadvantage of GPC for polymers is that filtrations must be performed before using the instrument to prevent dust and other particulates from ruining the columns and interfering with the detectors. Although useful for protecting the instrument, there is the possibility of the pre-filtration of the sample removing higher molecular weight sample before it can be loaded on the column. Another possibility to overcome these issues is the separation by field-flow fractionation (FFF).
== Orthogonal methods ==
Field-flow fractionation (FFF) can be considered as an alternative to GPC, especially when particles or high molar mass polymers cause clogging of the column, shear degradation is an issue or agglomeration takes place but cannot be made visible. FFF is separation in an open flow channel without having a static phase involved so no interactions occur. With one field-flow fractionation version, thermal field-flow fractionation, separation of polymers having the same size but different chemical compositions is possible.
== References == | Wikipedia/Gel_permeation_chromatography |
The Hammett acidity function (H0) is a measure of acidity that is used for very concentrated solutions of strong acids, including superacids. It was proposed by the physical organic chemist Louis Plack Hammett and is the best-known acidity function used to extend the measure of Brønsted–Lowry acidity beyond the dilute aqueous solutions for which the pH scale is useful.
In highly concentrated solutions, simple approximations such as the Henderson–Hasselbalch equation are no longer valid due to the variations of the activity coefficients. The Hammett acidity function is used in fields such as physical organic chemistry for the study of acid-catalyzed reactions, because some of these reactions use acids in very high concentrations, or even neat (pure).
== Definition ==
The Hammett acidity function, H0, can replace the pH in concentrated solutions. It is defined using an equation analogous to the Henderson–Hasselbalch equation:
H
0
=
p
K
BH
+
+
log
[
B
]
[
BH
+
]
{\displaystyle H_{0}={\mbox{p}}K_{{\ce {BH^+}}}+\log {\frac {{\ce {[B]}}}{{\ce {[BH^+]}}}}}
where log(x) is the common logarithm of x, and pKBH+ is −log(K) for the dissociation of BH+, which is the conjugate acid of a very weak base B, with a very negative pKBH+. In this way, it is rather as if the pH scale has been extended to very negative values. Hammett originally used a series of anilines with electron-withdrawing groups for the bases.
Hammett also pointed out the equivalent form
H
0
=
−
log
(
a
H
+
γ
B
γ
BH
+
)
{\displaystyle H_{0}=-\log \left(a_{{\ce {H^+}}}{\frac {\gamma _{{\ce {B}}}}{\gamma _{{\ce {BH^+}}}}}\right)}
where a is the activity, and the γ are thermodynamic activity coefficients. In dilute aqueous solution (pH 0–14) the predominant acid species is H3O+ and the activity coefficients are close to unity, so H0 is approximately equal to the pH. However, beyond this pH range, the effective hydrogen-ion activity changes much more rapidly than the concentration. This is often due to changes in the nature of the acid species; for example in concentrated sulfuric acid, the predominant acid species ("H+") is not H3O+ but rather H3SO4+, which is a much stronger acid. The value H0 = −12 for pure sulfuric acid must not be interpreted as pH = −12 (which would imply an impossibly high H3O+ concentration of 10+12 mol/L in ideal solution). Instead it means that the acid species present (H3SO4+) has a protonating ability equivalent to H3O+ at a fictitious (ideal) concentration of 1012 mol/L, as measured by its ability to protonate weak bases.
Although the Hammett acidity function is the best known acidity function, other acidity functions have been developed by authors such as Arnett, Cox, Katrizky, Yates, and Stevens.
== Typical values ==
On this scale, pure H2SO4 (18.4 M) has a H0 value of −12, and pyrosulfuric acid has H0 ~ −15. Take note that the Hammett acidity function clearly avoids water in its equation. It is a generalization of the pH scale—in a dilute aqueous solution (where B is H2O), pH is very nearly equal to H0. By using a solvent-independent quantitative measure of acidity, the implications of the leveling effect are eliminated, and it becomes possible to directly compare the acidities of different substances (e.g. using pKa, HF is weaker than HCl or H2SO4 in water but stronger than HCl in glacial acetic acid.)
For mixtures (e.g., partly diluted acids in water), the acidity function depends on the composition of the mixture and has to be determined empirically. Graphs of H0 vs mole fraction can be found in the literature for many acids.
== References == | Wikipedia/Hammett_acidity_function |
In chemistry, an acid–base reaction is a chemical reaction that occurs between an acid and a base. It can be used to determine pH via titration. Several theoretical frameworks provide alternative conceptions of the reaction mechanisms and their application in solving related problems; these are called the acid–base theories, for example, Brønsted–Lowry acid–base theory.
Their importance becomes apparent in analyzing acid–base reactions for gaseous or liquid species, or when acid or base character may be somewhat less apparent. The first of these concepts was provided by the French chemist Antoine Lavoisier, around 1776.
It is important to think of the acid–base reaction models as theories that complement each other. For example, the current Lewis model has the broadest definition of what an acid and base are, with the Brønsted–Lowry theory being a subset of what acids and bases are, and the Arrhenius theory being the most restrictive.
== Acid–base definitions ==
=== Historic development ===
The concept of an acid–base reaction was first proposed in 1754 by Guillaume-François Rouelle, who introduced the word "base" into chemistry to mean a substance which reacts with an acid to give it solid form (as a salt). Bases are mostly bitter in nature.
==== Lavoisier's oxygen theory of acids ====
The first scientific concept of acids and bases was provided by Lavoisier in around 1776. Since Lavoisier's knowledge of strong acids was mainly restricted to oxoacids, such as HNO3 (nitric acid) and H2SO4 (sulfuric acid), which tend to contain central atoms in high oxidation states surrounded by oxygen, and since he was not aware of the true composition of the hydrohalic acids (HF, HCl, HBr, and HI), he defined acids in terms of their containing oxygen, which in fact he named from Greek words meaning "acid-former" (from Greek ὀξύς (oxys) 'acid, sharp' and γεινομαι (geinomai) 'engender'). The Lavoisier definition held for over 30 years, until the 1810 article and subsequent lectures by Sir Humphry Davy in which he proved the lack of oxygen in hydrogen sulfide (H2S), hydrogen telluride (H2Te), and the hydrohalic acids. However, Davy failed to develop a new theory, concluding that "acidity does not depend upon any particular elementary substance, but upon peculiar arrangement of various substances". One notable modification of oxygen theory was provided by Jöns Jacob Berzelius, who stated that acids are oxides of nonmetals while bases are oxides of metals.
==== Liebig's hydrogen theory of acids ====
In 1838, Justus von Liebig proposed that an acid is a hydrogen-containing compound whose hydrogen can be replaced by a metal. This redefinition was based on his extensive work on the chemical composition of organic acids, finishing the doctrinal shift from oxygen-based acids to hydrogen-based acids started by Davy. Liebig's definition, while completely empirical, remained in use for almost 50 years until the adoption of the Arrhenius definition.
=== Arrhenius definition ===
The first modern definition of acids and bases in molecular terms was devised by Svante Arrhenius. A hydrogen theory of acids, it followed from his 1884 work with Friedrich Wilhelm Ostwald in establishing the presence of ions in aqueous solution and led to Arrhenius receiving the Nobel Prize in Chemistry in 1903.
As defined by Arrhenius:
An Arrhenius acid is a substance that ionises in water to form hydrogen cations (H+); that is, an acid increases the concentration of H+ ions in an aqueous solution.
This causes the protonation of water, or the creation of the hydronium (H3O+) ion. Thus, in modern times, the symbol H+ is interpreted as a shorthand for H3O+, because it is now known that a bare proton does not exist as a free species in aqueous solution. This is the species which is measured by pH indicators to measure the acidity or basicity of a solution.
An Arrhenius base is a substance that dissociates in water to form hydroxide (OH−) ions; that is, a base increases the concentration of OH− ions in an aqueous solution.
The Arrhenius definitions of acidity and alkalinity are restricted to aqueous solutions and are not valid for most non-aqueous solutions, and refer to the concentration of the solvent ions. Under this definition, pure H2SO4 and HCl dissolved in toluene are not acidic, and molten NaOH and solutions of calcium amide in liquid ammonia are not alkaline. This led to the development of the Brønsted–Lowry theory and subsequent Lewis theory to account for these non-aqueous exceptions.
The reaction of an acid with a base is called a neutralization reaction. The products of this reaction are a salt and water.
acid
+
base
⟶
salt
+
water
{\displaystyle {\text{acid}}\ +\ {\text{base}}\ \longrightarrow \ {\text{salt}}\ +\ {\text{water}}}
In this traditional representation an acid–base neutralization reaction is formulated as a double-replacement reaction. For example, the reaction of hydrochloric acid (HCl) with sodium hydroxide (NaOH) solutions produces a solution of sodium chloride (NaCl) and some additional water molecules.
HCl
(
aq
)
+
NaOH
(
aq
)
⟶
NaCl
(
aq
)
+
H
2
O
{\displaystyle {\ce {HCl_{(aq)}{}+ NaOH_{(aq)}-> NaCl_{(aq)}{}+ H2O}}}
The modifier (aq) in this equation was implied by Arrhenius, rather than included explicitly. It indicates that the substances are dissolved in water. Though all three substances, HCl, NaOH and NaCl are capable of existing as pure compounds, in aqueous solutions they are fully dissociated into the aquated ions H+, Cl−, Na+ and OH−.
==== Example: Baking powder ====
Baking powder is used to cause the dough for breads and cakes to "rise" by creating millions of tiny carbon dioxide bubbles. Baking powder is not to be confused with baking soda, which is sodium bicarbonate (NaHCO3). Baking powder is a mixture of baking soda (sodium bicarbonate) and acidic salts. The bubbles are created because, when the baking powder is combined with water, the sodium bicarbonate and acid salts react to produce gaseous carbon dioxide.
Whether commercially or domestically prepared, the principles behind baking powder formulations remain the same. The acid–base reaction can be generically represented as shown:
NaHCO
3
+
H
+
⟶
Na
+
+
CO
2
+
H
2
O
{\displaystyle {\ce {NaHCO3 + H+ -> Na+ + CO2 + H2O}}}
The real reactions are more complicated because the acids are complicated. For example, starting with sodium bicarbonate and monocalcium phosphate (Ca(H2PO4)2), the reaction produces carbon dioxide by the following stoichiometry:
14
NaHCO
3
+
5
Ca
(
H
2
PO
4
)
2
⟶
14
CO
2
+
Ca
5
(
PO
4
)
3
OH
+
7
Na
2
HPO
4
+
13
H
2
O
{\displaystyle {\ce {14 NaHCO3 + 5 Ca(H2PO4)2 -> 14 CO2 + Ca5(PO4)3OH + 7 Na2HPO4 + 13 H2O}}}
A typical formulation (by weight) could call for 30% sodium bicarbonate, 5–12% monocalcium phosphate, and 21–26% sodium aluminium sulfate. Alternately, a commercial baking powder might use sodium acid pyrophosphate as one of the two acidic components instead of sodium aluminium sulfate. Another typical acid in such formulations is cream of tartar (KC4H5O6), a derivative of tartaric acid.
=== Brønsted–Lowry definition ===
The Brønsted–Lowry definition, formulated in 1923, independently by Johannes Nicolaus Brønsted in Denmark and Martin Lowry in England, is based upon the idea of protonation of bases through the deprotonation of acids – that is, the ability of acids to "donate" hydrogen cations (H+) – otherwise known as protons – to bases, which "accept" them.
An acid–base reaction is, thus, the removal of a proton from the acid and its addition to the base. The removal of a proton from an acid produces its conjugate base, which is the acid with a proton removed. The reception of a proton by a base produces its conjugate acid, which is the base with a proton added.
Unlike the previous definitions, the Brønsted–Lowry definition does not refer to the formation of salt and solvent, but instead to the formation of conjugate acids and conjugate bases, produced by the transfer of a proton from the acid to the base. In this approach, acids and bases are fundamentally different in behavior from salts, which are seen as electrolytes, subject to the theories of Debye, Onsager, and others. An acid and a base react not to produce a salt and a solvent, but to form a new acid and a new base. The concept of neutralization is thus absent. Brønsted–Lowry acid–base behavior is formally independent of any solvent, making it more all-encompassing than the Arrhenius model. The calculation of pH under the Arrhenius model depended on alkalis (bases) dissolving in water (aqueous solution). The Brønsted–Lowry model expanded what could be pH tested using insoluble and soluble solutions (gas, liquid, solid).
The general formula for acid–base reactions according to the Brønsted–Lowry definition is:
HA
+
B
⟶
BH
+
+
A
−
{\displaystyle {\ce {HA + B -> BH+ + A-}}}
where HA represents the acid, B represents the base, BH+ represents the conjugate acid of B, and A− represents the conjugate base of HA.
For example, a Brønsted–Lowry model for the dissociation of hydrochloric acid (HCl) in aqueous solution would be the following:
HCl
acid
+
H
2
O
base
↽
−
−
⇀
H
3
O
+
conjugate
acid
+
Cl
−
conjugate
base
{\displaystyle {\underset {\text{acid}}{{\ce {HCl_{\,}}}}}\ +\ {\underset {\text{base}}{{\ce {H2O}}}}\quad {\ce {<=>}}\quad {\underset {{\text{conjugate }} \atop {\text{acid }}}{{\ce {H3O+}}}}\ +{\underset {{\text{conjugate}} \atop {\text{base}}}{{\ce {Cl_{\,}-}}}}}
The removal of H+ from the HCl produces the chloride ion, Cl−, the conjugate base of the acid. The addition of H+ to the H2O (acting as a base) forms the hydronium ion, H3O+, the conjugate acid of the base.
Water is amphoteric – that is, it can act as both an acid and a base. The Brønsted–Lowry model explains this, showing the dissociation of water into low concentrations of hydronium and hydroxide ions:
H
2
O
+
H
2
O
↽
−
−
⇀
H
3
O
+
+
OH
−
{\displaystyle {\ce {H2O + H2O <=> H3O+ + OH-}}}
This equation is demonstrated in the image below:
Here, one molecule of water acts as an acid, donating an H+ and forming the conjugate base, OH−, and a second molecule of water acts as a base, accepting the H+ ion and forming the conjugate acid, H3O+.
As an example of water acting as an acid, consider an aqueous solution of pyridine, C5H5N.
C
5
H
5
N
+
H
2
O
↽
−
−
⇀
[
C
5
H
5
NH
]
+
+
OH
−
{\displaystyle {\ce {C5H5N + H2O <=> [C5H5NH]+ + OH-}}}
In this example, a water molecule is split into a hydrogen cation, which is donated to a pyridine molecule, and a hydroxide ion.
In the Brønsted–Lowry model, the solvent does not necessarily have to be water, as is required by the Arrhenius Acid–Base model. For example, consider what happens when acetic acid, CH3COOH, dissolves in liquid ammonia.
CH
3
COOH
+
NH
3
↽
−
−
⇀
NH
4
+
+
CH
3
COO
−
{\displaystyle {\ce {CH3COOH + NH3 <=> NH4+ + CH3COO-}}}
An H+ ion is removed from acetic acid, forming its conjugate base, the acetate ion, CH3COO−. The addition of an H+ ion to an ammonia molecule of the solvent creates its conjugate acid, the ammonium ion, NH+4.
The Brønsted–Lowry model calls hydrogen-containing substances (like HCl) acids. Thus, some substances, which many chemists considered to be acids, such as SO3 or BCl3, are excluded from this classification due to lack of hydrogen. Gilbert N. Lewis wrote in 1938, "To restrict the group of acids to those substances that contain hydrogen interferes as seriously with the systematic understanding of chemistry as would the restriction of the term oxidizing agent to substances containing oxygen." Furthermore, KOH and KNH2 are not considered Brønsted bases, but rather salts containing the bases OH− and NH−2.
=== Lewis definition ===
The hydrogen requirement of Arrhenius and Brønsted–Lowry was removed by the Lewis definition of acid–base reactions, devised by Gilbert N. Lewis in 1923, in the same year as Brønsted–Lowry, but it was not elaborated by him until 1938. Instead of defining acid–base reactions in terms of protons or other bonded substances, the Lewis definition defines a base (referred to as a Lewis base) to be a compound that can donate an electron pair, and an acid (a Lewis acid) to be a compound that can receive this electron pair.
For example, boron trifluoride, BF3 is a typical Lewis acid. It can accept a pair of electrons as it has a vacancy in its octet. The fluoride ion has a full octet and can donate a pair of electrons. Thus
BF
3
+
F
−
⟶
BF
4
−
{\displaystyle {\ce {BF3 + F- -> BF4-}}}
is a typical Lewis acid, Lewis base reaction. All compounds of group 13 elements with a formula AX3 can behave as Lewis acids. Similarly, compounds of group 15 elements with a formula DY3, such as amines, NR3, and phosphines, PR3, can behave as Lewis bases. Adducts between them have the formula X3A←DY3 with a dative covalent bond, shown symbolically as ←, between the atoms A (acceptor) and D (donor). Compounds of group 16 with a formula DX2 may also act as Lewis bases; in this way, a compound like an ether, R2O, or a thioether, R2S, can act as a Lewis base. The Lewis definition is not limited to these examples. For instance, carbon monoxide acts as a Lewis base when it forms an adduct with boron trifluoride, of formula F3B←CO.
Adducts involving metal ions are referred to as co-ordination compounds; each ligand donates a pair of electrons to the metal ion. The reaction
[
Ag
(
H
2
O
)
4
]
+
+
2
NH
3
⟶
[
Ag
(
NH
3
)
2
]
+
+
4
H
2
O
{\displaystyle {\ce {[Ag(H2O)4]+ + 2 NH3 -> [Ag(NH3)2]+ + 4 H2O}}}
can be seen as an acid–base reaction in which a stronger base (ammonia) replaces a weaker one (water).
The Lewis and Brønsted–Lowry definitions are consistent with each other since the reaction
H
+
+
OH
−
↽
−
−
⇀
H
2
O
{\displaystyle {\ce {H+ + OH- <=> H2O}}}
is an acid–base reaction in both theories.
=== Solvent system definition ===
One of the limitations of the Arrhenius definition is its reliance on water solutions. Edward Curtis Franklin studied the acid–base reactions in liquid ammonia in 1905 and pointed out the similarities to the water-based Arrhenius theory. Albert F.O. Germann, working with liquid phosgene, COCl2, formulated the solvent-based theory in 1925, thereby generalizing the Arrhenius definition to cover aprotic solvents.
Germann pointed out that in many solutions, there are ions in equilibrium with the neutral solvent molecules:
solvonium ions: a generic name for positive ions. These are also sometimes called solvo-acids; when protonated solvent, they are lyonium ions.
solvate ions: a generic name for negative ions. These are also sometimes called solve-bases; when deprotonated solvent, they are lyate ions.
For example, water and ammonia undergo such dissociation into hydronium and hydroxide, and ammonium and amide, respectively:
H3O+ + OH-}}\\[4pt]{\ce {2 NH3}}&{\ce {\, <=> NH4+ + NH2-}}\end{aligned}}}">
2
H
2
O
↽
−
−
⇀
H
3
O
+
+
OH
−
2
NH
3
↽
−
−
⇀
NH
4
+
+
NH
2
−
{\displaystyle {\begin{aligned}{\ce {2 H2O}}&{\ce {\, <=> H3O+ + OH-}}\\[4pt]{\ce {2 NH3}}&{\ce {\, <=> NH4+ + NH2-}}\end{aligned}}}
Some aprotic systems also undergo such dissociation, such as dinitrogen tetroxide into nitrosonium and nitrate, antimony trichloride into dichloroantimonium and tetrachloroantimonate, and phosgene into chlorocarboxonium and chloride:
NO+ + NO3-}}\\[4pt]{\ce {2 SbCl3}}&{\ce {\, <=> SbCl2+ + SbCl4-}}\\[4pt]{\ce {COCl2}}&{\ce {\, <=> COCl+ + Cl-}}\end{aligned}}}">
N
2
O
4
↽
−
−
⇀
NO
+
+
NO
3
−
2
SbCl
3
↽
−
−
⇀
SbCl
2
+
+
SbCl
4
−
COCl
2
↽
−
−
⇀
COCl
+
+
Cl
−
{\displaystyle {\begin{aligned}{\ce {N2O4}}&{\ce {\, <=> NO+ + NO3-}}\\[4pt]{\ce {2 SbCl3}}&{\ce {\, <=> SbCl2+ + SbCl4-}}\\[4pt]{\ce {COCl2}}&{\ce {\, <=> COCl+ + Cl-}}\end{aligned}}}
A solute that causes an increase in the concentration of the solvonium ions and a decrease in the concentration of solvate ions is defined as an acid. A solute that causes an increase in the concentration of the solvate ions and a decrease in the concentration of the solvonium ions is defined as a base.
Thus, in liquid ammonia, KNH2 (supplying NH−2) is a strong base, and NH4NO3 (supplying NH+4) is a strong acid. In liquid sulfur dioxide (SO2), thionyl compounds (supplying SO2+) behave as acids, and sulfites (supplying SO2−3) behave as bases.
The non-aqueous acid–base reactions in liquid ammonia are similar to the reactions in water:
2
NaNH
2
base
+
Zn
(
NH
2
)
2
amphiphilic
amide
⟶
Na
2
[
Zn
(
NH
2
)
4
]
2
NH
4
I
acid
+
Zn
(
NH
2
)
2
⟶
[
Zn
(
NH
3
)
4
]
I
2
{\displaystyle {\begin{aligned}{\underset {\text{base}}{{\ce {2 NaNH2}}}}+{\underset {{\text{amphiphilic}} \atop {\text{amide}}}{{\ce {Zn(NH2)2}}}}&\longrightarrow {\ce {Na2[Zn(NH2)4]}}\\[4pt]{\underset {\text{acid}}{{\ce {2 NH4I}}}}\ +\ {\ce {Zn(NH2)2}}&\longrightarrow {\ce {[Zn(NH3)4]I2}}\end{aligned}}}
Nitric acid can be a base in liquid sulfuric acid:
HNO
3
base
+
2
H
2
SO
4
⟶
NO
2
+
+
H
3
O
+
+
2
HSO
4
−
{\displaystyle {\underset {\text{base}}{{\ce {HNO3}}}}+{\ce {2 H2SO4 -> NO2+ + H3O+ + 2 HSO4-}}}
The unique strength of this definition shows in describing the reactions in aprotic solvents; for example, in liquid N2O4:
AgNO
3
base
+
NOCl
acid
⟶
N
2
O
4
solvent
+
AgCl
salt
{\displaystyle {\underset {\text{base}}{{\ce {AgNO3}}}}+{\underset {\text{acid}}{{\ce {NOCl_{\ }}}}}\longrightarrow {\underset {\text{solvent}}{{\ce {N2O4}}}}+{\underset {\text{salt}}{{\ce {AgCl_{\ }}}}}}
Because the solvent system definition depends on the solute as well as on the solvent itself, a particular solute can be either an acid or a base depending on the choice of the solvent: HClO4 is a strong acid in water, a weak acid in acetic acid, and a weak base in fluorosulfonic acid; this characteristic of the theory has been seen as both a strength and a weakness, because some substances (such as SO3 and NH3) have been seen to be acidic or basic on their own right. On the other hand, solvent system theory has been criticized as being too general to be useful. Also, it has been thought that there is something intrinsically acidic about hydrogen compounds, a property not shared by non-hydrogenic solvonium salts.
=== Lux–Flood definition ===
This acid–base theory was a revival of the oxygen theory of acids and bases proposed by German chemist Hermann Lux in 1939, further improved by Håkon Flood c. 1947 and is still used in modern geochemistry and electrochemistry of molten salts. This definition describes an acid as an oxide ion (O2−) acceptor and a base as an oxide ion donor. For example:
(base)
(acid)
MgO
+
CO
2
⟶
MgCO
3
CaO
+
SiO
2
⟶
CaSiO
3
NO
3
−
+
S
2
O
7
2
−
⟶
NO
2
+
+
2
SO
4
2
−
{\displaystyle {\begin{array}{ccccl}_{\text{(base)}}&&_{\text{(acid)}}\\[4pt]{\ce {MgO}}&+&{\ce {CO2}}&\longrightarrow &{\ce {MgCO3}}\\[4pt]{\ce {CaO}}&+&{\ce {SiO2}}&\longrightarrow &{\ce {CaSiO3}}\\[4pt]{\ce {NO3-}}&+&{\ce {S2O7^2-}}\!\!&\longrightarrow &{\ce {NO2+ + 2 SO4^2-}}\end{array}}}
This theory is also useful in the systematisation of the reactions of noble gas compounds, especially the xenon oxides, fluorides, and oxofluorides.
=== Usanovich definition ===
Mikhail Usanovich developed a general theory that does not restrict acidity to hydrogen-containing compounds, but his approach, published in 1938, was even more general than Lewis theory. Usanovich's theory can be summarized as defining an acid as anything that accepts negative species or donates positive ones, and a base as the reverse. This defined the concept of redox (oxidation-reduction) as a special case of acid–base reactions.
Some examples of Usanovich acid–base reactions include:
(base)
(acid)
Na
2
O
+
SO
3
⟶
2
Na
+
+
SO
4
2
−
(species exchanged:
O
2
−
anion)
3
(
NH
4
)
2
S
+
Sb
2
S
5
⟶
6
NH
4
+
+
2
SbS
4
3
−
(species exchanged:
3
S
2
−
anions)
2
Na
+
Cl
2
⟶
2
Na
+
+
2
Cl
−
(species exchanged: 2 electrons)
{\displaystyle {\begin{array}{ccccll}_{\text{(base)}}&&_{\text{(acid)}}\\[4pt]{\ce {Na2O}}&+&{\ce {SO3}}&\longrightarrow &{\ce {2Na+{}+\ SO4^{2}-}}&{\text{(species exchanged: }}{\ce {O^{2}-}}{\text{anion)}}\\[4pt]{\ce {3(NH4)2S}}&+&{\ce {Sb2S5}}&\longrightarrow &{\ce {6NH4+{}+\ 2SbS4^{3}-}}&{\text{(species exchanged: }}{\ce {3S^{2}-}}{\text{ anions)}}\\[4pt]{\ce {2Na}}&+&{\ce {Cl2}}&\longrightarrow &{\ce {2Na+{}+\ 2Cl-}}&{\text{(species exchanged: 2 electrons)}}\end{array}}}
== Rationalizing the strength of Lewis acid–base interactions ==
=== HSAB theory ===
In 1963, Ralph Pearson proposed a qualitative concept known as the Hard and Soft Acids and Bases principle. later made quantitative with help of Robert Parr in 1984. 'Hard' applies to species that are small, have high charge states, and are weakly polarizable. 'Soft' applies to species that are large, have low charge states and are strongly polarizable. Acids and bases interact, and the most stable interactions are hard–hard and soft–soft. This theory has found use in organic and inorganic chemistry.
=== ECW model ===
The ECW model created by Russell S. Drago is a quantitative model that describes and predicts the strength of Lewis acid base interactions, −ΔH. The model assigned E and C parameters to many Lewis acids and bases. Each acid is characterized by an EA and a CA. Each base is likewise characterized by its own EB and CB. The E and C parameters refer, respectively, to the electrostatic and covalent contributions to the strength of the bonds that the acid and base will form. The equation is
−
Δ
H
=
E
A
E
B
+
C
A
C
B
+
W
{\displaystyle -\Delta H=E_{\rm {A}}E_{\rm {B}}+C_{\rm {A}}C_{\rm {B}}+W}
The W term represents a constant energy contribution for acid–base reaction such as the cleavage of a dimeric acid or base. The equation predicts reversal of acids and base strengths. The graphical presentations of the equation show that there is no single order of Lewis base strengths or Lewis acid strengths.
== Acid–base equilibrium ==
The reaction of a strong acid with a strong base is essentially a quantitative reaction. For example,
HCl
(
aq
)
+
Na
(
OH
)
(
aq
)
⟶
H
2
O
+
NaCl
(
aq
)
{\displaystyle {\ce {HCl_{(aq)}{}+ Na(OH)_{(aq)}-> H2O + NaCl_{(aq)}}}}
In this reaction both the sodium and chloride ions are spectators as the neutralization reaction,
H
+
OH
−
⟶
H
2
O
{\displaystyle {\ce {H + OH- -> H2O}}}
does not involve them. With weak bases addition of acid is not quantitative because a solution of a weak base is a buffer solution. A solution of a weak acid is also a buffer solution. When a weak acid reacts with a weak base an equilibrium mixture is produced. For example, adenine, written as AH, can react with a hydrogen phosphate ion, HPO2−4.
AH
+
HPO
4
2
−
↽
−
−
⇀
A
−
+
H
2
PO
4
−
{\displaystyle {\ce {AH + HPO4^2- <=> A- + H2PO4-}}}
The equilibrium constant for this reaction can be derived from the acid dissociation constants of adenine and of the dihydrogen phosphate ion.
[
A
−
]
[
H
+
]
=
K
a
1
[
AH
]
[
HPO
4
2
−
]
[
H
+
]
=
K
a
2
[
H
2
PO
4
−
]
{\displaystyle {\begin{aligned}\left[{\ce {A-}}\right]\!\left[{\ce {H+}}\right]&=K_{a1}{\bigl [}{\ce {AH}}{\bigr ]}\\[4pt]\left[{\ce {HPO4^2-}}\right]\!\left[{\ce {H+}}\right]&=K_{a2}\left[{\ce {H2PO4-}}\right]\end{aligned}}}
The notation [X] signifies "concentration of X". When these two equations are combined by eliminating the hydrogen ion concentration, an expression for the equilibrium constant, K is obtained.
[
A
−
]
[
H
2
PO
4
−
]
=
K
[
AH
]
[
HPO
4
2
−
]
;
K
=
K
a
1
K
a
2
{\displaystyle \left[{\ce {A-}}\right]\!\left[{\ce {H2PO4-}}\right]=K{\bigl [}{\ce {AH}}{\bigr ]}\!\left[{\ce {HPO4^2-}}\right];\quad K={\frac {K_{a1}}{K_{a2}}}}
== Acid–alkali reaction ==
An acid–alkali reaction is a special case of an acid–base reaction, where the base used is also an alkali. When an acid reacts with an alkali salt (a metal hydroxide), the product is a metal salt and water. Acid–alkali reactions are also neutralization reactions.
In general, acid–alkali reactions can be simplified to
OH
(
aq
)
−
+
H
(
aq
)
+
⟶
H
2
O
{\displaystyle {\ce {OH_{(aq)}- + H+_{(aq)}-> H2O}}}
by omitting spectator ions.
Acids are in general pure substances that contain hydrogen cations (H+) or cause them to be produced in solutions. Hydrochloric acid (HCl) and sulfuric acid (H2SO4) are common examples. In water, these break apart into ions:
HCl
⟶
H
(
aq
)
+
+
Cl
(
aq
)
−
H
2
SO
4
⟶
H
(
aq
)
+
+
HSO
4
(
aq
)
−
{\displaystyle {\begin{aligned}{\ce {HCl}}&\longrightarrow {\ce {H_{(aq)}+ {}+ Cl_{(aq)}-}}\\[4pt]{\ce {H2SO4}}&\longrightarrow {\ce {H_{(aq)}+ {}+ HSO4_{\,(aq)}-}}\end{aligned}}}
The alkali breaks apart in water, yielding dissolved hydroxide ions:
NaOH
⟶
Na
(
aq
)
+
+
OH
(
aq
)
−
{\displaystyle {\ce {NaOH -> Na^+_{(aq)}{}+ OH_{(aq)}-}}}
.
== See also ==
Acid–base titration
Deprotonation
Donor number
Electron configuration
Gutmann–Beckett method
Lewis structure
Nucleophilic substitution
Neutralization (chemistry)
Protonation
Redox reactions
Resonance (chemistry)
== Notes ==
== References ==
=== Sources ===
Clayden, Jonathan; Greeves, Nick; Warren, Stuart; Wothers, Peter (2015). Organic Chemistry (First ed.). Oxford University Press.
Finston, H.L.; Rychtman, A.C. (1983). A New View of Current Acid–Base Theories. New York: John Wiley & Sons.
Meyers, R. (2003). The Basics of Chemistry. Greenwood Press.
Miessler, G.L.; Tarr, D.A. (1991). Inorganic Chemistry.
== External links ==
Acid–base Physiology – an on-line text
John W. Kimball's online biology book section of acid and bases. | Wikipedia/Arrhenius_theory |
In chemistry, the ECW model is a semi-quantitative model that describes and predicts the strength of Lewis acid–Lewis base interactions. Many chemical reactions can be described as acid–base reactions, so models for such interactions are of potentially broad interest. The model initially assigned E and C parameters to each and every acid and base. The model was later expanded to the ECW model to cover reactions that have a constant energy term, W, which describes processes that precede the acid–base reaction. This quantitative model is often discussed with the qualitative HSAB theory, which also seeks to rationalize the behavior of diverse acids and bases.
== History of the problem ==
As early as 1938, G. N. Lewis pointed out that the relative strength of an acid or base depended upon the base or acid against which it was measured. No single rank order of acid or base strength can predict the energetics of the cross reaction. Consider the following pair of acid–base reactions:.
4F-C6H4OH + OEt2 −ΔH = 5.94 kcal/mole
4F-C6H4OH + SMe2 −ΔH = 4.73 kcal/mole
These data suggest that OEt2 is a stronger base than SMe2. The opposite is found, however, when I2 is the acid:
I2 + OEt2 −ΔH = 4.16 kcal/mole
I2 + SMe2 −ΔH = 7.63 kcal/mole
== E and C equation ==
The E-C model accommodates the failure of single parameter descriptions of acids and bases. In 1965 Russell S. Drago and Bradford Wayland published the two term equation such that each acid and each base is described by two parameters. Each acid is characterized by an EA and a CA. Each base is likewise characterized by its own EB and CB. The E and C parameters refer, respectively, to the electrostatic and covalent contributions to the strength of the bonds that the acid and base will form. These parameters have been empirically obtained by using enthalpies for adducts that form only σ bonds between the acid and base as well as adducts that have no steric repulsion between the acid and base.
−
Δ
H
=
E
A
E
B
+
C
A
C
B
{\displaystyle -\Delta H=E_{A}E_{B}+C_{A}C_{B}}
This equation reproduces and predicts the enthalpy, ΔH, of a reaction between many acids and bases. ΔH is a measure of strength of the bond between the acid and the base, both in the gas phase and in weakly solvating media. Entropy effects are ignored. A matrix presentation of the equation enhances its utility.
Four values, two E and two C were assigned as references. EA and CA of I2 were chosen as standards. Since I2 has little tendency to undergo electrostatic bonding, the EA parameter was assigned a small value, 0.5, while the value of CA for the covalent property was set at 2.0. For the two base parameters, EB for CH3C(O)N(CH3)2 (DMA) was set at 2.35 and CB for (C2H5)2S, diethyl sulfide, was set at 3.92. Fixing the parameters in this way imposed the covalent-electrostatic model on the data set by fixing the EAEB and CACB products of the DMA and (C2H5)2S adducts with iodine, and these four values ensured that none of the parameters had negative values. Due to increasing enthalpy data that became available since the EC equation was first proposed the parameters have been improved. Mixing E and C numbers from the improved set of parameters with older parameters will result in incorrect calculations and is to be avoided. A select set of the improved E and C numbers is found in this article and the complete set is available in the literature.
EB and CB parameters for phosphines that can be used in combination with the improved parameters for oxygen, nitrogen, and sulfur donors to measure σ-basicity have been reported.
== ECW model ==
In the ECW model, a new term W was added to the equation.
−
Δ
H
=
E
A
E
B
+
C
A
C
B
+
W
{\displaystyle -\Delta H=E_{A}E_{B}+C_{A}C_{B}+W}
The W term represents a constant energy for cleavage of a dimeric acid or base. For example, the enthalpy of cleavage the [Rh(CO)2Cl]2 by base B involves two steps. The first step is cleavage of the dimer, which is W:
1/2 [Rh(CO)2Cl]2 → Rh(CO)2Cl W = −10.39 kcal/mol
The second step is the binding of B to RhCl(CO)2 monomer. In this case, W = −10.39 kcal/mol.
In other cases, W is the enthalpy needed to cleave the internal hydrogen bonding of the H-bonding acid (CF3)3COH. W is also useful for a base displacement reaction in poorly solvating media:
F3B-OEt2 → BF3 + OEt2
For any base, a constant energy contribution is observed for the breaking of the F3B-OEt2 bond. An ECW study of the enthalpies of a series of bases produces a W value that corresponds to the enthalpy of dissociation of the F3B-OEt2 bond. The EA and CA parameters that result are those for uncomplexed BF3.
== A graphical presentation of the ECW model ==
A graphical presentation of this model clearly shows that there is no single rank order of acid or base strength, a point often overlooked, and emphasizes that the magnitude of acid and base interactions requires two parameters (E & C) to account for the interactions.
The EC equation from the ECW Model
−
Δ
H
=
E
A
E
B
+
C
A
C
B
{\displaystyle -\Delta H=E_{A}E_{B}+C_{A}C_{B}}
can be rearranged into a form which can be plotted as a straight line.
In a Cramer–Bopp plot for Lewis bases, the parameter Ra reflects the mode of bonding of a potential Lewis acid partner, from purely electrostatic interactions (Ra = −1) to purely covalent interactions (Ra = +1). The parameter
−
Δ
H
E
a
+
C
a
{\displaystyle \scriptstyle {\frac {-\Delta H}{E_{a}+C_{a}}}}
reflects the strength of the bonding interaction. The plot shown here allows comparison of three chosen Lewis bases: acetonitrile, ammonia, and dimethyl sulfide. The Lewis acid iodine (Ra = 0.6) will interact most strongly with dimethyl sulfide and least strongly with acetonitrile, whereas triethylgallium (Ra = −0.65) will interact most strongly with ammonia and least strongly with dimethyl sulfide. The plot also shows that ammonia is a stronger Lewis base than acetonitrile irrespective of its Lewis acid partner, whereas the relative strengths of ammonia and dimethyl sulfide as Lewis bases depends on the bonding characteristics of the Lewis acid, swapping order when Ra = 0.1. (NB: guesstimate). The Cramer–Bopp plot was developed as a visual tool for comparing Lewis base strength with the range of possible Lewis acid partners, and a similar plot can be constructed to examine selected Lewis acids against the range of possible Lewis bases. References 5, 8, 12, and 14 contain graphical presentations that define the ranking order of strength of many Lewis acids and bases.
== Other aspects and extensions of the ECW model ==
As mentioned above the E and C parameters are obtained from enthalpies of adduct formation in which the bond between the acid and base is a σ interaction and adducts that have no steric repulsion between the acid and base.
As a result, E and C parameters can be used to glean information about pi bonding. When pi bonding contributes to the measured enthalpy, the enthalpy calculated from the E and C parameters will be less than the measured enthalpy and the difference provides a measure of the extent of the pi bonding contribution.
The ᐃH calculated for the reaction of Me3B with Me3N is larger than the observed. This discrepancy is attributed to steric repulsion between the methyl groups on the B and N. The difference between the calculated and observed values can then be taken as the amount of the steric effect, a value otherwise not attainable. Steric effects have also been identified with (CH3)3SnCl and with Cu(HFacac)2.
The use of E and C parameters have been extended to analyze spectroscopic changes occurring during adduct formation. For example, the shift of the phenol OH stretching frequency, Δχ, that occurs upon adduct formation has been analyzed using the following equation:
Δχ = ΕA∗EB + CA∗CB + W∗
where asterisks on the EA and CA for phenol indicate that the acceptor is held constant and the frequency shift is measured as the base is varied. The asterisks also indicate that the phenol parameters are those for frequency shifts and not those for enthalpies. An analysis like this provides a basis for using EB and CB parameters as a reference scale of donor strengths for frequency shifts. This type analysis has also been applied to other spectroscopic shifts (NMR, EPR, UV-vis, IR, etc.) accompanying adduct formation. Any physicochemical property, Δχ, that is dominated by σ donor-acceptor interaction can be correlated with the enthalpy-derived E and C parameters.
The ECW equations enables one to correlate and predict the enthalpies of adduct formation of neutral donor-acceptor interactions for which the electron-transfer is limited. For gas-phase reactions between cations and neutral donors, there is significant electron-transfer. The extension of the ECW model to cation-neutral Lewis base interactions has led to the ECT model. Others have concluded that the ECW model "is generally found helpful in many fields of solution chemistry and biochemistry".
== Charge-transfer complexes of I2 ==
The enthalpies of formation of some Donor-I2 adducts are listed below. I2 is a Lewis acid classified as a soft acid and its acceptor properties are discussed in the ECW model. The relative acceptor strength of I2 toward a series of bases, versus other Lewis acids, can be illustrated by C-B plots.
== See also ==
Acid–base reaction
Lewis acid–Lewis base
Acid
Russell S. Drago
== Notes ==
== References == | Wikipedia/ECW_model |
A frustrated Lewis pair (FLP) is a compound or mixture containing a Lewis acid and a Lewis base that, because of steric hindrance, cannot combine to form a classical adduct. Many kinds of FLPs have been devised, and many simple substrates exhibit activation.
The discovery that some FLPs split H2 triggered a rapid growth of research into FLPs. Because of their "unquenched" reactivity, such systems are reactive toward substrates that can undergo heterolysis. For example, many FLPs split hydrogen molecules.
Thus, a mixture of tricyclohexylphosphine (PCy3) and tris(pentafluorophenyl)borane reacts with hydrogen to give the respective phosphonium and borate ions:
PCy3 + B(C6F5)3 + H2 → [HPCy3]+ [HB(C6F5)3]−
This reactivity has been exploited to produce FLPs which catalyse hydrogenation reactions.
== Small molecule activation ==
Frustrated Lewis pairs have been shown to activate many small molecules, either by inducing heterolysis or by coordination.
=== Hydrogen ===
The discovery that some FLPs are able to split, and therefore activate, H2 triggered a rapid growth of research into this area. The activation and therefore use of H2 is important for many chemical and biological transformations. Using FLPs to liberate H2 is metal-free, this is beneficial due to the cost and limited supply of some transition metals commonly used to activate H2 (Ni, Pd, Pt). FLP systems are reactive toward substrates that can undergo heterolysis (e.g. hydrogen) due to the "unquenched" reactivity of such systems. For example, it has been previously shown that a mixture of tricyclohexylphosphine (PCy3) and tris(pentafluorophenyl)borane reacts with H2 to give the respective phosphonium and borate ions:
PCy3 + B(C6F5)3 + H2 → [HPCy3]+ [HB(C6F5)3]−
In this reaction, PCy3 (the Lewis base) and B(C6F5)3 (the Lewis acid) cannot form an adduct due to the steric hindrance from the bulky cyclohexyl and pentafluorophenyl groups. The proton on the phosphorus and hydride from the borate are now ‘activated’ and can subsequently be ‘delivered’ to an organic substrate, resulting in hydrogenation.
=== Mechanism of dihydrogen activation by FLP ===
The mechanism for the activation of H2 by FLPs has been discussed for both the intermolecular and intramolecular cases. Intermolecular FLPs are where the Lewis base is a separate molecule to the Lewis acid, it is thought that these individual molecules interact through secondary London dispersion interactions to bring the Lewis base and acid together (a pre-organisational effect) where small molecules may then interact with the FLPs. The experimental evidence for this type of interaction at the molecular level is unclear. However, there is supporting evidence for this type of interaction based on computational density functional theory studies. Intramolecular FLPs are where the Lewis acid and Lewis base are combined in one molecule by a covalent linker. Despite the improved ‘pre-organisational effects’, rigid intramolecular FLP frameworks are thought to have a reduced reactivity to small molecules due to a reduction in flexibility.
=== Other small molecule substrates ===
FLPs are also reactive toward many unsaturated substrates beyond H2. Some FLPs react with CO2, specifically in the deoxygenative reduction of CO2 to methane.
Ethene also reacts with FLPs:
PCy3 + B(C6F5)3 + C2H4 → Cy3P+CH2CH2B−(C6F5)3
For acid-base pairs to behave both nucleophilically and electrophilically at the same time offers a method for the ring-opening of cyclic ethers such as THF, 2,5-dihydrofuran, coumaran, and dioxane.
== Use in catalysis ==
=== Imine, nitrile and aziridine hydrogenation ===
Reduction of imines, nitriles, and aziridines to primary and secondary amines traditionally is effected by metal hydride reagents, e.g. lithium aluminium hydride and sodium cyanoborohydride. Hydrogenations of these unsaturated substrates can be effected by metal-catalyzed reactions. Metal-free catalytic hydrogenation was carried out using the phosphonium borate catalyst (R2PH)(C6F4)BH(C6F5)2 (R = 2,4,6-Me3C6H2) 1. This type of metal-free hydrogenation has the potential to replace high cost metal catalyst.
The mechanism of imine reduction is proposed to involve protonation at nitrogen giving the iminium salt. The basicity of the nitrogen centre determines the rate of reaction. More electron rich imines reduce at faster rates than electron poor imines. The resulting iminium center undergoes nucleophilic attack by the borohydride anion to form the amine. Small amines bind to the borane, quenching further reactions. This problem can be overcome using various methods: 1) Application of elevated temperatures 2) Using sterically bulky imine substituents 3) Protecting the imine with the B(C6F5)3group, which also serves as a Lewis acid promoter.
=== Enantioselective imine hydrogenation ===
A chiral boronate Lewis acid derived from (1R)-(+)-camphor forms a frustrated Lewis pair with tBu3P, which is isolable as a salt. This FLP catalyses the enantioselective hydrogenation of some aryl imines in high yield but modest ee (up to 83%).
Although conceptually interesting, the protocol suffers from lack of generality. It was found that increasing steric bulk of the imine substituents lead to decreased yield and ee of the amine product. methoxy-substituted imines exhibit superior yield and ee's.
=== Asymmetric hydrosilylations ===
Frustrated Lewis pairs of chiral alkenylboranes and phosphines are beneficial for asymmetric Piers-type hydrosilylations of 1,2-dicarbonyl compounds and alpha-keto esters, giving high yield and enantioselectivity. However, in comparison to conventional Piers-type hydrosilyations, asymmetric Piers-type hydrosilylations are not as well developed.
In the following example, the chiral alkenylborane is formed in situ from a chiral diyne and the HB(C6F5)2. Heterolytic cleavage of the Si-H bond from PhMe2SiH by the FLP catalyst forms a silylium and hydridoborate ionic complex.
=== Alkyne hydrogenation ===
Metal free hydrogenation of unactivated internal alkynes to cis-alkenes is readily achieved using FLP-based catalysts. The condition for this reaction were relatively mild utilising 2 bar of H2. In terms of mechanism, the alkyne material is first hydroborated and then the resulting vinylborane-based FLP can then activate dihydrogen. A protodeborylation step releases the cis-alkene product, which is obtained due to the syn-hydroborylation process, and regenerating the catalyst. While active for alkyne hydrogenation the FLP-based catalysts do not however facilitate the hydrogenation of alkenes to alkanes.
The reaction is a syn-hydroboration, and as a result a high cis selectivity is observed. At the final stage of the catalytic cycle the C6F5 group is cleaved more easily than an alkyl group, causing catalyst degradation rather than alkane release. The catalytic cycle has three steps:
Substrate binding (the hydroboration of alkyne)
H2 cleavage with vinylborane, followed by intramolecular protodeborylation of vinyl substituent, recovering N,N-Dimethyl-2-[(pentafluorophenyl)boryl]aniline
Release of the cis-alkene
With internal alkynes, a competitive reaction occurs where the proton bound to the nitrogen can be added to the fluorobenzenes. Therefore, this addition does not proceed that much, the formation of the alkene seems favoured.
But terminal alkynes do not bind to the boron through hydroboration but rather through C-H activation. Thus, the addition of the proton to the alkyne will result in the initial terminal alkyne. Hence this hydrogenation process is not suitable to terminal alkynes and will only give pentafluorobenzene.
The metal free hydrogenation of terminal alkynes to the respective alkenes was recently achieved using a pyridone borane based system. This system activates hydrogen readily at room temperature yielding a pyridone borane complex. Dissociation of this complex allows hydroboration of an alkyne by the free borane. Upon protodeborylation by the free pyridone the cis alkene is generated. Hydrogenation of terminal alkynes is possible with this system, because the C-H activation is reversible and competes with hydrogen activation.
=== Borylation ===
Amine-borane FLPs catalyse the borylation of electron-rich aromatic heterocycles (Scheme 1). The reaction is driven by release of hydrogen via C-H activation by the FLP. Aromatic borylations are often used in pharmaceutical development, particularly due to the abundance, low cost and low toxicity of boron compounds compared to noble metals.,
The substrate for the reaction has two main requirements, strongly linked to the mechanism of borylation. First, the substrate must be electron rich, exemplified by the absence of a reaction with thiophene, whereas its more electron rich derivatives - methoxythiophene and 3,4-ethylenedioxythiophene - can undergo a reaction with the amino-borane. Furthermore, substitution of 1-methylpyrrole (which can react) with the strongly electron withdrawing tertbutyloxycarbonyl (Boc) group at the 2-position completely inhibits the reaction. The second requirement is for the absence of basic amine groups in the substrate, which would otherwise form an unwanted adduct. This can be illustrated by the lack of a reaction with pyrrole, whereas both 1-methyl and N-benzylpyrrole derivatives are able to react.
Further work by the same authors revealed that simply piperidine as the amine R group (as opposed to tetramethylpiperidine, pictured above) accelerated the rate of reaction. Through kinetic and DFT studies the authors proposed that the C-H activation step was more facile than with larger substituents.
Dearomatisation can also be achieved under similar conditions but using N-tosyl indoles. Syn-hyrdoborylated indolines are obtained.
Borylation of S-H bonds in thiols by a dehydrogenative process has also been observed. Alcohols and amines such as tert-Butanol and tert-Butylamine form stable products that prevent catalysis due to a strong π-bond between the N/O atom's lone pair and boron, whereas the same is not true for thiols, thus allowing for successful catalysis. In addition, successful borylation of Se-H bonds has been achieved. In all cases, the formation of H2 gas is a strong driving force for the reactions.
== Carbon capture ==
FLP chemistry is conceptually relevant to carbon capture. Both an intermolecular (Scheme 1) and intramolecular (Scheme 2) FLP consisting of a phosphine and a borane were used to selectively capture and release carbon dioxide. When a solution of the FLP was covered by an atmosphere of CO2 at room temperature, the FLP-CO2 compound immediately precipitated as a white solid.
Heating the intermolecular FLP-CO2 compound in bromobenzene at 80 °C under vacuum for 5 hours caused the release of around half of the CO2 and regenerating the two constituent components of the FLP. After several more hours of sitting at room temperature under vacuum, total release of CO2 and FLP regeneration had occurred.
The intramolecular FLP-CO2 compound by contrast was stable as a solid at room temperature but fully decomposed at temperatures above -20 °C as a solution in dichloromethane releasing CO2 and regenerating the FLP molecule.
This method of FLP carbon capture can be adapted to work in flow chemistry systems.
== Frustrated radical pair ==
Frustrated radical pairs (FRPs) can result from a single electron transfer between the Lewis base and the Lewis acid (sometimes after photoactivation). They can be studied using EPR spectroscopy.
FRPs have been proposed as intermediates to some reactions of FLPs, like the activation of dihydrogen. Such mechanisms have later been rejected as the concentration of frustrated radical pairs due to the spontaneous single electron transfer between FLPs is insignificant, which can be deduced from the oxidation potential of the Lewis base and the reduction potential of the Lewis acid.
Frustrated radical pairs may have synthetic applications in homolytically activating chemical bonds, for instance, in C-H bond functionalization.
== References == | Wikipedia/Frustrated_Lewis_pair |
Atomic theory is the scientific theory that matter is composed of particles called atoms. The definition of the word "atom" has changed over the years in response to scientific discoveries. Initially, it referred to a hypothetical concept of there being some fundamental particle of matter, too small to be seen by the naked eye, that could not be divided. Then the definition was refined to being the basic particles of the chemical elements, when chemists observed that elements seemed to combine with each other in ratios of small whole numbers. Then physicists discovered that these particles had an internal structure of their own and therefore perhaps did not deserve to be called "atoms", but renaming atoms would have been impractical by that point.
Atomic theory is one of the most important scientific developments in history, crucial to all the physical sciences. At the start of The Feynman Lectures on Physics, physicist and Nobel laureate Richard Feynman offers the atomic hypothesis as the single most prolific scientific concept.
== Philosophical atomism ==
The basic idea that matter is made up of tiny indivisible particles is an old idea that appeared in many ancient cultures. The word atom is derived from the ancient Greek word atomos, which means "uncuttable". This ancient idea was based in philosophical reasoning rather than scientific reasoning. Modern atomic theory is not based on these old concepts. In the early 19th century, the scientist John Dalton noticed that chemical substances seemed to combine with each other by discrete and consistent units of weight, and he decided to use the word atom to refer to these units.
== Groundwork ==
Working in the late 17th century, Robert Boyle developed the concept of a chemical element as substance different from a compound.: 293
Near the end of the 18th century, a number of important developments in chemistry emerged without referring to the notion of an atomic theory. The first was Antoine Lavoisier who showed that compounds consist of elements in constant proportion, redefining an element as a substance which scientists could not decompose into simpler substances by experimentation. This brought an end to the ancient idea of the elements of matter being fire, earth, air, and water, which had no experimental support. Lavoisier showed that water can be decomposed into hydrogen and oxygen, which in turn he could not decompose into anything simpler, thereby proving these are elements. Lavoisier also defined the law of conservation of mass, which states that in a chemical reaction, matter does not appear nor disappear into thin air; the total mass remains the same even if the substances involved were transformed.: 293 Finally, there was the law of definite proportions, established by the French chemist Joseph Proust in 1797, which states that if a compound is broken down into its constituent chemical elements, then the masses of those constituents will always have the same proportions by weight, regardless of the quantity or source of the original compound. This definition distinguished compounds from mixtures.
== Dalton's law of multiple proportions ==
John Dalton studied data gathered by himself and by other scientists. He noticed a pattern that later came to be known as the law of multiple proportions: in compounds which contain two particular elements, the amount of Element A per measure of Element B will differ across these compounds by ratios of small whole numbers. This suggested that each element combines with other elements in multiples of a basic quantity.
In 1804, Dalton explained his atomic theory to his friend and fellow chemist Thomas Thomson, who published an explanation of Dalton's theory in his book A System of Chemistry in 1807. According to Thomson, Dalton's idea first occurred to him when experimenting with "olefiant gas" (ethylene) and "carburetted hydrogen gas" (methane). Dalton found that "carburetted hydrogen gas" contains twice as much hydrogen per measure of carbon as "olefiant gas", and concluded that a molecule of "olefiant gas" is one carbon atom and one hydrogen atom, and a molecule of "carburetted hydrogen gas" is one carbon atom and two hydrogen atoms. In reality, an ethylene molecule has two carbon atoms and four hydrogen atoms (C2H4), and a methane molecule has one carbon atom and four hydrogen atoms (CH4). In this particular case, Dalton was mistaken about the formulas of these compounds, but he got them right in the following examples:
Example 1 — tin oxides: Dalton identified two types of tin oxide. One is a grey powder that Dalton referred to as "the protoxide of tin", which is 88.1% tin and 11.9% oxygen. The other is a white powder which Dalton referred to as "the deutoxide of tin", which is 78.7% tin and 21.3% oxygen. Adjusting these figures, in the grey powder there is about 13.5 g of oxygen for every 100 g of tin, and in the white powder there is about 27 g of oxygen for every 100 g of tin. 13.5 and 27 form a ratio of 1:2. These compounds are known today as tin(II) oxide (SnO) and tin(IV) oxide (SnO2). In Dalton's terminology, a "protoxide" is a molecule containing a single oxygen atom, and a "deutoxide" molecule has two. The modern equivalents of his terms would be monoxide and dioxide.
Example 2 — iron oxides: Dalton identified two oxides of iron. There is one type of iron oxide that is a black powder which Dalton referred to as "the protoxide of iron", which is 78.1% iron and 21.9% oxygen. The other iron oxide is a red powder, which Dalton referred to as "the intermediate or red oxide of iron" which is 70.4% iron and 29.6% oxygen. Adjusting these figures, in the black powder there is about 28 g of oxygen for every 100 g of iron, and in the red powder there is about 42 g of oxygen for every 100 g of iron. 28 and 42 form a ratio of 2:3. These compounds are iron(II) oxide and iron(III) oxide and their formulas are FeO and Fe2O3 respectively. Iron(II) oxide's formula is normally written as FeO, but since it is a crystalline substance one could alternately write it as Fe2O2, and when we contrast that with Fe2O3, the 2:3 ratio stands out plainly. Dalton described the "intermediate oxide" as being "2 atoms protoxide and 1 of oxygen", which adds up to two atoms of iron and three of oxygen. That averages to one and a half atoms of oxygen for every iron atom, putting it midway between a "protoxide" and a "deutoxide".
Example 3 — nitrogen oxides: Dalton was aware of three oxides of nitrogen: "nitrous oxide", "nitrous gas", and "nitric acid". These compounds are known today as nitrous oxide, nitric oxide, and nitrogen dioxide respectively. "Nitrous oxide" is 63.3% nitrogen and 36.7% oxygen, which means it has 80 g of oxygen for every 140 g of nitrogen. "Nitrous gas" is 44.05% nitrogen and 55.95% oxygen, which means there is 160 g of oxygen for every 140 g of nitrogen. "Nitric acid" is 29.5% nitrogen and 70.5% oxygen, which means it has 320 g of oxygen for every 140 g of nitrogen. 80 g, 160 g, and 320 g form a ratio of 1:2:4. The formulas for these compounds are N2O, NO, and NO2.
Dalton defined an atom as being the "ultimate particle" of a chemical substance, and he used the term "compound atom" to refer to "ultimate particles" which contain two or more elements. This is inconsistent with the modern definition, wherein an atom is the basic particle of a chemical element and a molecule is an agglomeration of atoms. The term "compound atom" was confusing to some of Dalton's contemporaries as the word "atom" implies indivisibility, but he responded that if a carbon dioxide "atom" is divided, it ceases to be carbon dioxide. The carbon dioxide "atom" is indivisible in the sense that it cannot be divided into smaller carbon dioxide particles.
Dalton made the following assumptions on how "elementary atoms" combined to form "compound atoms" (what we today refer to as molecules). When two elements can only form one compound, he assumed it was one atom of each, which he called a "binary compound". If two elements can form two compounds, the first compound is a binary compound and the second is a "ternary compound" consisting of one atom of the first element and two of the second. If two elements can form three compounds between them, then the third compound is a "quaternary" compound containing one atom of the first element and three of the second. Dalton thought that water was a "binary compound", i.e. one hydrogen atom and one oxygen atom. Dalton did not know that in their natural gaseous state, the ultimate particles of oxygen, nitrogen, and hydrogen exist in pairs (O2, N2, and H2). Nor was he aware of valencies. These properties of atoms were discovered later in the 19th century.
Because atoms were too small to be directly weighed using the methods of the 19th century, Dalton instead expressed the weights of the myriad atoms as multiples of the hydrogen atom's weight, which Dalton knew was the lightest element. By his measurements, 7 grams of oxygen will combine with 1 gram of hydrogen to make 8 grams of water with nothing left over, and assuming a water molecule to be one oxygen atom and one hydrogen atom, he concluded that oxygen's atomic weight is 7. In reality it is 16. Aside from the crudity of early 19th century measurement tools, the main reason for this error was that Dalton didn't know that the water molecule in fact has two hydrogen atoms, not one. Had he known, he would have doubled his estimate to a more accurate 14. This error was corrected in 1811 by Amedeo Avogadro. Avogadro proposed that equal volumes of any two gases, at equal temperature and pressure, contain equal numbers of molecules (in other words, the mass of a gas's particles does not affect the volume that it occupies). Avogadro's hypothesis, now usually called Avogadro's law, provided a method for deducing the relative weights of the molecules of gaseous elements, for if the hypothesis is correct relative gas densities directly indicate the relative weights of the particles that compose the gases. This way of thinking led directly to a second hypothesis: the particles of certain elemental gases were pairs of atoms, and when reacting chemically these molecules often split in two. For instance, the fact that two liters of hydrogen will react with just one liter of oxygen to produce two liters of water vapor (at constant pressure and temperature) suggested that a single oxygen molecule splits in two in order to form two molecules of water. The formula of water is H2O, not HO. Avogadro measured oxygen's atomic weight to be 15.074.
== Opposition to atomic theory ==
Dalton's atomic theory attracted widespread interest but not everyone accepted it at first. The law of multiple proportions was shown not to be a universal law when it came to organic substances, whose molecules can be quite large. For instance, in oleic acid there is 34 g of hydrogen for every 216 g of carbon, and in methane there is 72 g of hydrogen for every 216 g of carbon. 34 and 72 form a ratio of 17:36, which is not a ratio of small whole numbers. We know now that carbon-based substances can have very large molecules, larger than any the other elements can form. Oleic acid's formula is C18H34O2 and methane's is CH4. The law of multiple proportions by itself was not complete proof, and atomic theory was not universally accepted until the end of the 19th century.
One problem was the lack of uniform nomenclature. The word "atom" implied indivisibility, but Dalton defined an atom as being the ultimate particle of any chemical substance, not just the elements or even matter per se. This meant that "compound atoms" such as carbon dioxide could be divided, as opposed to "elementary atoms". Dalton disliked the word "molecule", regarding it as "diminutive". Amedeo Avogadro did the opposite: he exclusively used the word "molecule" in his writings, eschewing the word "atom", instead using the term "elementary molecule". Jöns Jacob Berzelius used the term "organic atoms" to refer to particles containing three or more elements, because he thought this only existed in organic compounds. Jean-Baptiste Dumas used the terms "physical atoms" and "chemical atoms"; a "physical atom" was a particle that cannot be divided by physical means such as temperature and pressure, and a "chemical atom" was a particle that could not be divided by chemical reactions.
The modern definitions of atom and molecule—an atom being the basic particle of an element, and a molecule being an agglomeration of atoms—were established in the late half of the 19th century. A key event was the Karlsruhe Congress in Germany in 1860. As the first international congress of chemists, its goal was to establish some standards in the community. A major proponent of the modern distinction between atoms and molecules was Stanislao Cannizzaro.
The various quantities of a particular element involved in the constitution of different molecules are integral multiples of a fundamental quantity that always manifests itself as an indivisible entity and which must properly be named atom.
Cannizzaro criticized past chemists such as Berzelius for not accepting that the particles of certain gaseous elements are actually pairs of atoms, which led to mistakes in their formulation of certain compounds. Berzelius believed that hydrogen gas and chlorine gas particles are solitary atoms. But he observed that when one liter of hydrogen reacts with one liter of chlorine, they form two liters of hydrogen chloride instead of one. Berzelius decided that Avogadro's law does not apply to compounds. Cannizzaro preached that if scientists just accepted the existence of single-element molecules, such discrepancies in their findings would be easily resolved. But Berzelius did not even have a word for that. Berzelius used the term "elementary atom" for a gas particle which contained just one element and "compound atom" for particles which contained two or more elements, but there was nothing to distinguish H2 from H since Berzelius did not believe in H2. So Cannizzaro called for a redefinition so that scientists could understand that a hydrogen molecule can split into two hydrogen atoms in the course of a chemical reaction.
A second objection to atomic theory was philosophical. Scientists in the 19th century had no way of directly observing atoms. They inferred the existence of atoms through indirect observations, such as Dalton's law of multiple proportions. Some scientists adopted positions aligned with the philosophy of positivism, arguing that scientists should not attempt to deduce the deeper reality of the universe, but only systemize what patterns they could directly observe.: 232
This generation of anti-atomists can be grouped in two camps.
The "equivalentists", like Marcellin Berthelot, believed the theory of equivalent weights was adequate for scientific purposes. This generalization of Proust's law of definite proportions summarized observations. For example, 1 gram of hydrogen will combine with 8 grams of oxygen to form 9 grams of water, therefore the "equivalent weight" of oxygen is 8 grams. The "energeticist", like Ernst Mach and Wilhelm Ostwald, were philosophically opposed to hypothesis about reality altogether. In their view, only energy as part of thermodynamics should be the basis of physical models.: 237
These positions were eventually quashed by two important advancements that happened later in the 19th century: the development of the periodic table and the discovery that molecules have an internal architecture that determines their properties.
== Isomerism ==
Scientists discovered some substances have the exact same chemical content but different properties. For instance, in 1827, Friedrich Wöhler discovered that silver fulminate and silver cyanate are both 107 parts silver, 12 parts carbon, 14 parts nitrogen, and 16 parts oxygen (we now know their formulas as both AgCNO). In 1830 Jöns Jacob Berzelius introduced the term isomerism to describe the phenomenon. In 1860, Louis Pasteur hypothesized that the molecules of isomers might have the same set of atoms but in different arrangements.
In 1874, Jacobus Henricus van 't Hoff proposed that the carbon atom bonds to other atoms in a tetrahedral arrangement. Working from this, he explained the structures of organic molecules in such a way that he could predict how many isomers a compound could have. Consider, for example, pentane (C5H12). In van 't Hoff's way of modelling molecules, there are three possible configurations for pentane, and scientists did go on to discover three and only three isomers of pentane.
Isomerism was not something that could be fully explained by alternative theories to atomic theory, such as radical theory and the theory of types.
== Mendeleev's periodic table ==
Dmitrii Mendeleev noticed that when he arranged the elements in a row according to their atomic weights, there was a certain periodicity to them.: 117 For instance, the second element, lithium, had similar properties to the ninth element, sodium, and the sixteenth element, potassium — a period of seven. Likewise, beryllium, magnesium, and calcium were similar and all were seven places apart from each other on Mendeleev's table. Using these patterns, Mendeleev predicted the existence and properties of new elements, which were later discovered in nature: scandium, gallium, and germanium.: 118 Moreover, the periodic table could predict how many atoms of other elements that an atom could bond with — e.g., germanium and carbon are in the same group on the table and their atoms both combine with two oxygen atoms each (GeO2 and CO2). Mendeleev found these patterns validated atomic theory because it showed that the elements could be categorized by their atomic weight. Inserting a new element into the middle of a period would break the parallel between that period and the next, and would also violate Dalton's law of multiple proportions.
The elements on the periodic table were originally arranged in order of increasing atomic weight. However, in a number of places chemists chose to swap the positions of certain adjacent elements so that they appeared in a group with other elements with similar properties. For instance, tellurium is placed before iodine even though tellurium is heavier (127.6 vs 126.9) so that iodine can be in the same column as the other halogens. The modern periodic table is based on atomic number, which is equivalent to the nuclear charge, a change had to wait for the discovery of the nucleus.: 228
In addition, an entire row of the table was not shown
because the noble gases had not been discovered when Mendeleev devised his table.: 222
== Statistical mechanics ==
In 1738, Swiss physicist and mathematician Daniel Bernoulli postulated that the pressure of gases and heat were both caused by the underlying motion of particles. Using his model he could predict the ideal gas law at constant temperature and suggested that the temperature was proportional to the velocity of the particles. These results were largely ignored for a century.: 25
James Clerk Maxwell, a vocal proponent of atomism, revived the kinetic theory in 1860 and 1867. His key insight was that the velocity of particles in a gas would vary around an average value, introducing the concept of a distribution function.: 26 Ludwig Boltzmann and Rudolf Clausius expanded his work on gases and the laws of thermodynamics especially the second law relating to entropy. In the 1870s, Josiah Willard Gibbs extended the laws of entropy and thermodynamics and coined the term "statistical mechanics."
Boltzmann defended the atomistic hypothesis against major detractors from the time like Ernst Mach or energeticists like Wilhelm Ostwald, who considered that energy was the elementary quantity of reality.
At the beginning of the 20th century, Albert Einstein independently reinvented Gibbs' laws, because they had only been printed in an obscure American journal. Einstein later commented that had he known of Gibbs' work, he would "not have published those papers at all, but confined myself to the treatment of some few points [that were distinct]." All of statistical mechanics and the laws of heat, gas, and entropy took the existence of atoms as a necessary postulate.
=== Brownian motion ===
In 1827, the British botanist Robert Brown observed that dust particles inside pollen grains floating in water constantly jiggled about for no apparent reason. In 1905, Einstein theorized that this Brownian motion was caused by the water molecules continuously knocking the grains about, and developed a mathematical model to describe it. This model was validated experimentally in 1908 by French physicist Jean Perrin, who used Einstein's equations to measure the size of atoms.
== Discovery of the electron ==
Atoms were thought to be the smallest possible division of matter until 1899 when J. J. Thomson discovered the electron through his work on cathode rays.: 86 : 364
A Crookes tube is a sealed glass container in which two electrodes are separated by a vacuum. When a voltage is applied across the electrodes, cathode rays are generated, creating a glowing patch where they strike the glass at the opposite end of the tube. Through experimentation, Thomson discovered that the rays could be deflected by electric fields and magnetic fields, which meant that these rays were not a form of light but were composed of very light charged particles, and their charge was negative. Thomson called these particles "corpuscles". He measured their mass-to-charge ratio to be several orders of magnitude smaller than that of the hydrogen atom, the smallest atom. This ratio was the same regardless of what the electrodes were made of and what the trace gas in the tube was.
In contrast to those corpuscles, positive ions created by electrolysis or X-ray radiation had mass-to-charge ratios that varied depending on the material of the electrodes and the type of gas in the reaction chamber, indicating they were different kinds of particles.: 363
In 1898, Thomson measured the charge on ions to be roughly 6 × 10−10 electrostatic units (2 × 10−19 Coulombs).: 85 In 1899, he showed that negative electricity created by ultraviolet light landing on a metal (known now as the photoelectric effect) has the same mass-to-charge ratio as cathode rays; then he applied his previous method for determining the charge on ions to the negative electric particles created by ultraviolet light.: 86 By this combination he showed that electron's mass was 0.0014 times that of hydrogen ions. These "corpuscles" were so light yet carried so much charge that Thomson concluded they must be the basic particles of electricity, and for that reason other scientists decided that these "corpuscles" should instead be called electrons following an 1894 suggestion by George Johnstone Stoney for naming the basic unit of electrical charge.
In 1904, Thomson published a paper describing a new model of the atom. Electrons reside within atoms, and they transplant themselves from one atom to the next in a chain in the action of an electrical current. When electrons do not flow, their negative charge logically must be balanced out by some source of positive charge within the atom so as to render the atom electrically neutral. Having no clue as to the source of this positive charge, Thomson tentatively proposed that the positive charge was everywhere in the atom, the atom being shaped like a sphere—this was the mathematically simplest model to fit the available evidence (or lack of it). The balance of electrostatic forces would distribute the electrons throughout this sphere in a more or less even manner. Thomson further explained that ions are atoms that have a surplus or shortage of electrons.
Thomson's model is popularly known as the plum pudding model, based on the idea that the electrons are distributed throughout the sphere of positive charge with the same density as raisins in a plum pudding. Neither Thomson nor his colleagues ever used this analogy. It seems to have been a conceit of popular science writers. The analogy suggests that the positive sphere is like a solid, but Thomson likened it to a liquid, as he proposed that the electrons moved around in it in patterns governed by the electrostatic forces. Thus the positive electrification in Thomson's model was a temporary concept. Thomson's model was incomplete, it could not predict any of the known properties of the atom such as emission spectra or valencies.
In 1906, Robert A. Millikan and Harvey Fletcher performed the oil drop experiment in which they measured the charge of an electron to be about -1.6 × 10−19, a value now defined as -1 e. Since the hydrogen ion and the electron were known to be indivisible and a hydrogen atom is neutral in charge, it followed that the positive charge in hydrogen was equal to this value, i.e. 1 e.
== Discovery of the nucleus ==
Thomson's plum pudding model was challenged in 1911 by one of his former students, Ernest Rutherford, who presented a new model to explain new experimental data. The new model proposed a concentrated center of charge and mass that was later dubbed the atomic nucleus.: 296
Ernest Rutherford and his colleagues Hans Geiger and Ernest Marsden came to have doubts about the Thomson model after they encountered difficulties when they tried to build an instrument to measure the charge-to-mass ratio of alpha particles (these are positively-charged particles emitted by certain radioactive substances such as radium). The alpha particles were being scattered by the air in the detection chamber, which made the measurements unreliable. Thomson had encountered a similar problem in his work on cathode rays, which he solved by creating a near-perfect vacuum in his instruments. Rutherford didn't think he'd run into this same problem because alpha particles usually have much more momentum than electrons. According to Thomson's model of the atom, the positive charge in the atom is not concentrated enough to produce an electric field strong enough to deflect an alpha particle. Yet there was scattering, so Rutherford and his colleagues decided to investigate this scattering carefully.
Between 1908 and 1913, Rutherford and his colleagues performed a series of experiments in which they bombarded thin foils of metal with a beam of alpha particles. They spotted alpha particles being deflected by angles greater than 90°. According to Thomson's model, all of the alpha particles should have passed through with negligible deflection. Rutherford deduced that the positive charge of the atom is not distributed throughout the atom's volume as Thomson believed, but is concentrated in a tiny nucleus at the center. This nucleus also carries most of the atom's mass. Only such an intense concentration of charge, anchored by its high mass, could produce an electric field strong enough to deflect the alpha particles as observed. Rutherford's model, being supported primarily by scattering data unfamiliar to many scientists, did not catch on until Niels Bohr joined Rutherford's lab and developed a new model for the electrons.: 304
Rutherford model predicted that the scattering of alpha particles would be proportional to the square of the atomic charge. Geiger and Marsden's based their analysis on setting the charge to half of the atomic weight of the foil's material (gold, aluminium, etc.). Amateur physicist Antonius van den Broek noted that there was a more precise relation between the charge and the element's numeric sequence in the order of atomic weights. The sequence number came be called the atomic number and it replaced atomic weight in organizing the periodic table.
== Bohr model ==
Rutherford deduced the existence of the atomic nucleus through his experiments but he had nothing to say about how the electrons were arranged around it. In 1912, Niels Bohr joined Rutherford's lab and began his work on a quantum model of the atom.: 19
Max Planck in 1900 and Albert Einstein in 1905 had postulated that light energy is emitted or absorbed in discrete amounts known as quanta (singular, quantum). This led to a series of atomic models with some quantum aspects, such as that of Arthur Erich Haas in 1910: 197 and the 1912 John William Nicholson atomic model with quantized angular momentum as h/2π. The dynamical structure of these models was still classical, but in 1913, Bohr abandon the classical approach. He started his Bohr model of the atom with a quantum hypothesis: an electron could only orbit the nucleus in particular circular orbits with fixed angular momentum and energy, its distance from the nucleus (i.e., their radii) being proportional to its energy.: 197 Under this model an electron could not lose energy in a continuous manner; instead, it could only make instantaneous "quantum leaps" between the fixed energy levels. When this occurred, light was emitted or absorbed at a frequency proportional to the change in energy (hence the absorption and emission of light in discrete spectra).
In a trilogy of papers Bohr described and applied his model to derive the Balmer series of lines in the atomic spectrum of hydrogen and the related spectrum of He+.: 197 He also used he model to describe the structure of the periodic table and aspects of chemical bonding. Together these results lead to Bohr's model being widely accepted by the end of 1915.: 91
Bohr's model was not perfect. It could only predict the spectral lines of hydrogen, not those of multielectron atoms. Worse still, it could not even account for all features of the hydrogen spectrum: as spectrographic technology improved, it was discovered that applying a magnetic field caused spectral lines to multiply in a way that Bohr's model couldn't explain. In 1916, Arnold Sommerfeld added elliptical orbits to the Bohr model to explain the extra emission lines, but this made the model very difficult to use, and it still couldn't explain more complex atoms.
== Discovery of isotopes ==
While experimenting with the products of radioactive decay, in 1913 radiochemist Frederick Soddy discovered that there appeared to be more than one variety of some elements. The term isotope was coined by Margaret Todd as a suitable name for these varieties.
That same year, J. J. Thomson conducted an experiment in which he channeled a stream of neon ions through magnetic and electric fields, striking a photographic plate at the other end. He observed two glowing patches on the plate, which suggested two different deflection trajectories. Thomson concluded this was because some of the neon ions had a different mass. The nature of this differing mass would later be explained by the discovery of neutrons in 1932: all atoms of the same element contain the same number of protons, while different isotopes have different numbers of neutrons.
== Discovery of the proton ==
Back in 1815, William Prout observed that the atomic weights of the known elements were multiples of hydrogen's atomic weight, so he hypothesized that all atoms are agglomerations of hydrogen, a particle which he dubbed "the protyle". Prout's hypothesis was put into doubt when some elements were found to deviate from this pattern—e.g. chlorine atoms on average weigh 35.45 daltons—but when isotopes were discovered in 1913, Prout's observation gained renewed attention.
In 1898, J. J. Thomson found that the positive charge of a hydrogen ion was equal to the negative charge of a single electron.
In an April 1911 paper concerning his studies on alpha particle scattering, Ernest Rutherford estimated that the charge of an atomic nucleus, expressed as a multiplier of hydrogen's nuclear charge (qe), is roughly half the atom's atomic weight.
In June 1911, Van den Broek noted that on the periodic table, each successive chemical element increased in atomic weight on average by 2, which in turn suggested that each successive element's nuclear charge increased by 1 qe. In 1913, van den Broek further proposed that the electric charge of an atom's nucleus, expressed as a multiplier of the elementary charge, is equal to the element's sequential position on the periodic table. Rutherford defined this position as being the element's atomic number.
In 1913, Henry Moseley measured the X-ray emissions of all the elements on the periodic table and found that the frequency of the X-ray emissions was a mathematical function of the element's atomic number and the charge of a hydrogen nucleus (see Moseley's law).
In 1917 Rutherford bombarded nitrogen gas with alpha particles and observed hydrogen ions being emitted from the gas. Rutherford concluded that the alpha particles struck the nuclei of the nitrogen atoms, causing hydrogen ions to split off.
These observations led Rutherford to conclude that the hydrogen nucleus was a singular particle with a positive charge equal to that of the electron's negative charge. The name "proton" was suggested by Rutherford at an informal meeting of fellow physicists in Cardiff in 1920.
The charge number of an atomic nucleus was found to be equal to the element's ordinal position on the periodic table. The nuclear charge number thus provided a simple and clear-cut way of distinguishing the chemical elements from each other, as opposed to Lavoisier's classic definition of a chemical element being a substance that cannot be broken down into simpler substances by chemical reactions. The charge number or proton number was thereafter referred to as the atomic number of the element. In 1923, the International Committee on Chemical Elements officially declared the atomic number to be the distinguishing quality of a chemical element.
During the 1920s, some writers defined the atomic number as being the number of "excess protons" in a nucleus. Before the discovery of the neutron, scientists believed that the atomic nucleus contained a number of "nuclear electrons" which cancelled out the positive charge of some of its protons. This explained why the atomic weights of most atoms were higher than their atomic numbers. Helium, for instance, was thought to have four protons and two nuclear electrons in the nucleus, leaving two excess protons and a net nuclear charge of 2+. After the neutron was discovered, scientists realized the helium nucleus in fact contained two protons and two neutrons.
== Discovery of the neutron ==
Physicists in the 1920s believed that the atomic nucleus contained protons plus a number of "nuclear electrons" that reduced the overall charge. These "nuclear electrons" were distinct from the electrons that orbited the nucleus. This incorrect hypothesis would have explained why the atomic numbers of the elements were less than their atomic weights, and why radioactive elements emit electrons (beta radiation) in the process of nuclear decay. Rutherford even hypothesized that a proton and an electron could bind tightly together into a "neutral doublet". Rutherford wrote that the existence of such "neutral doublets" moving freely through space would provide a more plausible explanation for how the heavier elements could have formed in the genesis of the Universe, given that it is hard for a lone proton to fuse with a large atomic nucleus because of the repulsive electric field.
In 1928, Walter Bothe observed that beryllium emitted a highly penetrating, electrically neutral radiation when bombarded with alpha particles. It was later discovered that this radiation could knock hydrogen atoms out of paraffin wax. Initially it was thought to be high-energy gamma radiation, since gamma radiation had a similar effect on electrons in metals, but James Chadwick found that the ionization effect was too strong for it to be due to electromagnetic radiation, so long as energy and momentum were conserved in the interaction. In 1932, Chadwick exposed various elements, such as hydrogen and nitrogen, to the mysterious "beryllium radiation", and by measuring the energies of the recoiling charged particles, he deduced that the radiation was actually composed of electrically neutral particles which could not be massless like the gamma ray, but instead were required to have a mass similar to that of a proton. Chadwick called this new particle "the neutron" and believed that it to be a proton and electron fused together because the neutron had about the same mass as a proton and an electron's mass is negligible by comparison. Neutrons are not in fact a fusion of a proton and an electron.
== Modern quantum mechanical models ==
In 1924, Louis de Broglie proposed that all particles—particularly subatomic particles such as electrons—have an associated wave. Erwin Schrödinger, fascinated by this idea, developed an equation that describes an electron as a wave function instead of a point. This approach predicted many of the spectral phenomena that Bohr's model failed to explain, but it was difficult to visualize, and faced opposition. One of its critics, Max Born, proposed instead that Schrödinger's wave function did not describe the physical extent of an electron (like a charge distribution in classical electromagnetism), but rather gave the probability that an electron would, when measured, be found at a particular point. This reconciled the ideas of wave-like and particle-like electrons: the behavior of an electron, or of any other subatomic entity, has both wave-like and particle-like aspects, and whether one aspect or the other is observed depend upon the experiment.
A consequence of describing particles as waveforms rather than points is that it is mathematically impossible to calculate with precision both the position and momentum of a particle at a given point in time. This became known as the uncertainty principle, a concept first introduced by Werner Heisenberg in 1927.
Schrödinger's wave model for hydrogen replaced Bohr's model, with its neat, clearly defined circular orbits. The modern model of the atom describes the positions of electrons in an atom in terms of probabilities. An electron can potentially be found at any distance from the nucleus, but, depending on its energy level and angular momentum, exists more frequently in certain regions around the nucleus than others; this pattern is referred to as its atomic orbital. The orbitals come in a variety of shapes—sphere, dumbbell, torus, etc.—with the nucleus in the middle. The shapes of atomic orbitals are found by solving the Schrödinger equation. Analytic solutions of the Schrödinger equation are known for very few relatively simple model Hamiltonians including the hydrogen atom and the hydrogen molecular ion. Beginning with the helium atom—which contains just two electrons—numerical methods are used to solve the Schrödinger equation.
Qualitatively the shape of the atomic orbitals of multi-electron atoms resemble the states of the hydrogen atom. The Pauli principle requires the distribution of these electrons within the atomic orbitals such that no more than two electrons are assigned to any one orbital; this requirement profoundly affects the atomic properties and ultimately the bonding of atoms into molecules.: 182
== See also ==
== Footnotes ==
== Bibliography ==
Feynman, R.P.; Leighton, R.B.; Sands, M. (1963). The Feynman Lectures on Physics. Vol. 1. ISBN 978-0-201-02116-5. {{cite book}}: ISBN / Date incompatibility (help)
Andrew G. van Melsen (1960) [First published 1952]. From Atomos to Atom: The History of the Concept Atom. Translated by Henry J. Koren. Dover Publications. ISBN 0-486-49584-1. {{cite book}}: ISBN / Date incompatibility (help)
J. P. Millington (1906). John Dalton. J. M. Dent & Co. (London); E. P. Dutton & Co. (New York).
Jaume Navarro (2012). A History of the Electron: J. J. and G. P. Thomson. Cambridge University Press. ISBN 978-1-107-00522-8.
Trusted, Jennifer (1999). The Mystery of Matter. MacMillan. ISBN 0-333-76002-6.
Bernard Pullman (1998). The Atom in the History of Human Thought. Translated by Axel Reisinger. Oxford University Press. ISBN 0-19-511447-7.
Jean Perrin (1910) [1909]. Brownian Movement and Molecular Reality. Translated by F. Soddy. Taylor and Francis.
Ida Freund (1904). The Study of Chemical Composition. Cambridge University Press.
Thomas Thomson (1807). A System of Chemistry: In Five Volumes, Volume 3. John Brown.
Thomas Thomson (1831). The History of Chemistry, Volume 2. H. Colburn, and R. Bentley.
John Dalton (1808). A New System of Chemical Philosophy vol. 1.
John Dalton (1817). A New System of Chemical Philosophy vol. 2.
Stanislao Cannizzaro (1858). Sketch of a Course of Chemical Philosophy. The Alembic Club.
== Further reading ==
Charles Adolphe Wurtz (1881) The Atomic Theory, D. Appleton and Company, New York.
Alan J. Rocke (1984) Chemical Atomism in the Nineteenth Century: From Dalton to Cannizzaro, Ohio State University Press, Columbus (open access full text at http://digital.case.edu/islandora/object/ksl%3Ax633gj985).
== External links ==
Atomism by S. Mark Cohen.
Atomic Theory – detailed information on atomic theory with respect to electrons and electricity.
The Feynman Lectures on Physics Vol. I Ch. 1: Atoms in Motion | Wikipedia/Atomic_model |
Visual Molecular Dynamics (VMD) is a molecular modelling and visualization computer program. VMD is developed mainly as a tool to view and analyze the results of molecular dynamics simulations. It also includes tools for working with volumetric data, sequence data, and arbitrary graphics objects. Molecular scenes can be exported to external rendering tools such as POV-Ray, RenderMan, Tachyon, Virtual Reality Modeling Language (VRML), and many others. Users can run their own Tcl and Python scripts within VMD as it includes embedded Tcl and Python interpreters. VMD runs on Unix, Apple Mac macOS, and Microsoft Windows. VMD is available to non-commercial users under a distribution-specific license which permits both use of the program and modification of its source code, at no charge.
== History ==
VMD has been developed under the aegis of principal investigator Klaus Schulten in the Theoretical and Computational Biophysics group at the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana–Champaign. A precursor program, called VRChem, was developed in 1992 by Mike Krogh, William Humphrey, and Rick Kufrin. The initial version of VMD was written by William Humphrey, Andrew Dalke, Ken Hamer, Jon Leech, and James Phillips. It was released in 1995. The earliest versions of VMD were developed for Silicon Graphics workstations and could also run in a cave automatic virtual environment (CAVE) and communicate with a Nanoscale Molecular Dynamics (NAMD) simulation. VMD was further developed by A. Dalke, W. Humphrey, J. Ulrich in 1995–1996, followed by Sergei Izrailev and J. Stone during 1997–1998. In 1998, John Stone became the main VMD developer, porting VMD to many other Unix operating systems and completing the first full-featured OpenGL version. The first version of VMD for the Microsoft Windows platform was released in 1999. In 2001, Justin Gullingsrud, and Paul Grayson, and John Stone added support for haptic feedback devices and further developing the interface between VMD and NAMD for performing interactive molecular dynamics simulations. In subsequent developments, Jordi Cohen, Gullingsrud, and Stone entirely rewrote the graphical user interfaces, added built-in support for display and processing of volumetric data, and the use of OpenGL Shading Language.
== Interprocess communication ==
VMD can communicate with other programs via Tcl/Tk. This communication allows the development of several external plugins that works together with VMD. These plugins increases the set of features and tools of VMD making it one of the most used software in computational chemistry, biology, and biochemistry.
Here is a list of some VMD plugins developed using Tcl/Tk:
Delphi Force — electrostatic force calculation and visualization
Pathways Plugin — identify dominant electron transfer pathways and estimate donor-to-acceptor electronic tunneling
Check Sidechains Plugin — checks and helps select best orientation and protonation state for Asn, Gln, and His side chains
MultiMSMS Plugin — caches MSMS calculations to speedup the animation of a sequence of frames
Interactive Essential Dynamics — Interactive visualization of essential dynamics
Mead Ionize — Improved version of autoionize for highly charged systems
Andriy Anishkin's VMD Scripts — Many useful VMD scripts for visualization and analysis
RMSD Trajectory Tool — Development version of RMSD plugin for trajectories
Clustering Tool — Visualize clusters of conformations of a structure
iTrajComp — interactive Trajectory Comparison tool
Swap — Atomic coordinate swapping for improved RMSD alignment
Intervor — Protein-Protein interface extraction and display
SurfVol — Measure surface area and volume of proteins
vmdICE — Plugin for computing RMSD, RMSF, SASA, and other time-varying quantities
molUP - A VMD plugin to handle QM and ONIOM calculations using the gaussian software
VMD Store - A VMD extensions that helps users to discover, install, and update other VMD plugins.
== See also ==
== References ==
== External links ==
Official website
VMD on GPUs
Protein workbench STRAP | Wikipedia/Visual_Molecular_Dynamics |
Amsterdam Density Functional (ADF) is a program for first-principles electronic structure calculations that makes use of density functional theory (DFT). ADF was first developed in the early seventies by the group of E. J. Baerends from the Vrije Universiteit in Amsterdam, and by the group of T. Ziegler from the University of Calgary. Nowadays many other academic groups are contributing to the software. Software for Chemistry & Materials (SCM), formerly known as Scientific Computing & Modelling is a spin-off company from the Baerends group. SCM has been coordinating the development and distribution of ADF since 1995. Together with the rise in popularity of DFT in the nineties, ADF has become a popular computational chemistry software package used in the industrial and academic research. ADF excels in spectroscopy, transition metals, and heavy elements problems. A periodic structure counterpart of ADF named BAND is available to study bulk crystals, polymers, and surfaces. The Amsterdam Modeling Suite has expanded beyond DFT since 2010, with the semi-empirical MOPAC code, the Quantum ESPRESSO plane wave code, a density-functional based tight binding (DFTB) module, a reactive force field module ReaxFF, and an implementation of Klamt's COSMO-RS method, which also includes COSMO-SAC, UNIFAC, and QSPR.
== Specific features and capabilities ==
See ADF website for a comprehensive listing.
Slater-type orbitals (STOs) as basis functions for both molecular and periodic calculations, in contrast to Gaussian orbitals (GTOs) and plane waves in other codes.
Basis sets and relativistic methods (zeroth order regular approximation to the Dirac equation (ZORA), X2C: scalar relativistic and spin-orbit coupling) for all the chemical elements up to no. 118.
Various molecular properties: IR, Raman, VCD, UV, XAS spectra; NMR and EPR (ESR) parameters.
Solvent and environmental effects via COSMO, QM/MM, DRF, subsystem DFT.
Many chemical analysis tools (energy decomposition analysis, transfer integrals, (partial) density of states, etc.)
Periodic DFT with atomic orbitals: 1D, 2D, 3D and a graphical interface to plane wave code Quantum ESPRESSO
Thermodynamic properties of solvents and solutions (Solubility, LogP, VLE, LLE) with COSMO-RS
Semi-empirical modules MOPAC and DFTB
Parallelized ReaxFF with GUI for reactive molecular dynamics
Integrated graphical user interface (GUI) for all modules to set up calculations and visualize the results.
Out-of-the-box parallel calculations via IntelMPI, OpenMPI or native MPI. Limited GPU support
== See also ==
Quantum chemistry computer programs
== References ==
== External links ==
Software for Chemistry & Materials | Wikipedia/Amsterdam_Density_Functional |
Monte Carlo molecular modelling is the application of Monte Carlo methods to molecular problems. These problems can also be modelled by the molecular dynamics method. The difference is that this approach relies on equilibrium statistical mechanics rather than molecular dynamics. Instead of trying to reproduce the dynamics of a system, it generates states according to appropriate Boltzmann distribution. Thus, it is the application of the Metropolis Monte Carlo simulation to molecular systems. It is therefore also a particular subset of the more
general Monte Carlo method in statistical physics.
It employs a Markov chain procedure in order to determine a new state for a system from a previous one. According to its stochastic nature, this new state is accepted at random. Each trial usually counts as
a move. The avoidance of dynamics restricts the method to studies of static quantities only, but the freedom to choose moves makes the method very flexible. These moves must only satisfy a basic condition of
balance in order for the equilibrium to be properly described, but detailed balance, a stronger condition,
is usually imposed when designing new algorithms. An additional advantage is that some systems, such as the Ising model, lack a dynamical description and are only defined by an energy prescription; for these the Monte Carlo approach is the only one feasible.
The great success of this method in statistical mechanics has led to various generalizations such as the method of simulated annealing for optimization, in which a fictitious temperature is introduced and then gradually lowered.
A range of software packages have been developed specifically for the use of the Metropolis Monte Carlo method on molecular simulations. These include:
BOSS
CP2K
MCPro
Sire
ProtoMS
Faunus
== See also ==
Quantum Monte Carlo
Monte Carlo method in statistical physics
List of software for Monte Carlo molecular modeling
Software for molecular mechanics modeling
Bond fluctuation model
== External links ==
https://web.archive.org/web/20220126175020/http://cmm.cit.nih.gov/intro_simulation/node25.html
== References ==
Allen, M.P. & Tildesley, D.J. (1987). Computer Simulation of Liquids. Oxford University Press. ISBN 0-19-855645-4.
Frenkel, D. & Smit, B. (2001). Understanding Molecular Simulation. Academic Press. ISBN 0-12-267351-4.
Binder, K. & Heermann, D.W. (2002). Monte Carlo Simulation in Statistical Physics. An Introduction (4th ed.). Springer. ISBN 3-540-43221-3. | Wikipedia/Monte_Carlo_molecular_modeling |
Materials Studio is software for simulating and modeling materials. It is developed and distributed by BIOVIA (formerly Accelrys), a firm specializing in research software for computational chemistry, bioinformatics, cheminformatics, molecular dynamics simulation, and quantum mechanics.
This software is used in advanced research of various materials, such as polymers, carbon nanotubes, catalysts, metals, ceramics, and so on, by universities (e.g., North Dakota State University), research centers, and high tech companies.
Materials Studio is a client–server model software package with Microsoft Windows-based PC clients and Windows and Linux-based servers running on PCs, Linux IA-64 workstations (including Silicon Graphics (SGI) Altix) and HP XC clusters.
== Software components ==
Analytical and Crystallization: to investigate, predict, and modify crystal structure and crystal growth.
Morphology
Polymorph Predictor
Reflex, Reflex Plus, Reflex QPA: to assist the interpretation of diffraction data for determination of crystallic structure, to validate the results of experiment and computation.
X-Cell: indexing for medium- to high-quality powder diffraction data from X-ray, neutron, and electron radiation sources.
Quantum and Catalysis
Adsorption Locator: to find the most stable adsorption sites for various materials, including zeolites, carbon nanotubes, silica gel, and activated carbon
CASTEP: to predict electronic, optical, and structural properties
ONETEP: to perform linear-scaling density functional theory simulations
DMol3: quantum mechanical methods to predict materials properties
Sorption: to predict fundamental properties, such as sorption isotherms (or loading curves) and Henry's constants
VAMP: high-speed calculation of a variety of physical and chemical molecular properties, e.g., for quick screening during drug discovery
QSAR, QSAR Plus: to identify compounds with optimal physicochemical properties.
Polymers and Classical Simulation: to construct and characterize models of isolated chains or bulk polymers and predict their properties
Materials Component Collection
Materials Visualizer
== Basic workflow ==
Materials Visualizer is used to construct/import graphical models of materials
Accurate structure is determined by quantum mechanical, semi-empirical, or classical simulation
Various required properties may be predicted/analyzed
== See also ==
Quantum chemistry computer programs
Comparison of software for molecular mechanics modeling
Molecular design software
List of software for Monte Carlo molecular modeling
List of software for nanostructures modeling
== References == | Wikipedia/Materials_Studio |
Cadmium nitrate describes any of the related members of a family of inorganic compounds with the general formula Cd(NO3)2·xH2O. The most commonly encountered form being the tetrahydrate.The anhydrous form is volatile, but the others are colourless crystalline solids that are deliquescent, tending to absorb enough moisture from the air to form an aqueous solution. Like other cadmium compounds, cadmium nitrate is known to be carcinogenic. According to X-ray crystallography, the tetrahydrate features octahedral Cd2+ centers bound to six oxygen ligands.
== Uses ==
Cadmium nitrate is used for coloring glass and porcelain and as a flash powder in photography.
== Preparation ==
Cadmium nitrate is prepared by dissolving cadmium metal or its oxide, hydroxide, or carbonate, in nitric acid followed by crystallization:
CdO + 2HNO3 → Cd(NO3)2 + H2O
CdCO3 + 2 HNO3 → Cd(NO3)2 + CO2 + H2O
Cd + 4HNO3 → 2NO2 + 2 H2O + Cd(NO3)2
== Reactions ==
Thermal dissociation at elevated temperatures produces cadmium oxide and oxides of nitrogen. When hydrogen sulfide is passed through an acidified solution of cadmium nitrate, yellow cadmium sulfide is formed. A red modification of the sulfide is formed under boiling conditions.
When treated with sodium hydroxide, solutions of cadmium nitrate yield a solid precipitate of cadmium hydroxide. Many insoluble cadmium salts are obtained by such precipitation reactions.
== References ==
== External links == | Wikipedia/Cadmium_nitrate |
Thorium(IV) nitrate is a chemical compound, a salt of thorium and nitric acid with the formula Th(NO3)4. A white solid in its anhydrous form, it can form tetra- and pentahydrates. As a salt of thorium it is weakly radioactive.
== Preparation ==
Thorium(IV) nitrate hydrate can be prepared by the reaction of thorium(IV) hydroxide and nitric acid:
Th(OH)4 + 4 HNO3 + 3 H2O → Th(NO3)4 + 5 H2O
Different hydrates are produced by crystallizing in different conditions. When a solution is very dilute, the nitrate is hydrolysed. Although various hydrates have been reported over the years, and some suppliers even claim to stock them,[1] only the tetrahydrate and pentahydrate actually exist. What is called a hexahydrate, crystallized from a neutral solution, is probably a basic salt.
The pentahydrate is the most common form. It is crystallized from dilute nitric acid solution.
The tetrahydrate, Th(NO3)4•4H2O is formed by crystallizing from a stronger nitric acid solution. Concentrations of nitric acid from 4 to 59% result in the tetrahydrate forming. The thorium atom has 12-coordination, with four bidentate nitrate groups and four water molecules attached to each thorium atom.
To obtain the anhydrous thorium(IV) nitrate, thermal decomposition of Th(NO3)4·2N2O5 is required. The decomposition occurs at 150-160 °C.
== Properties ==
Anhydrous thorium nitrate is a white substance. It is covalently bound with low melting point of 55 °C.
The pentahydrate Th(NO3)4•5H2O crystallizes with clear colourless crystals in the orthorhombic system. The unit cell size is a=11.191 b=22.889 c=10.579 Å. Each thorium atom is connected twice to each of four bidentate nitrate groups, and to three water molecules via their oxygen atoms. In total the thorium is eleven-coordinated. There are also two other water molecules in the crystal structure. The water is hydrogen bonded to other water, or to nitrate groups. The density is 2.80 g/cm3. Vapour pressure of the pentahydrate at 298K is 0.7 torr, and increases to 1.2 torr at 315K, and at 341K it is up to 10.7 torr. At 298.15K the heat capacity is about 114.92 calK−1mol−1. This heat capacity shrinks greatly at cryogenic temperatures. Entropy of formation of thorium nitrate pentahydrate at 298.15K is −547.0 calK−1mol−1. The standard Gibbs energy of formation is −556.1 kcalmol−1.
Thorium nitrate can dissolve in several different organic solvents including alcohols, ketones, esters and ethers. This can be used to separate different metals such as the lanthanides. With ammonium nitrate in the aqueous phase, thorium nitrate prefers the organic liquid, and the lanthanides stay with the water.
Thorium nitrate dissolved in water lowers it freezing point. The maximum freezing point depression is −37 °C with a concentration of 2.9 mol/kg.
At 25° a saturated solution of thorium nitrate contains 4.013 moles per liter. At this concentration the vapour pressure of water in the solution is 1745.2 Pascals, compared to 3167.2 Pa for pure water.
== Reactions ==
When thorium nitrate pentahydrate is heated, nitrates with less water are produced, however the compounds also lose some nitrate. At 140 °C a basic nitrate, ThO(NO3)2 is produced. When strongly heated thorium dioxide is produced.
A polymeric peroxynitrate is precipitated when hydrogen peroxide combines with thorium nitrate in solution with dilute nitric acid. Its formula is Th6(OO)10(NO3)4 •10H2O.
The hydrolysis of thorium nitrate solutions produces basic nitrates Th2(OH)4(NO3)4•xH2O and Th2(OH)2(NO3)6•8H2O. In crystals of Th2(OH)2(NO3).6•8H2O a pair of thorium atoms are connected by two bridging oxygen atoms. Each thorium atom is surrounded by three bidentate nitrate groups and three water molecules, bringing the coordination number to 11.
When oxalic acid is added to a thorium nitrate solution, insoluble thorium oxalate precipitates. Other organic acids added to thorium nitrate solution produce precipitates of organic salts with citric acid; basic salts, such as tartaric acid, adipic acid, malic acid, gluconic acid, phenylacetic acid, valeric acid. Other precipitates are also formed from sebacic acid and azelaic acid
== Double salts ==
Hexanitratothorates with the generic formula MI2Th(NO3)6 or MIITh(NO3)6•8H2O are made by mixing other metal nitrates with thorium nitrate in dilute nitric acid solution. MII can be Mg, Mn, Co, Ni, or Zn. MI can be Cs, (NO)+ or (NO2)+. Crystals the divalent metal thorium hexanitrate octahydrate have a monoclinic form with similar unit cell dimensions: β=97°, a=9.08 b=8.75-8 c=12.61-3.
Pentanitratothorates with the generic formula MITh(NO3)5•xH2O are known for MI being Na or K.
K3Th(NO3)7 and K3H3Th(NO3)10•4H2O are also known.
== Complexed salts ==
Thorium nitrate also crystallizes with other ligands and organic solvates including ethylene glycol diethyl ether, tri(n‐butyl)phosphate, butylamine, dimethylamine, and trimethylphosphine oxide.
== References ==
== Notes ==
1.^ Bogus hydrates include 12, 6, 5.5, 2 and 1 water molecules | Wikipedia/Thorium(IV)_nitrate |
Tin(IV) nitrate is a salt of tin with nitric acid. It is a volatile white solid, subliming at 40 °C under a vacuum. Unlike other nitrates, it reacts with water to produce nitrogen dioxide.
== Structure ==
It is structurally very similar to titanium(IV) nitrate, with the only major difference being the Sn–O bond(2.161 Å) being slightly longer than the Ti–O bond(2.068 Å).
== Production ==
It was first prepared in the 1960s. Tin(IV) chloride was added to dinitrogen pentoxide at -78 °C, which produced tin(IV) nitrate and nitryl chloride:
SnCl4 + 4 N2O5 → Sn(NO3)4 + 4 NO2Cl
Attempts to prepare this compound by reacting tin(II) oxide and nitric acid resulted in a formation of tin(II) nitrate hydroxide.
== Reactions ==
This compound is sensitive to water, it hydrolyzes into tin(IV) oxide and nitrogen dioxide.
Tin(IV) nitrate reacts with trifloroacetic acid anhydride to yield (NO2+)2[Sn(OOCCF3)62−] which is a nitronium salt. With trifluoroacetic acid a similar compound solvated with trifluoroacetic acid is produced.
It also reacts with acetic anhydride or acetic acid to produce tin(IV) acetate and with nitric oxide to produce tin(IV) oxynitrate.
The reaction of tin(IV) nitrate with triphenylphosphine and triphenylarsine yields dinitratotin(IV)bis(diphenylphosphonate) and dinitratotin(IV)bis(diphenylarsonate).
== References == | Wikipedia/Tin(IV)_nitrate |
An oxalate nitrate is a chemical compound or salt that contains oxalate and nitrate anions (NO3− and C2O42-). These are mixed anion compounds. Some have third anions. Oxalate acts as a ligand, which normally complexes two metal atoms.
== Naming ==
An oxalate nitrate compound may also be called a nitrate oxalate. In chemical formulae, oxalate may be indicated by "ox". As a ligand oxalate is termed "oxalato", and nitrate, "nitrato".
== Production ==
Most oxalate nitrates are formed by crystallisation from water solutions. One issue is the insolubility of metal oxalates.
== Properties ==
On heating, oxalate nitrates lose NO2, NO, CO, and CO2 and form metal carbonates or oxides.
== Related ==
Related to these are the oxalate phosphates and oxalate perchlorates.
== List ==
== References == | Wikipedia/Oxalate_nitrate |
Isosorbide dinitrate is a medication used for heart failure, esophageal spasms, and to treat and prevent angina pectoris. It has been found to be particularly useful in heart failure due to systolic dysfunction together with hydralazine. It is taken by mouth or under the tongue.
Common side effects include headache, lightheadedness with standing, and blurred vision. Severe side effects include low blood pressure. It is unclear if use in pregnancy is safe for the baby. It should not be used together with PDE5 Inhibitors. Isosorbide dinitrate is in the nitrate family of medications and works by dilating blood vessels.
Isosorbide dinitrate was first written about in 1939. It is on the World Health Organization's List of Essential Medicines. Isosorbide dinitrate is available as a generic medication. A long-acting form exists. In 2022, isosorbide was the 119th most commonly prescribed medication in the United States, with more than 5 million prescriptions.
== Medical uses ==
It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms. It is available as an oral tablet both in extended release and slow release. The onset of action for Isosorbide Dinitrate is thirty minutes and the onset of action for oral extended release is 12–24 hours.
Long-acting nitrates can be more useful as they are generally more effective and stable in the short term.
== Side effects ==
=== Tolerance ===
After long-term use for treating chronic conditions, tolerance may develop in patients, reducing its effectiveness. The mechanisms of nitrate tolerance have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. These include:
Impaired biotransformation of isosorbide dinitrate to its active principle NO (or a NO-related species)
Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by isosorbide dinitrate
Plasma volume expansion
The oxidative stress hypothesis
The last hypothesis might represent a unifying hypothesis, and an isosorbide dinitrate-induced inappropriate production of oxygen free radicals might induce a number of abnormalities which include the ones described above.
Furthermore, nitrate tolerance is shown to be associated with vascular abnormalities which have the potential to worsen patients prognosis: these include endothelial and autonomic dysfunction.
== Mechanism of action ==
Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent sequestration of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.
== Society and culture ==
Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by Schwarz and Isordil by Valeant, according to FDA Orange Book. It is sold under the trade name Isoket in the United Kingdom, Argentina, and Hong Kong. It is also a component of BiDil.
== References == | Wikipedia/Isosorbide_dinitrate |
Terbium(III) nitrate is an inorganic chemical compound, a salt of terbium and nitric acid, with the formula Tb(NO3)3. The hexahydrate crystallizes as triclinic colorless crystals with the formula [Tb(NO3)3(H2O)4]·2H2O. It can be used to synthesize materials with green emission.
== Preparation ==
Terbium(III) nitrate can be prepared by dissolving terbium(III,IV) oxide in a mixture of aqueous HNO3 and H2O2 solution.
Terbium(III) nitrate can be obtained by reacting terbium(III) oxide with nitric acid and crystallizing then drying the crystals with 45~55% sulfuric acid to obtain the hexahydrate.
== Properties ==
It reacts with NH4HCO3 to produce Tb2(CO3)3 along with its basic carbonate. It forms Tb(NO3)2−5 in CH3CN with excess nitrate anions.
== References == | Wikipedia/Terbium(III)_nitrate |
Barium nitrate is the inorganic compound with the chemical formula Ba(NO3)2. It, like most barium salts, is colorless, toxic, and water-soluble. It burns with a green flame and is an oxidizer; the compound is commonly used in pyrotechnics.
== Manufacture, occurrence, and reactions ==
Barium nitrate is manufactured by two processes that start with the main source material for barium, the carbonate. The first involves dissolving barium carbonate in nitric acid, allowing any iron impurities to precipitate, then filtered, evaporated, and crystallized. The second requires combining barium sulfide with nitric acid.
It occurs naturally as the very rare mineral nitrobarite.
At elevated temperatures, barium nitrate decomposes to barium oxide:
2 Ba(NO3)2 → 2 BaO + 4 NO2 + O2
== Applications ==
Barium nitrate is used in the production of BaO-containing materials.
=== Military ===
Although no longer produced, Baratol is an explosive composed of barium nitrate, TNT and binder; the high density of barium nitrate results in baratol being quite dense as well. Barium nitrate mixed with aluminium powder, a formula for flash powder, is highly explosive. It is mixed with thermite to form Thermate-TH3, used in military thermite grenades. Barium nitrate was also a primary ingredient in the "SR 365" incendiary charge used by the British in the De Wilde incendiary ammunition with which they armed their interceptor fighters, such as the Hawker Hurricane and Supermarine Spitfire, during the Battle of Britain. It is also used in the manufacturing process of barium oxide, the vacuum tube industry and for green fire in pyrotechnics.
== Safety ==
Like all soluble barium compounds, barium nitrate is toxic by ingestion or inhalation.
Solutions of sulfate salts such as Epsom salts or sodium sulfate may be given as first aid for barium poisoning, as they precipitate the barium as the insoluble (and non-toxic) barium sulfate.
Inhalation may also cause irritation to the respiratory tract.
While skin or eye contact is less harmful than ingestion or inhalation, it can still result in irritation, itching, redness, and pain.
The Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health have set occupational exposure limits at 0.5 mg/m3 over an eight-hour time-weighted average.
== References == | Wikipedia/Barium_nitrate |
Manganese(II) nitrate refers to the inorganic compounds with formula Mn(NO3)2·(H2O)n. These compounds are nitrate salts containing varying amounts of water. A common derivative is the tetrahydrate, Mn(NO3)2·4H2O, but mono- and hexahydrates are also known as well as the anhydrous compound. Some of these compounds are useful precursors to the oxides of manganese. Typical of a manganese(II) compound, it is a paramagnetic pale pink solid.
== Structure ==
Manganese(II) compounds, especially with oxygenated ligands, are typically octahedral. Following this trend, the tetrahydrate features four aquo ligands bound to Mn as well as two mutually cis, unidentate nitrate ligands. The hexaaquo salt features octahedral [Mn(H2O)6]2+.
== Preparation, reactions, uses ==
Manganese(II) nitrate is prepared from manganese dioxide and nitrogen dioxide:
MnO2 + 2 NO2 + 4 H2O → Mn(H2O)4(NO3)2
In this redox reaction, two moles of the reductant NO2 (gas) donate each one electron to MnO2 (black solid), the oxidant, which is reduced from its oxidation state (+4) to its lower state (+2). Simultaneously, NO2 (+4) is oxidized to form nitrate (NO−3) (+5).
Heating the tetrahydrate to 110 °C gives the pale yellow monohydrate.
The reaction is reversible in the sense that heating the Mn(II) dinitrate to 450 °C gives a slightly nonstoichiometric Mn(IV) dioxide.
Manganese(II) nitrate is the precursor to manganese(II) carbonate (MnCO3), which is used in fertilizers and as a colourant. The advantage of this method, based on the use of ammonia (NH3) and carbon dioxide (CO2) as reaction intermediates, being that the side product ammonium nitrate (NH4NO3) is also useful as a fertilizer.
== References == | Wikipedia/Manganese(II)_nitrate |
Thallium(III) nitrate, also known as thallic nitrate, is a thallium compound with chemical formula Tl(NO3)3. Normally found as the trihydrate, it is a colorless and highly toxic salt which hydrolyses in water to thallium(III) oxide. It is a strong oxidizing agent useful in organic synthesis.
== Prepration ==
The trihydrate is prepared by dissolving thallium(III) oxide in concentrated nitric acid at 80 °C, followed by cooling of the resulting solution:
Tl2O3 + 6 HNO3 → 2 Tl(NO3)3 + 3 H2O
== Structure ==
Thallium(III) nitrate trihydrate, Tl(NO3)3·3H2O, crystallizes in the hexagonal crystal system and consists of a nine-coordinate thallium center with three bidentate nitrate ligands and three monodentate water ligands.
== Organic synthesis ==
Despite its toxicity, thallium(III) nitrate is sometimes used in the laboratory, such as in the oxidation of methoxyl phenols to quinone acetals:
Another use of thallium(III) nitrate is the oxidization of alkenes to acetals, cyclic alkenes to ring contracted aldehydes, and terminal alkynes to carboxylic acids. Ketones are also oxidized to carboxylic acids or esters in the presence of methanol. Illustrated below is an example of alkene oxidation to an acetal:
== References == | Wikipedia/Thallium(III)_nitrate |
Aluminium nitrate is a white, water-soluble salt of aluminium and nitric acid, most commonly existing as the crystalline hydrate, aluminium nitrate nonahydrate, Al(NO3)3·9H2O.
== Preparation ==
Aluminium nitrate cannot be synthesized by the reaction of aluminium with concentrated nitric acid, as the aluminium forms a passivation layer.
Aluminium nitrate may instead be prepared by the reaction of nitric acid with aluminium(III) chloride. Nitrosyl chloride is produced as a by-product; it bubbles out of the solution as a gas. More conveniently, the salt can be made by reacting nitric acid with aluminium hydroxide.
Aluminium nitrate may also be prepared a metathesis reaction between aluminium sulfate and a nitrate salt with a suitable cation such as barium, strontium, calcium, silver, or lead. e.g. Al2(SO4)3 + 3 Ba(NO3)2 → 2 Al(NO3)3 + 3 BaSO4.
== Uses ==
Aluminium nitrate is a strong oxidizing agent. It is used in tanning leather, antiperspirants, corrosion inhibitors, extraction of uranium, petroleum refining, and as a nitrating agent.
The nonahydrate and other hydrated aluminium nitrates have many applications. These salts are used to produce alumina for preparation of insulating papers, in cathode ray tube heating elements, and on transformer core laminates. The hydrated salts are also used for the extraction of actinide elements.
It is used in the laboratory and classroom such as in the reaction
Al(NO3)3 + 3 NaOH → Al(OH)3 + 3 NaNO3
It is, however, much less often encountered than aluminium chloride and aluminium sulfate.
== References ==
== External links ==
MSDS of nonahydrate
Government of Canada Fact Sheets and Frequently Asked Questions: Aluminum Salts | Wikipedia/Aluminium_nitrate |
Holmium (III) nitrate is an inorganic compound, a salt of holmium and nitric acid with the chemical formula Ho(NO3)3. The compound forms yellowish crystals, dissolves in water, also forms crystalline hydrates.
== Synthesis ==
Anhydrous salt is obtained by the action of nitrogen dioxide on holmium(III) oxide:
2
H
o
2
O
3
+
9
N
2
O
4
→
150
o
C
4
H
o
(
N
O
3
)
3
+
6
N
O
{\displaystyle {\mathsf {2Ho_{2}O_{3}+9N_{2}O_{4}\ {\xrightarrow {150^{o}C}}\ 4Ho(NO_{3})_{3}+6NO}}}
Effect of nitrogen dioxide on metallic holmium:
H
o
+
3
N
2
O
4
→
200
o
C
H
o
(
N
O
3
)
3
+
3
N
O
{\displaystyle {\mathsf {Ho+3N_{2}O_{4}\ {\xrightarrow {200^{o}C}}\ Ho(NO_{3})_{3}+3NO}}}
Reaction of holmium hydroxide and nitric acid:
H
o
(
O
H
)
3
+
3
N
H
O
3
→
150
o
C
H
o
(
N
O
3
)
3
+
3
H
2
O
{\displaystyle {\mathsf {Ho(OH)_{3}+3NHO_{3}\ \xrightarrow {150^{o}C} \ Ho(NO_{3})_{3}+3H_{2}O}}}
== Physical properties ==
Holmium(III) nitrate forms yellowish crystals.
Forms a crystalline hydrate of the composition Ho(NO3)3•5H2O.
Soluble in water and ethanol.
== Chemical properties ==
Hydrated holmitic nitrate thermally decomposes to form HoONO3 and decomposes to holmium oxide upon subsequent heating.
== Application ==
The compound is used for the production of ceramics and glass.
Also used to produce metallic holmium and as a chemical reagent.
== References == | Wikipedia/Holmium(III)_nitrate |
Samarium(III) nitrate is an odorless, white-colored chemical compound with the formula Sm(NO3)3. It forms the hexahydrate, which decomposes at 50°C to the anhydrous form. When further heated to 420°C, it is converted to the oxynitrate, and at 680°C it decomposes to form samarium(III) oxide.
== Synthesis ==
Samarium(III) nitrate is produced by the reaction of samarium hydroxide and nitric acid:
Sm(OH)3 + 3HNO3 → Sm(NO3)3 + 3H2O
== Uses ==
Samarium(III) nitrate is a lewis acid catalyst that is used to produce a nitrate precursor solution that is used as a nanocatalyst in the solid oxide regenerative fuel cells. The nanocatalyst is made by mixing samarium(III) nitrate hexahydrate, strontium nitrate, and cobalt(II) nitrate hexahydrate.
Samarium(III) nitrate is also used for the preparation of samarium doped ceria, which can be used in the fabrication of electrolytes for fuel cells. The samarium doped ceria is produced by mixing cerium(III) nitrate and samarium(III) nitrate together using triethylene glycol as a solvent for 5 hours at 200°C. Then it was dried for 4 hours at 110°C which resulted in a brown solid. Then it was heated up to 500°C for two hours which made the samarium doped ceria.
== References == | Wikipedia/Samarium(III)_nitrate |
Iron(III) nitrate, or ferric nitrate, is the name used for a series of inorganic compounds with the formula Fe(NO3)3.(H2O)n. Most common is the nonahydrate Fe(NO3)3.(H2O)9. The hydrates are all pale colored, water-soluble paramagnetic salts.
== Hydrates ==
Iron(III) nitrate is deliquescent, and it is commonly found as the nonahydrate Fe(NO3)3·9H2O, which forms colourless to pale violet crystals. This compound is the trinitrate salt of the aquo complex [Fe(H2O)6]3+.
Other hydrates Fe(NO3)3·xH2O, include:
tetrahydrate (x=4), more precisely triaqua dinitratoiron(III) nitrate monohydrate, [Fe(NO3)2(H2O)3]NO3·H2O, has complex cations wherein Fe3+ is coordinated with two nitrate anions as bidentate ligands and three of the four water molecules, in a pentagonal bipyramid configuration with two water molecules at the poles.
pentahydrate (x=5), more precisely penta-aqua nitratoiron(III) dinitrate, [Fe(NO3)(H2O)5](NO3)2, in which the Fe3+ ion is coordinated to five water molecules and a unidentate nitrate anion ligand in octahedral configuration.
hexahydrate (x=6), more precisely hexaaquairon(III) trinitrate, [Fe(H2O)6](NO3)3, where the Fe3+ ion is coordinated to six water molecules in octahedral configuration.
== Reactions ==
Iron(III) nitrate is a useful precursor to other iron compounds because the nitrate is easily removed or decomposed. It is for example, a standard precursor to potassium ferrate K2FeO4.
When dissolved, iron(III) nitrate forms yellow solutions. When this solution is heated to near boiling, nitric acid evaporates and a solid precipitate of iron(III) oxide Fe2O3 appears. Another method for producing iron oxides from this nitrate salt involves neutralizing its aqueous solutions.
== Preparation ==
The compound can be prepared by treating iron metal powder with nitric acid, as summarized by the following idealized equation:
Fe + 4 HNO3 + 7 H2O → Fe(NO3)3(H2O)9 + NO
== Applications ==
Ferric nitrate has no large scale applications. It is a catalyst for the synthesis of sodium amide from a solution of sodium in ammonia:
2 NH3 + 2Na → 2 NaNH2 + H2
Certain clays impregnated with ferric nitrate have been shown to be useful oxidants in organic synthesis. For example, ferric nitrate on Montmorillonite—a reagent called Clayfen—has been employed for the oxidation of alcohols to aldehydes and thiols to disulfides.
Ferric nitrate solutions are used by jewelers and metalsmiths to etch silver and silver alloys.
== References == | Wikipedia/Iron(III)_nitrate |
Rubidium nitrate is an inorganic compound with the formula RbNO3. This alkali metal nitrate salt is white and highly soluble in water.
== Properties ==
Rubidium nitrate is a white crystalline powder that is highly soluble in water and very slightly soluble in acetone. In a flame test, RbNO3 gives a mauve/light purple colour.
== Uses ==
Rubidium compounds have very few applications. Like caesium nitrate, it is used in infrared radiation optics, in pyrotechnic compositions as a pyrotechnic colorant and as an oxidizer, e.g. in decoys and illumination flares although it is rarely used in fireworks to produce a red-violet colour. It is also used as a raw material for preparation of other rubidium compounds and rubidium metal, for manufacture of catalysts and in scintillation counters.
== Production ==
RbNO3 can be prepared either by dissolving rubidium metal, its hydroxide or carbonate in nitric acid.
RbOH + HNO3 → RbNO3 + H2O
Rb2CO3 + 2 HNO3 → 2 RbNO3 + CO2 + H2O
2 Rb + 2 HNO3 → 2 RbNO3 + H2
== References == | Wikipedia/Rubidium_nitrate |
Indium(III) nitrate is a nitrate salt of indium which forms various hydrates. Only the pentahydrate has been crystallographically verified. Other hydrates are also reported in literature, such as the trihydrate.
== Production and reactions ==
Indium(III) nitrate hydrate is produced by the dissolution of indium metal in concentrated nitric acid followed by evaporation of the solution:
In + 4 HNO3 → In(NO3)3 + NO + 2 H2O
The hydrate first decomposes to a basic salt and then to indium(III) oxide at 240 °C. Anhydrous indium(III) nitrate is claimed to be produced by the reaction of anhydrous indium(III) chloride and dinitrogen pentoxide.
In the presence of excess nitrate ions, indium(III) nitrate converts to the [In(NO3)4]− ion.
The hydrolysis of indium(III) nitrate yields indium(III) hydroxide. It also reacts with sodium tungstate to form In(OH)WO4, [In(OH)2]2WO4, NaInWO4 or In2(WO4)3 depending on pH.
== Structure ==
Only the pentahydrate has been structurally elucidated. The pentahydrate consists of octahedral [In(NO3)(H2O)5]2+ centers as well as two nitrates and is monoclinic.
== References == | Wikipedia/Indium(III)_nitrate |
Caesium nitrate or cesium nitrate is a salt with the chemical formula CsNO3. An alkali metal nitrate, it is used in pyrotechnic compositions, as a colorant and an oxidizer, e.g. in decoys and illumination flares. The caesium emissions are chiefly due to two powerful spectral lines at 852.113 nm and 894.347 nm.
Caesium nitrate prisms are used in infrared spectroscopy, in x-ray phosphors, and in scintillation counters. It is also used in making optical glasses and lenses.
As with other alkali metal nitrates, caesium nitrate decomposes on gentle heating to give caesium nitrite:
2 CsNO3 → 2 CsNO2 + O2
Caesium also forms two unusual acid nitrates, which can be described as CsNO3·HNO3 and CsNO3·2HNO3 (melting points 100 °C and 36–38 °C respectively).
== References == | Wikipedia/Caesium_nitrate |
Palladium(II) nitrate is the inorganic compound with the formula Pd(NO3)2.(H2O)x where x = 0 or 2. The anhydrous and dihydrate are deliquescent solids. According to X-ray crystallography, both compounds feature square planar Pd(II) with unidentate nitrate ligands. The anhydrous compound, which is a coordination polymer, is yellow.
As a solution in nitric acid, Pd(NO3)2 catalyzes the conversion of alkenes to dinitrate esters. Its pyrolysis affords palladium oxide.
== Preparation ==
Hydrated palladium nitrate may be prepared by dissolving palladium oxide hydrate in dilute nitric acid followed by crystallization. The nitrate crystallizes as yellow-brown deliquescent prisms. The anhydrous material is obtained by treating palladium metal with fuming nitric acid.
== References == | Wikipedia/Palladium(II)_nitrate |
Isosorbide mononitrate, sold under many brand names, is a medication used for heart-related chest pain (angina), heart failure and esophageal spasms. It can be used both to treat and to prevent heart-related chest pain; however, it is generally less preferred than beta blockers or calcium channel blockers. It is taken by mouth.
Common side effects include headache, low blood pressure with standing, blurry vision, and skin flushing. Serious side effects may include low blood pressure especially if also exposed to PDE5 inhibitors such as sildenafil. Use is not recommended in pregnancy. It is believed to work by relaxing smooth muscle within blood vessels.
It was patented in 1971 and approved for medical use in 1981. It is available as a generic medication. In 2022, isosorbide was the 119th most commonly prescribed medication in the United States, with more than 5 million prescriptions.
== Medical uses ==
Isosorbide mononitrate is a nitrate-class drug used for the prevention of angina pectoris. The sublingual patch has an onset of five minutes and a duration of action of one hour. The oral, slow release tablet has an onset of thirty minutes, and a duration of 8 hours.
== Adverse effects ==
The following adverse effects have been reported in studies with isosorbide mononitrate:
Very common: Headache predominates (up to 30%) necessitating withdrawal of 2 to 3% of patients, but the incidence reduces rapidly as treatment continues.
Common: Tiredness, sleep disturbances (6%) and gastrointestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate modified-release tablets, but at a frequency no greater than for placebo. Hypotension (4 to 5%), poor appetite (2.5%), nausea (1%)
Adverse effects associated with the clinical use of the drug are as expected with all nitrate preparations. They occur mainly in the early stages of treatment.
Hypotension (4%) with symptoms such as dizziness and nausea (1%) have been reported. In general, these symptoms disappear during long-term treatment.
Other reactions that have been reported with isosorbide mononitrate-modified release tablets include tachycardia, vomiting, diarrhoea, vertigo, and heartburn.
== Interactions ==
Sildenafil (Viagra). Concomitant administration of isosorbide mononitrate and sildenafil (Viagra) or other phosphodiesterase inhibitors (Tadalafil and Udenafil) can potentiate the vasodilatory effect of isosorbide mononitrate with the potential result of serious side-effects such as syncope or myocardial infarction. Life-threatening hypotension may also occur. Therefore, sildenafil should not be given to patients already receiving isosorbide mononitrate therapy.
Sulfhydryl-containing compounds. The metabolism of organic nitrates to nitric oxide is dependent on the presence of sulfhydryl groups in the muscle. The combination of oral N-acetylcysteine and a single dose of sustained-release isosorbide mononitrate 60 mg significantly prolonged the total exercise time in patients with angina pectoris and angiographically proven significant coronary artery disease, when compared with isosorbide mononitrate alone. Concomitant administration of other exogenous sources of sulfhydryl groups such as methionine and captopril may produce a similar interaction.
Phenylalkylamine calcium antagonists. The addition of a calcium channel blocker of the verapamil type, such as gallopamil 75 mg, has been shown to further improve left ventricular functional parameters when given in combination with isosorbide mononitrate in a sustained-release formulation.
Propranolol. The addition of isosorbide mononitrate to propranolol treatment in patients with cirrhosis and portal hypertension caused a marked fall in portal pressure, a reduction in hepatic blood flow, cardiac output and mean arterial blood pressure, but no additional change in azygos blood flow. The additional effect of isosorbide mononitrate was especially evident in patients whose portal pressure was not reduced by propranolol.
Calcium antagonists (general). Marked symptomatic orthostatic hypotension has been reported when calcium antagonists and organic nitrates were used in combination. Dose adjustments of either class of agent may be necessary.
== Brand names ==
It is sold in the US by Lannett Company, under the brand name Monoket, and was also sold in the US under the name Imdur, and marketed in the UK under the trade names: Isotard, Monosorb, Chemydur. In India, this drug is available under the brand names of Ismo, Imdur, Isonorm, Monotrate, Solotrate, and Monit. In Russia it is occasionally used under the brand names Monocinque and Pektrol. In Australia, this drug is available under the brand name Duride.
== References == | Wikipedia/Isosorbide_mononitrate |
Xenon nitrate, also called xenon dinitrate, is an inorganic compound consisting of one xenon atom bonded to two nitrate groups. It can be made by reacting xenon difluoride with anhydrous nitric acid, but it only exists transiently before decomposing, and therefore it has not been isolated and fully characterized. A related compound, xenon fluoride nitrate, has been made and is stable enough to be studied in more detail.
== Production ==
Attempted production has used the following reaction:
XeF2 + 2 HNO3 → Xe(NO3)2 + 2 HF
This reaction makes a red-brown solid. However, it decomposes spontaneously at 23 °C, turning blue temporarily while doing so:
Xe(NO3)2 → Xe + O2NOONO2 (an unstable nitrogen peroxide)
== References == | Wikipedia/Xenon_nitrate |
Iron(II) nitrate is the nitrate salt of iron(II). It is commonly encountered as the green hexahydrate, Fe(NO3)2·6H2O, which is a metal aquo complex, however it is not commercially available unlike iron(III) nitrate due to its instability to air. The salt is soluble in water and serves as a ready source of ferrous ions.
== Structure ==
No structure of any salt Fe(NO3)2·xH2O has been determined by X-ray crystallography. Nonetheless, the nature of the aquo complex [Fe(H2O)6]2+ is well known and relatively insensitive to the anion. The Fe-O distances are longer for [Fe(H2O)6]2+ (2.13 Å) than for the ferric analogue [Fe(H2O)6]3+ (1.99 Å). Both [Fe(H2O)6]n+ complexes are high spin, which results in pale colors, paramagnetism, and weak Fe-O bonds.
== Production ==
Iron(II) nitrate can be produced in multiple ways, such as the reaction of iron metal with cold dilute nitric acid:
3 Fe + 8 HNO3 + 12 H2O → 3 Fe(NO3)2(H2O)6 + 2 NO
If this reaction is conducted below -10 °C, nonahydrate is produced. It readily releases water to give the hexahydrate.
The above reaction can also co-produce ferric nitrate. Reacting iron(II) sulfate and lead nitrate under dilute ethanol and then evaporating the solution leads to the formation of the green crystals of the hexahydrate. A solution of iron(II) nitrate is produced by the ion-exchange reaction of iron(II) sulfate and barium nitrate, producing a concentration of up to 1.5 M due to the limited solubility of barium nitrate.
The solution of the iron(II) nitrate-hydrazine complex is produced by the reaction of hydrazine nitrate and ferric nitrate at 40 °C with copper(II) nitrate as a catalyst:
4 Fe(NO3)3 + N2H5NO3 → 4 Fe(NO3)2 + N2 + 4 HNO3
If the compound is used in situ, the compound is produced by the reaction of iron(II) chloride and calcium nitrate:
FeCl2 + Ca(NO3)2 → Fe(NO3)2 + CaCl2
== Reactions ==
The hexahydrate melts at 60 °C and then decomposes at 61 °C into iron(III) oxide rather than iron(II) oxide. A solution of iron(II) nitrate is much more stable, decomposing at 107 °C to iron(III), with the presence of nitric acid lowering the decomposition temperature. Concentrated nitric acid oxidizes iron(II) nitrate into iron(III) nitrate:
3 Fe(NO3)2 + 4 HNO3 → 3 Fe(NO3)3 + NO + 2 H2O
== Uses ==
Iron(II) nitrate has no uses, however, there is a potential use for dye removal.
== References == | Wikipedia/Iron(II)_nitrate |
Mercury(II) nitrate is an inorganic compound with the chemical formula Hg(NO3)2. It is the mercury(II) salt of nitric acid HNO3. It contains mercury(II) cations Hg2+ and nitrate anions NO−3, and water of crystallization H2O in the case of a hydrous salt. Mercury(II) nitrate forms hydrates Hg(NO3)2·xH2O. Anhydrous and hydrous salts are colorless or white soluble crystalline solids that are occasionally used as a reagents. Mercury(II) nitrate is made by treating mercury with hot concentrated nitric acid. Neither anhydrous nor monohydrate has been confirmed by X-ray crystallography. The anhydrous material is more widely used.
== Uses ==
Mercury(II) nitrate is used as an oxidizing agent in organic synthesis, as a nitrification agent, as an analytical reagent in laboratories, in the manufacture of felt, and in the manufacture of mercury fulminate.
An alternative qualitative Zeisel test can be done with the use of mercury(II) nitrate instead of silver nitrate, leading to the formation of scarlet red mercury(II) iodide.
== Health information ==
Mercury compounds are highly toxic. The use of this compound by hatters and the subsequent mercury poisoning of said hatters is a common theory of where the phrase "mad as a hatter" came from.
== See also ==
Mercury
The Hatter
Mercury poisoning
Gilding
== References ==
== External links ==
ATSDR - Toxic Substances Portal - Mercury (11/14/2013)
ATSDR - Public Health Statement: Mercury (11/14/2013)
ATSDR - ALERT! Patterns of Metallic Mercury Exposure, 6/26/97 (link not traceable 11/14/2013)
ATSDR - Medical Management Guidelines for Mercury (11/14/2013)
ATSDR - Toxicological Profile: Mercury (11/14/2013)
Safety data (MSDS) (link not traceable 11/14/2013)
Mercuric Nitrate (ICSC)
Mercury Archived 2018-02-17 at the Wayback Machine
Mercury Information Packages
How to Make Good Mercury Electrical Connections, Popular Science monthly, February 1919, Unnumbered page, Scanned by Google Books: https://books.google.com/books?id=7igDAAAAMBAJ&pg=PT14 | Wikipedia/Mercury(II)_nitrate |
Ullmann's Encyclopedia of Industrial Chemistry is a major reference work related to industrial chemistry by chemist Fritz Ullmann, first published in 1914, and exclusively in German as "Enzyklopädie der Technischen Chemie" until 1984.
== History ==
Ullmann's Encyclopedia of Industrial Chemistry is a major reference work related to industrial chemistry by chemist Fritz Ullmann. Its first edition was published in German by Fritz Ullmann in 1914. The fourth edition, published 1972 to 1984, already contained 25 volumes. The fifth edition, published 1985 to 1996, was the first version available in English. In 1997, the first online version was published. The year 2014 marked its centenary.
As of 2016, Ullmann's Encyclopedia was in its seventh edition, in 40 volumes, including one index volume and more than 1,050 articles (200 more than the sixth edition), approximately 30,000 pages, 22,000 images, 8,000 tables, 19,000 references and 85,000 indices.
== Editions ==
1914–1922: 1st edition in 12 volumes, which can be viewed online (hosted by Internet Archive)
1928–1932: 2nd edition in 11 volumes
1951–1970: 3rd edition in 22 volumes, of which volume 2 is in two sub-volumes
1972–1984: 4th edition in 25 volumes, last edition in German language
1985–1996: 5th edition, in English only, titled Ullmann's Encyclopedia of Industrial Chemistry, in 36 volumes
2002–2007: 6th edition in 40 volumes
2011–2014: 7th edition in 40 print volumes, with ongoing changes and additions to the online edition
== Editors and contributors ==
Barbara Elvers (Wiley-VCH) is currently Senior Editorial Advisor and Claudia Ley is Editor-in-Chief, both Wiley-VCH. The Editorial Board has around 20 members from different nations.
The encyclopedia is a multi-author work. Around 3,000 international authors from universities and industry contributed to it.
== Topics ==
Note: The "topics" are a selection of related articles provided by Wiley Online Library. The number (#) indicates that, for example, 15 articles relate to the main branch of agrochemicals. The numbers do not exactly sum up to the total number of articles (1,050), but its sole purpose is for organizing and categorizing the large number of articles where possible.
Agrochemicals (15 articles)
Analytical Techniques (30)
Biochemistry & Biotechnology (26)
Chemical Reactions (12)
Dyes and Pigments (29)
Energy (22)
Environmental Protection and Industrial Safety (29)
Fat, Oil, Food and Feed, Cosmetics (39)
Inorganic Chemicals (71)
Materials (33)
Metals and Alloys (38)
Organic Chemicals (114)
Pharmaceuticals (77)
Polymers and Plastics (57)
Processes & Process Engineering (86)
Renewable Resources (20)
Special Topics (64)
== Kirk-Othmer Encyclopedia of Chemical Technology ==
In the 1940s, American Chemists Donald F. Othmer and Raymond E. Kirk from New York University began to create an English counterpart to Ullmann, named the Kirk-Othmer Encyclopedia of Chemical Technology. It was originally published by Wiley, which in 1996 took over the German Wiley-VCH publishing house and thus has combined the two encyclopedias ever since. The German chemistry magazine CHEManager wrote, quote: "In a double pack, the two companion works are simply unbeatable, because the knowledge gathered in both offers answers (almost) all questions that can arise in connection with chemical products and processes". These two encyclopedias were compared in Reference Reviews in 2007.
As of 2004, Kirk-Othmer was in its 5th edition with more than 1,300 articles in 27 volumes with over 22,950 pages.
== External links ==
Ullmann's Encyclopedia of Industrial Chemistry, 7th edition online – continuously updated (English)
Ullmann's Encyclopedia of Industrial Chemistry, 7th edition print version
Kirk-Othmer Encyclopedia of Chemical Technology, 5th edition online – continuously updated (English)
Kirk-Othmer Encyclopedia of Chemical Technology, 5.th edition print version
== References == | Wikipedia/Ullmann's_Encyclopedia_of_Industrial_Chemistry |
Magnesium nitrate refers to inorganic compounds with the formula Mg(NO3)2(H2O)x, where x = 6, 2, and 0. All are white solids. The anhydrous material is hygroscopic, quickly forming the hexahydrate upon standing in air. All of the salts are very soluble in both water and ethanol.
== Occurrence, preparation, structure ==
Being highly water-soluble, magnesium nitrate occurs naturally only in mines and caverns as nitromagnesite (hexahydrate form).
The magnesium nitrate used in commerce is made by the reaction of nitric acid and various magnesium salts.
== Use ==
The principal use is as a dehydrating agent in the preparation of concentrated nitric acid.
Its fertilizer grade has 10.5% nitrogen and 9.4% magnesium, so it is listed as 10.5-0-0 + 9.4% Mg. Fertilizer blends containing magnesium nitrate also have ammonium nitrate, calcium nitrate, potassium nitrate and micronutrients in most cases; these blends are used in the greenhouse and hydroponics trade.
== Reactions ==
Magnesium nitrate reacts with alkali metal hydroxide to form the corresponding nitrate:
Mg(NO3)2 + 2 NaOH → Mg(OH)2 + 2 NaNO3.
Since magnesium nitrate has a high affinity for water, heating the hexahydrate does not result in the dehydration of the salt, but rather its decomposition into magnesium oxide, oxygen, and nitrogen oxides:
2 Mg(NO3)2 → 2 MgO + 4 NO2 + O2.
The absorption of these nitrogen oxides in water is one possible route to synthesize nitric acid. Although inefficient, this method does not require the use of any strong acid.
It is also occasionally used as a desiccant.
== References ==
Liquid Chemistry
Nitromagnesite Mineral Data
Magnesium Nitrate MSDS | Wikipedia/Magnesium_nitrate |
The sulfate nitrates are a family of double salts that contain both sulfate and nitrate ions (NO3−, SO42−). They are in the class of mixed anion compounds. A few rare minerals are in this class. Two sulfate nitrates are in the class of anthropogenic compounds, accidentally made as a result of human activities in fertilizers that are a mix of ammonium nitrate and ammonium sulfate, and also in the atmosphere as polluting ammonia, nitrogen dioxide, and sulfur dioxide react with the oxygen and water there to form solid particles. The nitro group (NO3−) can act as a ligand, and complexes containing it can form salts with sulfate.
== List ==
== References == | Wikipedia/Sulfate_nitrates |
Nitroglycerin, also known as glyceryl trinitrate (GTN), is a vasodilator used for heart failure, high blood pressure, anal fissures, painful periods, and to treat and prevent chest pain caused by decreased blood flow to the heart (angina) or due to the recreational use of cocaine. This includes chest pain from a heart attack. It is taken by mouth, under the tongue, applied to the skin, or by injection into a vein.
Common side effects include headache and low blood pressure. The low blood pressure can be severe. It is unclear if use in pregnancy is safe for the fetus. It should not be used together with medications within the PDE5 inhibitor family such as sildenafil due to the risk of low blood pressure. Nitroglycerin is in the nitrate family of medications. While it is not entirely clear how it works, it is believed to function by dilating blood vessels.
Nitroglycerin was written about as early as 1846 and came into medical use in 1878. The drug nitroglycerin is a dilute form of the same chemical used as the explosive, nitroglycerin. Dilution makes it non-explosive. In 2022, it was the 196th most commonly prescribed medication in the United States, with more than 2 million prescriptions.
== Medical uses ==
Nitroglycerin is used for the treatment of angina, acute myocardial infarction, severe hypertension, and acute coronary artery spasms. It may be administered intravenously, as a sublingual spray/tablet, or as a patch applied to the skin.
=== Angina ===
Nitroglycerin is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of nitroglycerin, providing 24-hour release. However, the effectiveness of nitroglycerin is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus, nitroglycerin works best when used only in short-term, pulse dosing. Nitroglycerin is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose. It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack.
=== Other uses ===
Tentative evidence indicates efficacy of nitroglycerin in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.
Nitroglycerin is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.
Nitroglycerin has been used to decrease pain associated with dysmenorrhea.
Nitroglycerin was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada.
=== Tolerance ===
After long-term use for chronic conditions, nitrate tolerance—tolerance to agents such as nitroglycerin—may develop in a patient, reducing its effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of nitroglycerin or the need for higher doses of the drug to achieve the same effects, and was first described soon after the introduction of nitroglycerin in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis. These include endothelial and autonomic dysfunction.
The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including:
plasma volume expansion
impaired transformation of nitroglycerin into NO or related species
counteraction of nitroglycerin vasodilation by neurohormonal activation
oxidative stress
== Adverse events ==
Nitroglycerin can cause severe hypotension, reflex tachycardia, and severe headaches that necessitate analgesic intervention for pain relief, the painful nature of which can have a marked negative effect on patient compliance.
Nitroglycerin also can cause severe hypotension, circulatory collapse, and death if used together with vasodilator drugs that are used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil.
Nitroglycerin transdermal patches should be removed before defibrillation due to the risk of explosion or burns, but investigations have concluded that nitroglycerin patch explosions during defibrillation were due to the breakdown voltage of the metal mesh in some patches.
== Mechanism of action ==
Nitroglycerin is a prodrug which must be denitrated, with the nitrite anion or a related species further reduced to produce the active metabolite nitric oxide (NO). Organic nitrates that undergo these two steps within the body are called nitrovasodilators, and the denitration and reduction occur via a variety of mechanisms. The mechanism by which such nitrates produce NO is widely disputed. Some believe that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of nitroglycerin bioactivation.
The NO produced by this process is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Among other roles, cGMP serves as a substrate for a cGMP-dependent protein kinase that activates myosin light chain phosphatase. Thus, production of NO from exogenous sources such as nitroglycerin increases the level of cGMP within the cell, and stimulates dephosphorylation of myosin, which initiates relaxation of smooth muscle cells in blood vessels.
== History ==
It was known almost from the time of the first synthesis of nitroglycerin by Ascanio Sobrero in 1846 that handling and tasting of nitroglycerin could cause sudden intense headaches, which suggested a vasodilation effect. Constantine Hering developed a form of nitroglycerin in 1847 and advocated for its dosing as a treatment of a number of diseases; however, its use as a specific treatment for blood pressure and chest pain was not among these. This is primarily due to his deep rooted focus in homeopathy.
Following Thomas Brunton's discovery that amyl nitrite could be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to alleviate angina and reduce blood pressure, and showed that the accompanying headaches occurred as a result of overdose. Murrell began treating patients with small doses of nitroglycerin in 1878, and the substance was widely adopted after he published his results in The Lancet in 1879.
The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive.
Overdoses may generate methemoglobinemia.
== Society and culture ==
=== Brand names ===
In the United States, Nitrostat is marketed by Viatris after Upjohn was spun off from Pfizer.
== References ==
== Further reading == | Wikipedia/Nitroglycerin_(drug) |
Bromine mononitrate is an inorganic compound, derived from bromine and nitric acid with the chemical formula BrNO3. The compound is a yellow liquid, decomposes at temperatures above 0 °C.
This compounds is extremely reactive due to its intrinsic instability, which makes handling and synthesis challenging. Because of its explosive potential and corrosive character, this substance is mostly used for study in restricted laboratory settings. About its particular characteristics and uses outside of its use as a chemical research subject, not much is known.
== Synthesis ==
Bromine nitrate can be prepared by several methods:
1. Reaction of silver nitrate on an alcoholic solution of bromine:
Br2 + AgNO3 → BrNO3 + AgBr
2. Reaction of bromine chloride with chlorine nitrate at low temperatures:
BrCl + ClNO3 → BrNO3 + Cl2
== Physical properties ==
Bromine mononitrate forms an unstable yellow liquid that decomposes at temperatures above 0 °C.
The molecule has the structure BrONO2.
The compound is easily soluble in trichlorofluoromethane and carbon tetrachloride.
== Applications ==
Bromine nitrate plays a role in tropospheric chemistry as it reacts with sulfuric acid.
== References == | Wikipedia/Bromine_nitrate |
Industrial fermentation is the intentional use of fermentation in manufacturing processes. In addition to the mass production of fermented foods and drinks, industrial fermentation has widespread applications in chemical industry. Commodity chemicals, such as acetic acid, citric acid, and ethanol are made by fermentation. Moreover, nearly all commercially produced industrial enzymes, such as lipase, invertase and rennet, are made by fermentation with genetically modified microbes. In some cases, production of biomass itself is the objective, as is the case for single-cell proteins, baker's yeast, and starter cultures for lactic acid bacteria used in cheesemaking.
In general, fermentations can be divided into four types:
Production of biomass (viable cellular material)
Production of extracellular metabolites (chemical compounds)
Production of intracellular components (enzymes and other proteins)
Transformation of substrate (in which the transformed substrate is itself the product)
These types are not necessarily disjoined from each other, but provide a framework for understanding the differences in approach. The organisms used are typically microorganisms, particularly bacteria, algae, and fungi, such as yeasts and molds, but industrial fermentation may also involve cell cultures from plants and animals, such as CHO cells and insect cells. Special considerations are required for the specific organisms used in the fermentation, such as the dissolved oxygen level, nutrient levels, and temperature. The rate of fermentation depends on the concentration of microorganisms, cells, cellular components, and enzymes as well as temperature, pH and level of oxygen for aerobic fermentation. Product recovery frequently involves the concentration of the dilute solution.
== General process overview ==
In most industrial fermentations, the organisms or eukaryotic cells are submerged in a liquid medium; in others, such as the fermentation of cocoa beans, coffee cherries, and miso, fermentation takes place on the moist surface of the medium.
There are also industrial considerations related to the fermentation process. For instance, to avoid biological process contamination, the fermentation medium, air, and equipment are sterilized. Foam control can be achieved by either mechanical foam destruction or chemical anti-foaming agents. Several other factors must be measured and controlled such as pressure, temperature, agitator shaft power, and viscosity. An important element for industrial fermentations is scale up. This is the conversion of a laboratory procedure to an industrial process. It is well established in the field of industrial microbiology that what works well at the laboratory scale may work poorly or not at all when first attempted at large scale. It is generally not possible to take fermentation conditions that have worked in the laboratory and blindly apply them to industrial scale equipment. Although many parameters have been tested for use as scale up criteria, there is no general formula because of the variation in fermentation processes. The most important methods are the maintenance of constant power consumption per unit of broth and the maintenance of constant volumetric transfer rate.
=== Phases of growth ===
Fermentation begins once the growth medium is inoculated with the organism of interest. Growth of the inoculum does not occur immediately. This is the period of adaptation, called the lag phase. Following the lag phase, the rate of growth of the organism steadily increases, for a certain period—this period is the log or exponential phase.
After a phase of exponential growth, the rate of growth slows down, due to the continuously falling concentrations of nutrients and/or a continuously increasing (accumulating) concentrations of toxic substances. This phase, where the increase of the rate of growth is checked, is the deceleration phase. After the deceleration phase, growth ceases and the culture enters a stationary phase or a steady state. The biomass remains constant, except when certain accumulated chemicals in the culture chemically break down the cells in a process called chemolysis. Unless other microorganisms contaminate the culture, the chemical constitution remains unchanged. If all of the nutrients in the medium are consumed, or if the concentration of toxins is too great, the cells may become senescent and begin to die off. The total amount of biomass may not decrease, but the number of viable organisms will decrease.
=== Fermentation medium ===
The microbes or eukaryotic cells used for fermentation grow in (or on) specially designed growth medium which supplies the nutrients required by the organisms or cells. A variety of media exist, but invariably contain a carbon source, a nitrogen source, water, salts, and micronutrients. In the production of wine, the medium is grape must. In the production of bio-ethanol, the medium may consist mostly of whatever inexpensive carbon source is available.
Carbon sources are typically sugars or other carbohydrates, although in the case of substrate transformations (such as the production of vinegar) the carbon source may be an alcohol or something else altogether. For large scale fermentations, such as those used for the production of ethanol, inexpensive sources of carbohydrates, such as molasses, corn steep liquor, sugar cane juice, or sugar beet juice are used to minimize costs. More sensitive fermentations may instead use purified glucose, sucrose, glycerol or other sugars, which reduces variation and helps ensure the purity of the final product. Organisms meant to produce enzymes such as beta galactosidase, invertase or other amylases may be fed starch to select for organisms that express the enzymes in large quantity.
Fixed nitrogen sources are required for most organisms to synthesize proteins, nucleic acids and other cellular components. Depending on the enzyme capabilities of the organism, nitrogen may be provided as bulk protein, such as soy meal; as pre-digested polypeptides, such as peptone or tryptone; or as ammonia or nitrate salts. Cost is also an important factor in the choice of a nitrogen source. Phosphorus is needed for production of phospholipids in cellular membranes and for the production of nucleic acids. The amount of phosphate which must be added depends upon the composition of the broth and the needs of the organism, as well as the objective of the fermentation. For instance, some cultures will not produce secondary metabolites in the presence of phosphate.
Growth factors and trace nutrients are included in the fermentation broth for organisms incapable of producing all of the vitamins they require. Yeast extract is a common source of micronutrients and vitamins for fermentation media. Inorganic nutrients, including trace elements such as iron, zinc, copper, manganese, molybdenum, and cobalt are typically present in unrefined carbon and nitrogen sources, but may have to be added when purified carbon and nitrogen sources are used. Fermentations which produce large amounts of gas (or which require the addition of gas) will tend to form a layer of foam, since fermentation broth typically contains a variety of foam-reinforcing proteins, peptides or starches. To prevent this foam from occurring or accumulating, antifoaming agents may be added. Mineral buffering salts, such as carbonates and phosphates, may be used to stabilize pH near optimum. When metal ions are present in high concentrations, use of a chelating agent may be necessary.
Developing an optimal medium for fermentation is a key concept to efficient optimization. One-factor-at-a-time (OFAT) is the preferential choice that researchers use for designing a medium composition. This method involves changing only one factor at a time while keeping the other concentrations constant. This method can be separated into some sub groups. One is Removal Experiments. In this experiment all the components of the medium are removed one at a time and their effects on the medium are observed. Supplementation experiments involve evaluating the effects of nitrogen and carbon supplements on production. The final experiment is a replacement experiment. This involves replacing the nitrogen and carbon sources that show an enhancement effect on the intended production. Overall OFAT is a major advantage over other optimization methods because of its simplicity.
== Production of biomass ==
Microbial cells or biomass is sometimes the intended product of fermentation. Examples include single cell protein, bakers yeast, lactobacillus, E. coli, and others. In the case of single-cell protein, algae is grown in large open ponds which allow photosynthesis to occur. If the biomass is to be used for inoculation of other fermentations, care must be taken to prevent mutations from occurring.
== Production of extracellular metabolites ==
Metabolites can be divided into two groups: those produced during the growth phase of the organism, called primary metabolites and those produced during the stationary phase, called secondary metabolites. Some examples of primary metabolites are ethanol, citric acid, glutamic acid, lysine, vitamins and polysaccharides. Some examples of secondary metabolites are penicillin, cyclosporin A, gibberellin, and lovastatin.
=== Primary metabolites ===
Primary metabolites are compounds made during the ordinary metabolism of the organism during the growth phase. A common example is ethanol or lactic acid, produced during glycolysis. Citric acid is produced by some strains of Aspergillus niger as part of the citric acid cycle to acidify their environment and prevent competitors from taking over. Glutamate is produced by some Micrococcus species, and some Corynebacterium species produce lysine, threonine, tryptophan and other amino acids. All of these compounds are produced during the normal "business" of the cell and released into the environment. There is therefore no need to rupture the cells for product recovery.
=== Secondary metabolites ===
Secondary metabolites are compounds made in the stationary phase; penicillin, for instance, prevents the growth of bacteria which could compete with Penicillium molds for resources. Some bacteria, such as Lactobacillus species, are able to produce bacteriocins which prevent the growth of bacterial competitors as well. These compounds are of obvious value to humans wishing to prevent the growth of bacteria, either as antibiotics or as antiseptics (such as gramicidin S). Fungicides, such as griseofulvin are also produced as secondary metabolites. Typically secondary metabolites are not produced in the presence of glucose or other carbon sources which would encourage growth, and like primary metabolites are released into the surrounding medium without rupture of the cell membrane.
In the early days of the biotechnology industry, most biopharmaceutical products were made in E. coli; by 2004 more biopharmaceuticals were manufactured in eukaryotic cells, such as CHO cells, than in microbes, but used similar bioreactor systems. Insect cell culture systems came into use in the 2000s as well.
== Production of intracellular components ==
Of primary interest among the intracellular components are microbial enzymes: catalase, amylase, protease, pectinase, cellulase, hemicellulase, lipase, lactase, streptokinase and many others. Recombinant proteins, such as insulin, hepatitis B vaccine, interferon, granulocyte colony-stimulating factor, streptokinase and others are also made this way. The largest difference between this process and the others is that the cells must be ruptured (lysed) at the end of fermentation, and the environment must be manipulated to maximize the amount of the product. Furthermore, the product (typically a protein) must be separated from all of the other cellular proteins in the lysate to be purified.
== Transformation of substrate ==
Substrate transformation involves the transformation of a specific compound into another, such as in the case of phenylacetylcarbinol, and steroid biotransformation, or the transformation of a raw material into a finished product, in the case of food fermentations and sewage treatment.
=== Food fermentation ===
In the history of food, ancient fermented food processes, such as making bread, wine, cheese, curds, idli, dosa, among others can be dated to more than seven thousand years ago. They were developed long before humanity had any knowledge of the existence of the microorganisms involved. Some foods such as Marmite are the byproduct of the fermentation process, in this case in the production of beer.
=== Ethanol fuel ===
Fermentation is the main source of ethanol in the production of ethanol fuel. Common crops such as sugar cane, potato, cassava, and maize are fermented by yeast to produce ethanol which is further processed to become fuel.
=== Sewage treatment ===
In the process of sewage treatment, sewage is digested by enzymes secreted by bacteria. Solid organic matters are broken down into harmless, soluble substances and carbon dioxide. Liquids that result are disinfected to remove pathogens before being discharged into rivers or the sea or can be used as liquid fertilizers. Digested solids, known also as sludge, is dried and used as fertilizer. Gaseous byproducts such as methane can be utilized as biogas to fuel electrical generators. One advantage of bacterial digestion is that it reduces the bulk and odor of sewage, thus reducing space needed for dumping. The main disadvantage of bacterial digestion in sewage disposal is that it is a very slow process.
=== Agricultural feed ===
A wide variety of agroindustrial waste products can be fermented to use as food for animals, especially ruminants. Fungi have been employed to break down cellulosic wastes to increase protein content and improve in vitro digestibility.
== Precision fermentation ==
Precision fermentation is an approach to manufacturing specific functional products which intends to minimise the production of unwanted by-products through the application of synthetic biology, particularly by generating synthetic "cell factories" with engineered genomes and metabolic pathways optimised to produce the desired compounds as efficiently as possible with the available resources. Precision fermentation of genetically modified microorganisms may be used to manufacture proteins needed for cell culture media, providing for serum-free cell culture media in the manufacturing process of cultured meat. A 2021 publication showed that photovoltaic-driven microbial protein production could use 10 times less land for an equivalent amount of protein compared to soybean cultivation. Some Food Regulatory Agencies such as the FDA do not require the labeling of precision fermented foods as GMO since they are produced by, but do not contain the genetically engineered organisms. It is unclear how regulation will be handled in EU markets, with some Startups such as Formo and Those Vegan Cowboys forming the Food Fermentation Europe (FFE) alliance together with other alt-protein startups to seek regulatory approval.
== See also ==
== References ==
=== Bibliography === | Wikipedia/Industrial_fermentation |
Iodine nitrate is a chemical with formula INO3. It is a covalent molecule with a structure of I–O–NO2.
== Preparation ==
The compound was first produced by the reaction of mercury(II) nitrate and iodine in ether.
Other nitrate salts and solvents can also be used.
As a gas it is slightly unstable, decaying with a rate constant of −3.2×10−2 s−1. The possible formation of this chemical in the atmosphere and its ability to destroy ozone have been studied. Potential reactions in this context are:
IONO2 → IO + NO2
IONO2 → I + NO3
I + O3 → IO + O2
== References == | Wikipedia/Iodine_nitrate |
Ytterbium(III) nitrate is an inorganic compound, a salt of ytterbium and nitric acid with the chemical formula Yb(NO3)3. The compound forms colorless crystals, dissolves in water, and also forms crystalline hydrates.
== Synthesis ==
Reaction of ytterbium and nitric oxide in ethyl acetate:
Yb + 3 N2O4 → Yb(NO3)3 + 3 NO↑
Reaction of ytterbium hydroxide and nitric acid:
Yb(OH)3 + 3 HNO3 → Yb(NO3)3 + 3 H2O↑
== Physical properties ==
Ytterbium(III) nitrate forms colorless hygroscopic crystals.
Soluble in water and ethanol.
Forms crystalline hydrates of the composition Yb(NO3)3·nH2O, where n = 4, 5, or 6.
== Chemical properties ==
The hydrated ytterbium nitrate thermally decomposes to form YbONO3 and decomposes to ytterbium oxide upon further heating.
== Application ==
Ytterbium(III) nitrate hydrate is used for nanoscale coatings of carbon composites.
Also used to obtain metallic ytterbium and as a chemical reagent.
Used as a component for the production of ceramics and glass.
== References == | Wikipedia/Ytterbium(III)_nitrate |
Orthonitrate is a tetrahedral anion of nitrogen with the formula NO3−4. It was first identified in 1977 and is currently known in only two compounds, sodium orthonitrate (Na3NO4) and potassium orthonitrate (K3NO4). The corresponding oxoacid, orthonitric acid (H3NO4), is hypothetical and has never been observed. Sodium and potassium orthonitrate can be prepared by fusion of the nitrate and metal oxide under high temperatures and ideally high pressures (several GPa).
NaNO3 + Na2O → Na3NO4 (300 °C for 3 days)
The resulting orthonitrates are white solids which are extremely sensitive to moisture and CO2, decomposing within minutes to hydroxides, carbonates, and nitrates upon exposure to air.
Na3NO4 + CO2 → NaNO3 + Na2CO3
Na3NO4 + H2O → NaNO3 + 2 NaOH
The orthonitrate ion is tetrahedral with N–O bond lengths of 139 pm, which is unexpectedly short, indicating that polar interactions are shortening the bond. This short bond length parallels that of hypervalent oxyanions containing third-row elements like PO3−4 and SO2−4, for which pπ–dπ bonding was previously proposed as the explanation for the short bond length. Since 3d orbitals of nitrogen are much too high in energy to be involved in the case of orthonitrate, the shortness of the N–O bond in orthonitrate indicates that pπ–dπ bonding is likely not the most important explanation for the bond lengths of these heavier anions either.
== Other nitrogen oxyanions ==
nitrate, NO−3
nitrite, NO−2
== References == | Wikipedia/Orthonitrate |
Strontium nitrate is an inorganic compound composed of the elements strontium, nitrogen and oxygen with the formula Sr(NO3)2. This colorless solid is used as a red colorant and oxidizer in pyrotechnics.
== Preparation ==
Strontium nitrate is typically generated by the reaction of nitric acid on strontium carbonate.
2 HNO3 + SrCO3 → Sr(NO3)2 + H2O + CO2
== Uses ==
Like many other strontium salts, strontium nitrate is used to produce a rich red flame in fireworks and road flares. The oxidizing properties of this salt are advantageous in such applications.
Strontium nitrate can aid in eliminating and lessening skin irritations. When mixed with glycolic acid, strontium nitrate reduces the sensation of skin irritation significantly better than using glycolic acid alone.
== Biochemistry ==
As a divalent ion with an ionic radius similar to that of Ca2+ (1.13 Å and 0.99 Å respectively), Sr2+ ions resembles calcium's ability to traverse calcium-selective ion channels and trigger neurotransmitter release from nerve endings. It is thus used in electrophysiology experiments.
== In popular culture ==
In his short story "A Germ-Destroyer", Rudyard Kipling refers to strontium nitrate as the main ingredient of the titular fumigant.
== References == | Wikipedia/Strontium_nitrate |
Nitrogen trioxide or nitrate radical is an oxide of nitrogen with formula NO3, consisting of three oxygen atoms covalently bound to a nitrogen atom. This highly unstable blue compound has not been isolated in pure form, but can be generated and observed as a short-lived component of gas, liquid, or solid systems.
Like nitrogen dioxide NO2, it is a radical (a molecule with an unpaired valence electron), which makes it paramagnetic. It is the uncharged counterpart of the nitrate anion NO−3 and an isomer of the peroxynitrite radical OONO.
Nitrogen trioxide is an important intermediate in reactions between atmospheric components, including the destruction of ozone.
== History ==
The existence of the NO3 radical was postulated in 1881-1882 by Hautefeuille and Chappuis to explain the absorption spectrum of air subjected to a silent electrical discharge.
== Structure and properties ==
The neutral NO3 molecule appears to be planar, with three-fold rotational symmetry (symmetry group D3h); or possibly a resonance between three Y-shaped molecules.
The NO3 radical does not react directly with water, and is relatively unreactive towards closed-shell molecules, as opposed to isolated atoms and other radicals. It is decomposed by light of certain wavelengths into nitric oxide NO and oxygen O2.
The absorption spectrum of NO3 has a broad band for light with wavelengths from about 500 to 680 nm, with three salient peaks in the visible at 590, 662, and 623 nm. Absorption in the range 640–680 nm does not lead to dissociation but to fluorescence: specifically, from about 605 to 800 nm following excitation at 604.4 nm, and from about 662 to 800 nm following excitation at 661.8 nm. In water solution, another absorption band appears at about 330 nm (ultraviolet). An excited state NO*3 can be achieved by photons of wavelength less than 595 nm.
== Preparation ==
Nitrogen trioxide can be prepared in the gas phase by mixing nitrogen dioxide and ozone:
NO2 + O3 → NO3 + O2
This reaction can be performed also in the solid phase or water solutions, by irradiating frozen gas mixtures, flash photolysis and radiolysis of nitrate salts and nitric acid, and several other methods.
Nitrogen trioxide is a product of the photolysis of dinitrogen pentoxide N2O5, chlorine nitrate ClONO2, and peroxynitric acid HO2NO2 and its salts.
N2O5 → NO2 + NO3
2 ClONO2 → Cl2 + 2 NO3
== References == | Wikipedia/Nitrate_radical |
Sodium nitrate is the chemical compound with the formula NaNO3. This alkali metal nitrate salt is also known as Chile saltpeter (large deposits of which were historically mined in Chile) to distinguish it from ordinary saltpeter, potassium nitrate. The mineral form is also known as nitratine, nitratite or soda niter.
Sodium nitrate is a white deliquescent solid very soluble in water. It is a readily available source of the nitrate anion (NO3−), which is useful in several reactions carried out on industrial scales for the production of fertilizers, pyrotechnics, smoke bombs and other explosives, glass and pottery enamels, food preservatives (esp. meats), and solid rocket propellant. It has been mined extensively for these purposes.
== History ==
The first shipment of saltpeter to Europe arrived in England from Peru in 1820 or 1825, right after that country's independence from Spain, but did not find any buyers and was dumped at sea in order to avoid customs toll. With time, however, the mining of South American saltpeter became a profitable business (in 1859, England alone consumed 47,000 metric tons). Chile fought the War of the Pacific (1879–1884) against the allies Peru and Bolivia and took over their richest deposits of saltpeter. In 1919, Ralph Walter Graystone Wyckoff determined its crystal structure using X-ray crystallography.
== Occurrence ==
The largest accumulations of naturally occurring sodium nitrate are found in Chile and Peru, where nitrate salts are bound within mineral deposits called caliche ore. Nitrates accumulate on land through marine-fog precipitation and sea-spray oxidation/desiccation followed by gravitational settling of airborne NaNO3, KNO3, NaCl, Na2SO4, and I, in the hot-dry desert atmosphere. El Niño/La Niña extreme aridity/torrential rain cycles favor nitrates accumulation through both aridity and water solution/remobilization/transportation onto slopes and into basins; capillary solution movement forms layers of nitrates; pure nitrate forms rare veins. For more than a century, the world supply of the compound was mined almost exclusively from the Atacama desert in northern Chile until, at the turn of the 20th century, German chemists Fritz Haber and Carl Bosch developed a process for producing ammonia from the atmosphere on an industrial scale (see Haber process). With the onset of World War I, Germany began converting ammonia from this process into a synthetic Chilean saltpeter, which was as practical as the natural compound in production of gunpowder and other munitions. By the 1940s, this conversion process resulted in a dramatic decline in demand for sodium nitrate procured from natural sources.
Chile still has the largest reserves of caliche, with active mines in such locations as Valdivia, María Elena and Pampa Blanca, and there it used to be called white gold. Sodium nitrate, potassium nitrate, sodium sulfate and iodine are all obtained by the processing of caliche. The former Chilean saltpeter mining communities of Humberstone and Santa Laura were declared UNESCO World Heritage sites in 2005.
== Synthesis ==
Sodium nitrate is also synthesized industrially by neutralizing nitric acid with sodium carbonate or sodium bicarbonate:
2 HNO3 + Na2CO3 → 2 NaNO3 + H2O + CO2
HNO3 + NaHCO3 → NaNO3 + H2O + CO2
or also by neutralizing it with sodium hydroxide (however, this reaction is very exothermic):
HNO3 + NaOH → NaNO3 + H2O
or by mixing stoichiometric amounts of ammonium nitrate and sodium hydroxide, sodium bicarbonate or sodium carbonate:
NH4NO3 + NaOH → NaNO3 + NH4OH
NH4NO3 + NaHCO3 → NaNO3 + NH4HCO3
2NH4NO3 + Na2CO3 → 2NaNO3 + (NH4)2CO3
== Uses ==
Most sodium nitrate is used in fertilizers, where it supplies a water-soluble form of nitrogen. Its use, which is mainly outside of high-income countries, is attractive since it does not alter the pH of the soil. Another major use is as a complement to ammonium nitrate in explosives. Molten sodium nitrate and its solutions with potassium nitrate have good thermal stability (up to 600 °C) and high heat capacities. These properties are suitable for thermally annealing metals and for storing thermal energy in solar applications.
=== Food ===
Sodium nitrate is also a food additive used as a preservative and color fixative in cured meats and poultry; it is listed under its INS number 251 or E number E251. It is approved for use in the EU, US and Australia and New Zealand. Sodium nitrate should not be confused with sodium nitrite, which is also a common food additive and preservative used, for example, in deli meats.
=== Thermal storage ===
Sodium nitrate has also been investigated as a phase-change material for thermal energy recovery, owing to its relatively high melting enthalpy of 178 J/g. Examples of the applications of sodium nitrate used for thermal energy storage include solar thermal power technologies and direct steam generating parabolic troughs.
=== Steel coating ===
Sodium nitrate is used in a steel coating process in which it forms a surface of magnetite layer.
== Health concerns ==
Studies have shown a link between increased levels of nitrates and increased deaths from certain diseases including Alzheimer's disease, diabetes mellitus, stomach cancer, and Parkinson's disease: possibly through the damaging effect of nitrosamines on DNA; however, little has been done to control for other possible causes in the epidemiological results. Nitrosamines, formed in cured meats containing sodium nitrate and nitrite, have been linked to gastric cancer and esophageal cancer. Sodium nitrate and nitrite are associated with a higher risk of colorectal cancer.
Substantial evidence in recent decades, facilitated by an increased understanding of pathological processes and science, exists in support of the theory that processed meat increases the risk of colon cancer and that this is due to the nitrate content. A small amount of the nitrate added to meat as a preservative breaks down into nitrite, in addition to any nitrite that may also be added. The nitrite then reacts with protein-rich foods (such as meat) to produce carcinogenic NOCs (nitroso compounds). NOCs can be formed either when meat is cured or in the body as meat is digested.
However, several things complicate the otherwise straightforward understanding that "nitrates in food raise the risk of cancer". Processed meats have no fiber, vitamins, or phytochemical antioxidants, are high in sodium, may contain high fat, and are often fried or cooked at a temperature sufficient to degrade protein into nitrosamines. Nitrates are key intermediates and effectors in the primary vasculature signaling which is necessary for all mammals to survive.
== See also ==
Sodium nitrite
== References ==
== Further reading ==
Archer, Donald G. (2000). "Thermodynamic properties of the NaNO3 + H2O system". Journal of Physical and Chemical Reference Data. 29 (5): 1141–1156. Bibcode:2000JPCRD..29.1141A. doi:10.1063/1.1329317. ISSN 0047-2689.
Barnum, Dennis (2003). "Some history of nitrates". Journal of Chemical Education. 80 (12): 1393–. Bibcode:2003JChEd..80.1393B. doi:10.1021/ed080p1393.
Jones, Grinnell (1920). "Nitrogen: Its Fixation, Its Uses in Peace and War". The Quarterly Journal of Economics. 34 (3): 391–431.
Mullin, J. W. (1997). Crystallization. Butterworth-Heinemann. ISBN 978-0-7506-3759-6.
== External links ==
ATSDR – Case Studies in Environmental Medicine – Nitrate/Nitrite Toxicity U.S. Department of Health and Human Services (public domain)
FAO/WHO report
Calculators: surface tensions, and densities, molarities and molalities of aqueous sodium nitrate | Wikipedia/Sodium_nitrate |
Zirconium nitrate is a volatile anhydrous transition metal nitrate salt of zirconium with formula Zr(NO3)4. It has alternate names of zirconium tetranitrate, or zirconium(IV) nitrate.
It has a UN number of UN 2728 and is class 5.1, meaning oxidising substance.
== Formation ==
The anhydrous salt can be made from zirconium tetrachloride reacting with dinitrogen pentoxide.
ZrCl4 + 4 N2O5 → Zr(NO3)4 + 4ClNO2
The product can be purified by sublimation in a vacuum. A contaminating substance in this is nitronium pentanitratozirconate. (NO2)Zr(NO3)5.
Zirconium nitrate pentahydrate Zr(NO3)4·5H2O can be formed by dissolving zirconium dioxide in nitric acid and then evaporating the solution until it is dry. However it is easier to crystallise zirconyl nitrate trihydrate ZrO(NO3)2·3H2O from such a solution.
Zirconium is highly resistant to nitric acid even in the presence of other impurities and high temperatures. So zirconium nitrate is not made by dissolving zirconium metal in nitric acid.
== Properties ==
Zirconium nitrate pentahydrate dissolves easily in water and alcohol. It is acidic in aqueous solution, and a base such as ammonium hydroxide will cause zirconium hydroxide to precipitate. The pentahydrate crystals have a refractive index of 1.6.
== Related substances ==
Related substances are zirconium nitrate complexes. Zr(NO3)3(H2O)+3 has a tricapped trigonal prismatic structure, with the nitrates connected by two oxygen atoms each (bidentate). The pentanitrato complex Zr(NO3)−5 has all the nitrate groups bidentate, and has a bicapped square antiprism shape.
NO2[Zr(NO3)3·3H2O]2(NO3)3 crystallizes in the hexagonal system, space group P3c1, with unit cell dimensions a = 10.292 Å, b = 10.292 Å, c = 14.84 Å, volume 1632.2 Å3 with 2 formulae per unit cell, density = 2.181.
CsZr(NO3)5 crystallizes in the monoclinic system, space group P21/n, with unit cell dimensions a = 7.497 Å, b = 11.567 Å, c = 14.411 Å, β=96.01°, volume 1242.8 Å3 with 4 formulae per cell, density = 2.855.
(NH4)Zr(NO3)5·HNO3 crystallizes in the orthorhombic system, space group Pna21 with unit cell dimensions a=14.852 Å, b = 7.222 Å, c = 13.177 Å, volume 1413.6 Å3 with 4 formulae per cell, density = 2.267.
A mixed nitronium, nitrosonium pentanitratozirconate crystallizing in the tetragonal system also exists.
== Use ==
Zirconium nitrate is manufactured by a number of chemical suppliers. It is used as a source of zirconium for other salts, as an analytical standard, or as a preservative. Zirconium nitrate and nitronium pentanitratozirconate can be used as chemical vapour deposition precursors as they are volatile, and decompose above 100 °C to form zirconia. At 95 °C, zirconium nitrate sublimes with a pressure of 0.2 mm of Hg and can be deposited as zirconium dioxide on silicon at 285 °C. It has the advantage in that it is a single source, meaning it does not have to be mixed with other materials like oxygen, and decomposes at a relatively low temperature, and does not contaminate the surface with other elements such as hydrogen or fluorine.
Zirconium free from hafnium is required for nuclear reactor construction. One way to achieve this is via a mixed aqueous solution of hafnium nitrate and zirconium nitrate, which can be separated by partitioning the zirconium into tributylphosphate dissolved in kerosene.
Zirconium nitrate can be used as a Lewis acid catalyst in the formation of N-substituted pyrroles.
Anhydrous zirconium nitrate can nitrate some organic aromatic compounds in an unusual way. Quinoline is nitrated to 3-nitroquinoline and 7-nitroquinoline. Pyridine is nitrated to 3-nitropyridine and 4-nitropyridine.
== References == | Wikipedia/Zirconium_nitrate |
Vanadyl nitrate, also called vanadium oxytrinitrate or vanadium oxynitrate is an inorganic compound of vanadium in the +5 oxidation state with nitrate ligands and oxygen. The formula is VO(NO3)3. It is a pale yellow viscous liquid.
== Production ==
It is made by soaking vanadium pentoxide in liquid dinitrogen pentoxide for durations around two days at room temperature. The yield for this method is about 85%.
V2O5 + 3 N2O5 → 2 VO(NO3)3.
Purification can be achieved by vacuum distillation.
Mononitratodioxovanadium (VO2NO3) is an intermediate in this synthesis. It is a brick red solid.
Vanadyl nitrate can also be made from vanadyl trichloride VOCl3 and dinitrogen pentoxide.
== Structure ==
VO(NO3)3 has a distorted pentagonal bipyramid shape with idealized Cs (mirror) symmetry. The vanadium oxygen bond (157.2 pm) is typical for vanadyl(V). Two nitrate groups in the pentagonal plane are bidentate (V-O distances range from 199 to 206 pm). The third nitrate spans the pentagonal plane (197 pm) to the position trans to oxo (223 pm).
== Properties ==
Vanadyl nitrate dissolves in dichloromethane, nitromethane, carbon tetrachloride, and saturated hydrocarbons. 1-Hexene, or other unsaturated hydrocarbons ignite upon contact with vanadyl nitrate. Upon contact with water, it irreversibly hydrolyzes, releasing nitric acid.
The ultraviolet spectrum of the liquid shows an absorption band peaking at 208 nm with a shoulder at 242 nm. At 55 °C the gaseous vanadyl nitrate has absorption bands also at 486, 582 and 658 nm in the visual light spectrum. in the infrared region, liquid vanadyl nitrate absorbs at 1880, 1633, 1612, 1560, 1306, 1205, 1016, 996, 965, 895, 783, 632, 457, 357, 301, 283, 234, 193, 133, 93 and 59 cm−1. Gaseous vanadyl nitrate has absorption bands at 775, 783, 786, 962.5, 994.4, 997.5, 1000.5, 1006.2, 1012, 1016.3, 1020, 1198, 1211, 1216.3, 1564, 1612, 1629, 1632, 1635, 1648 and 1888 cm−1. Many of these bands are due to stretching in nitrogen–oxygen bonds, but 1016.3 cm−1 is due to the double vanadium–oxygen bond. 786 is due to out of phase wagging in N-O, and 775 is due to deformation in O-N=O in the mirror plane.
== Reactions ==
It is a nitrating agent for aromatic compounds. Reactions proceed at room temperature. Often dichloromethane is used as an inert solvent. Nitrotoluene, methyl benzoate and benzoic acid are nitrated by prolonged exposure over a few days. Benzonitrile does not react.
Vanadyl nitrate form a solid pale yellow adduct with boron trifluoride. An adduct is also formed with acetonitrile.
== References ==
== Other reading ==
Gmelin, Syst No 48, Teil A & Teil B (Lieferung 1 & 2) (1967); Teil A (Lieferung 1) & Teil A (Lieferung 2) (1968);& Erganzungwerk (Band2)(1971)
M. Schmeisser, "Chemical Abstracts", (1955), 49, 10873
L. Bretherick, Ed, "Hazards in the Chemical Laboratory", Royal Society of Chemistry, London, Engl (1979), pg. 1160 | Wikipedia/Vanadyl_nitrate |
Potassium nitrate is a chemical compound with a sharp, salty, bitter taste and the chemical formula KNO3. It is a potassium salt of nitric acid. This salt consists of potassium cations K+ and nitrate anions NO−3, and is therefore an alkali metal nitrate. It occurs in nature as a mineral, niter (or nitre outside the United States). It is a source of nitrogen, and nitrogen was named after niter. Potassium nitrate is one of several nitrogen-containing compounds collectively referred to as saltpetre (or saltpeter in the United States).
Major uses of potassium nitrate are in fertilizers, tree stump removal, rocket propellants and fireworks. It is one of the major constituents of traditional gunpowder (black powder). In processed meats, potassium nitrate reacts with hemoglobin and myoglobin generating a red color.
== Etymology ==
Nitre, or potassium nitrate, because of its early and global use and production, has many names.
As for nitrate, Egyptian and Hebrew words for it had the consonants n-t-r, indicating likely cognation in the Greek nitron, which was Latinised to nitrum or nitrium. Thence Old French had niter and Middle English nitre. By the 15th century, Europeans referred to it as saltpetre, specifically Indian saltpetre (Chilean saltpetre is sodium nitrate) and later as nitrate of potash, as the chemistry of the compound was more fully understood.
The Arabs called it "Chinese snow" (Arabic: ثلج الصين, romanized: thalj al-ṣīn) as well as bārūd (بارود), a term of uncertain origin that later came to mean gunpowder. It was called "Chinese salt" by the Iranians/Persians or "salt from Chinese salt marshes" (Persian: نمک شوره چينی namak shūra chīnī).: 335 The Tiangong Kaiwu, published in the 17th century by members of the Qing dynasty, detailed the production of gunpowder and other useful products from nature.
== Historical production ==
=== From mineral sources ===
In Mauryan India saltpeter manufacturers formed the Nuniya & Labana
caste. Saltpeter finds mention in Kautilya's Arthashastra (compiled 300BC – 300AD), which mentions using its poisonous smoke as a weapon of war, although its use for propulsion did not appear until medieval times.
A purification process for potassium nitrate was outlined in 1270 by the chemist and engineer Hasan al-Rammah of Syria in his book al-Furusiyya wa al-Manasib al-Harbiyya (The Book of Military Horsemanship and Ingenious War Devices). In this book, al-Rammah describes first the purification of barud (crude saltpeter mineral) by boiling it with minimal water and using only the hot solution, then the use of potassium carbonate (in the form of wood ashes) to remove calcium and magnesium by precipitation of their carbonates from this solution, leaving a solution of purified potassium nitrate, which could then be dried. This was used for the manufacture of gunpowder and explosive devices. The terminology used by al-Rammah indicated the gunpowder he wrote about originated in China.
At least as far back as 1845, nitratite deposits were exploited in Chile and California.
=== From caves ===
Major natural sources of potassium nitrate were the deposits crystallizing from cave walls and the accumulations of bat guano in caves. Extraction is accomplished by immersing the guano in water for a day, filtering, and harvesting the crystals in the filtered water. Traditionally, guano was the source used in Laos for the manufacture of gunpowder for Bang Fai rockets.
Calcium nitrate, or lime saltpetre, was discovered on the walls of stables, from the urine of barnyard animals.
=== Nitraries ===
Potassium nitrate was produced in a nitrary or "saltpetre works". The process involved burial of excrements (human or animal) in a field beside the nitraries, watering them and waiting until leaching allowed saltpeter to migrate to the surface by efflorescence. Operators then gathered the resulting powder and transported it to be concentrated by ebullition in the boiler plant.
Besides "Montepellusanus", during the thirteenth century (and beyond) the only supply of saltpeter across Christian Europe (according to "De Alchimia" in 3 manuscripts of Michael Scot, 1180–1236) was "found in Spain in Aragon in a certain mountain near the sea".: 89, 311
In 1561, Elizabeth I, Queen of England and Ireland, who was at war with Philip II of Spain, became unable to import saltpeter (of which the Kingdom of England had no home production), and had to pay "300 pounds gold" to the German captain Gerrard Honrik for the manual "Instructions for making saltpeter to growe" (the secret of the "Feuerwerkbuch" -the nitraries-).
=== Nitre bed ===
A nitre bed is a similar process used to produce nitrate from excrement. Unlike the leaching-based process of the nitrary, however, one mixes the excrements with soil and waits for soil microbes to convert amino-nitrogen into nitrates by nitrification. The nitrates are extracted from soil with water and then purified into saltpeter by adding wood ash. The process was discovered in the early 15th century and was very widely used until the Chilean mineral deposits were found.
The Confederate side of the American Civil War had a significant shortage of saltpeter. As a result, the Nitre and Mining Bureau was set up to encourage local production, including by nitre beds and by providing excrement to government nitraries. On November 13, 1862, the government advertised in the Charleston Daily Courier for 20 or 30 "able bodied Negro men" to work in the new nitre beds at Ashley Ferry, S.C. The nitre beds were large rectangles of rotted manure and straw, moistened weekly with urine, "dung water", and liquid from privies, cesspools and drains, and turned over regularly. The National Archives published payroll records that account for more than 29,000 people compelled to such labor in the state of Virginia. The South was so desperate for saltpeter for gunpowder that one Alabama official reportedly placed a newspaper ad asking that the contents of chamber pots be saved for collection. In South Carolina, in April 1864, the Confederate government forced 31 enslaved people to work at the Ashley Ferry Nitre Works, outside Charleston.
Perhaps the most exhaustive discussion of the niter-bed production is the 1862 LeConte text. He was writing with the express purpose of increasing production in the Confederate States to support their needs during the American Civil War. Since he was calling for the assistance of rural farming communities, the descriptions and instructions are both simple and explicit. He details the "French Method", along with several variations, as well as a "Swiss method". N.B. Many references have been made to a method using only straw and urine, but there is no such method in this work.
==== French method ====
Turgot and Lavoisier created the Régie des Poudres et Salpêtres a few years before the French Revolution. Niter-beds were prepared by mixing manure with either mortar or wood ashes, common earth and organic materials such as straw to give porosity to a compost pile typically 4 feet (1.2 m) high, 6 feet (1.8 m) wide, and 15 feet (4.6 m) long. The heap was usually under a cover from the rain, kept moist with urine, turned often to accelerate the decomposition, then finally leached with water after approximately one year, to remove the soluble calcium nitrate which was then converted to potassium nitrate by filtering through potash.
==== Swiss method ====
Joseph LeConte describes a process using only urine and not dung, referring to it as the Swiss method. Urine is collected directly, in a sandpit under a stable. The sand itself is dug out and leached for nitrates which are then converted to potassium nitrate using potash, as above.
=== From nitric acid ===
From 1903 until the World War I era, potassium nitrate for black powder and fertilizer was produced on an industrial scale from nitric acid produced using the Birkeland–Eyde process, which used an electric arc to oxidize nitrogen from the air. During World War I the newly industrialized Haber process (1913) was combined with the Ostwald process after 1915, allowing Germany to produce nitric acid for the war after being cut off from its supplies of mineral sodium nitrates from Chile (see nitratite).
== Modern production ==
Potassium nitrate can be made by combining ammonium nitrate and potassium hydroxide.
NH4NO3 + KOH → NH3 + KNO3 + H2O
An alternative way of producing potassium nitrate without a by-product of ammonia is to combine ammonium nitrate, found in instant ice packs, and potassium chloride, easily obtained as a sodium-free salt substitute.
NH4NO3 + KCl → NH4Cl + KNO3
Potassium nitrate can also be produced by neutralizing nitric acid with potassium hydroxide. This reaction is highly exothermic.
KOH + HNO3 → KNO3 + H2O
On industrial scale it is prepared by the double displacement reaction between sodium nitrate and potassium chloride.
NaNO3 + KCl → NaCl + KNO3
== Properties ==
Potassium nitrate has an orthorhombic crystal structure at room temperature, which transforms to a trigonal system at 128 °C (262 °F). On cooling from 200 °C (392 °F), another trigonal phase forms between 124 °C (255 °F) and 100 °C (212 °F).
Sodium nitrate is isomorphous with calcite, the most stable form of calcium carbonate, whereas room-temperature potassium nitrate is isomorphous with aragonite, a slightly less stable polymorph of calcium carbonate. The difference is attributed to the similarity in size between nitrate (NO−3) and carbonate (CO2−3) ions and the fact that the potassium ion (K+) is larger than sodium (Na+) and calcium (Ca2+) ions.
In the room-temperature structure of potassium nitrate, each potassium ion is surrounded by 6 nitrate ions. In turn, each nitrate ion is surrounded by 6 potassium ions.
Potassium nitrate is moderately soluble in water, but its solubility increases with temperature. The aqueous solution is almost neutral, exhibiting pH 6.2 at 14 °C (57 °F) for a 10% solution of commercial powder. It is not very hygroscopic, absorbing about 0.03% water in 80% relative humidity over 50 days. It is insoluble in alcohol and is not poisonous; it can react explosively with reducing agents, but it is not explosive on its own.
=== Thermal decomposition ===
Between 550–790 °C (1,022–1,454 °F), potassium nitrate reaches a temperature-dependent equilibrium with potassium nitrite:
2 KNO3 ⇌ 2 KNO2 + O2
== Uses ==
Potassium nitrate has a wide variety of uses, largely as a source of nitrate.
=== Nitric acid production ===
Historically, nitric acid was produced by combining sulfuric acid with nitrates such as saltpeter. In modern times this is reversed: nitrates are produced from nitric acid produced via the Ostwald process.
=== Oxidizer ===
The most famous use of potassium nitrate is probably as the oxidizer in blackpowder. From the most ancient times until the late 1880s, blackpowder provided the explosive power for all the world's firearms. After that time, small arms and large artillery increasingly began to depend on cordite, a smokeless powder. Blackpowder remains in use today in black powder rocket motors, but also in combination with other fuels like sugars in "rocket candy" (a popular amateur rocket propellant). It is also used in fireworks such as smoke bombs. It is also added to cigarettes to maintain an even burn of the tobacco and is used to ensure complete combustion of paper cartridges for cap and ball revolvers. It can also be heated to several hundred degrees to be used for niter bluing, which is less durable than other forms of protective oxidation, but allows for specific coloration of steel parts, such as screws, pins, and other small parts of firearms.
=== Meat processing ===
Potassium nitrate has been a common ingredient of salted meat since antiquity or the Middle Ages. The widespread adoption of nitrate use is more recent and is linked to the development of large-scale meat processing. The use of potassium nitrate has been mostly discontinued because it gives slow and inconsistent results compared with sodium nitrite preparations such as "Prague powder" or pink "curing salt". Even so, potassium nitrate is still used in some food applications, such as salami, dry-cured ham, charcuterie, and (in some countries) in the brine used to make corned beef (sometimes together with sodium nitrite). In the Shetland Islands (UK) it is used in the curing of mutton to make reestit mutton, a local delicacy. When used as a food additive in the European Union, the compound is referred to as E252; it is also approved for use as a food additive in the United States and Australia and New Zealand (where it is listed under its INS number 252).
==== Possible cancer risk ====
Since October 2015, WHO classifies processed meat as Group 1 carcinogen (based on epidemiological studies, convincingly carcinogenic to humans).
In April 2023 the French Court of Appeals of Limoges confirmed that food-watch NGO Yuka was legally legitimate in describing Potassium Nitrate E249 to E252 as a "cancer risk", and thus rejected an appeal by the French charcuterie industry against the organisation.
=== Fertilizer ===
Potassium nitrate is used in fertilizers as a source of nitrogen and potassium – two of the macronutrients for plants. When used by itself, it has an NPK rating of 13-0-44.
=== Pharmacology ===
Used in some toothpastes for sensitive teeth. It has been used since 1980, although the efficacy is not strongly supported by the literature.
Used historically to treat asthma. Used in some toothpastes to relieve asthma symptoms.
Used in Thailand as main ingredient in kidney tablets to relieve the symptoms of cystitis, pyelitis and urethritis.
Combats high blood pressure and was once used as a hypotensive.
=== Other uses ===
Used as an electrolyte in a salt bridge.
Active ingredient of condensed aerosol fire suppression systems. When burned with the free radicals of a fire's flame, it produces potassium carbonate.
Works as an aluminium cleaner.
Component (usually about 98%) of some tree stump removal products. It accelerates the natural decomposition of the stump by supplying nitrogen for the fungi attacking the wood of the stump.
In heat treatment of metals as a medium temperature molten salt bath, usually in combination with sodium nitrite. A similar bath is used to produce a durable blue/black finish typically seen on firearms. Its oxidizing quality, water solubility, and low cost make it an ideal short-term rust inhibitor.
In glass toughening: molten potassium nitrate bath is used to increase glass strength and scratch-resistance.
To induce flowering of mango trees in the Philippines.
Thermal storage medium in power generation systems. Sodium and potassium nitrate salts are stored in a molten state with the solar energy collected by the heliostats at the Gemasolar Thermosolar Plant. Ternary salts, with the addition of calcium nitrate or lithium nitrate, have been found to improve the heat storage capacity in the molten salts.
As a source of potassium ions for exchange with sodium ions in chemically strengthened glass.
As an oxidizer in model rocket fuel called Rocket candy.
As a constituent in homemade smoke bombs.
== In folklore and popular culture ==
Potassium nitrate was once thought to induce impotence, and is still rumored to be in institutional food (such as military fare). There is no scientific evidence for such properties. In Bank Shot, El (Joanna Cassidy) propositions Walter Ballantine (George C. Scott), who tells her that he has been fed saltpeter in prison. In One Flew Over the Cuckoo's Nest, Randle is asked by the nurses to take his medications, but not knowing what they are, he mentions he does not want anyone to "slip me saltpeter". He then proceeds to imitate the motions of masturbation.
In 1776, John Adams asks his wife Abigail to make saltpeter for the Continental Army. She, eventually, is able to do so in exchange for pins for sewing.
In the Star Trek episode "Arena", Captain Kirk injures a gorn using a rudimentary cannon that he constructs using potassium nitrate as a key ingredient of gunpowder.
In 21 Jump Street, Jenko, played by Channing Tatum, gives a rhyming presentation about potassium nitrate for his chemistry class.
In Eating Raoul, Paul hires a dominatrix to impersonate a nurse and trick Raoul into consuming saltpeter in a ploy to reduce his sexual appetite for his wife.
In The Simpsons episode "El Viaje Misterioso de Nuestro Jomer (The Mysterious Voyage of Our Homer)", Mr. Burns is seen pouring saltpeter into his chili entry, titled Old Elihu's Yale-Style Saltpeter Chili.
In the Sharpe novel series by Bernard Cornwell, numerous mentions are made of an advantageous supply of saltpeter from India being a crucial component of British military supremacy in the Napoleonic Wars. In Sharpe's Havoc, the French Captain Argenton laments that France needs to scrape its supply from cesspits.
In the Dr. Stone anime and manga series, the struggle for control over a natural saltpeter source from guano features prominently in the plot.
In the farming lore from the Corn Belt of the 1800s, drought-killed corn in manured fields could accumulate saltpeter to the extent that upon opening the stalk for examination it would "fall as a fine powder upon the table".
In the Slovenian short story Martin Krpan from Vrh pri Sveti Trojici, the titular character and Slovene folk hero Martin Krpan illegally smuggles "English salt" for a living. The exact nature of "English salt" is a matter of debate, but it may have been a euphemism for potassium nitrate (saltpeter) due to its role in manufacturing gunpowder.
In Dexter: Original Sin's first episode, Dexter's first victim uses potassium nitrate to kill her victims.
In Gabriel García Márquez’s novella Chronicle of a Death Foretold, the character Bayardo San Román is described as having “a skin slowly roasted by saltpeter”.
== See also ==
History of gunpowder
Humberstone and Santa Laura Saltpeter Works
Niter, a mineral form of potassium nitrate
Nitratine
Nitrocellulose
Potassium perchlorate
== References ==
== Bibliography ==
Barnum, Dennis W. (December 2003). "Some History of Nitrates". Journal of Chemical Education. 80 (12): 1393. Bibcode:2003JChEd..80.1393B. doi:10.1021/ed080p1393.
David Cressy. Saltpeter: The Mother of Gunpowder (Oxford University Press, 2013) 237 pp online review by Robert Tiegs
Alan Williams. "The production of saltpeter in the Middle Ages", Ambix, 22 (1975), pp. 125–33. Maney Publishing, ISSN 0002-6980.
== External links ==
"Saltpetre" . Encyclopædia Britannica. Vol. XXI (9th ed.). 1886. p. 235.
International Chemical Safety Card 018402216 | Wikipedia/Potassium_nitrate |
Lead(II) nitrate is an inorganic compound with the chemical formula Pb(NO3)2. It commonly occurs as a colourless crystal or white powder and, unlike most other lead(II) salts, is soluble in water.
Known since the Middle Ages by the name plumbum dulce, the production of lead(II) nitrate from either metallic lead or lead oxide in nitric acid was small-scale, for direct use in making other lead compounds. In the nineteenth century lead(II) nitrate began to be produced commercially in Europe and the United States. Historically, the main use was as a raw material in the production of pigments for lead paints, but such paints have been superseded by less toxic paints based on titanium dioxide. Other industrial uses included heat stabilization in nylon and polyesters, and in coatings of photothermographic paper. Since around the year 2000, lead(II) nitrate has begun to be used in gold cyanidation.
Lead(II) nitrate is toxic and must be handled with care to prevent inhalation, ingestion and skin contact. Due to its hazardous nature, the limited applications of lead(II) nitrate are under constant scrutiny.
== History ==
Lead nitrate was first identified in 1597 by the alchemist Andreas Libavius, who called the substance plumbum dulce, meaning "sweet lead", because of its taste. It is produced commercially by reaction of metallic lead with concentrated nitric acid in which it is sparingly soluble. It has been produced as a raw material for making pigments such as chrome yellow (lead(II) chromate, PbCrO4) and chrome orange (basic lead(II) chromate, Pb2CrO5) and Naples yellow. These pigments were used for dyeing and printing calico and other textiles. It has been used as an oxidizer in black powder and together with lead azide in special explosives.
== Production ==
Lead nitrate is produced by reaction of lead(II) oxide with concentrated nitric acid:
PbO + 2 HNO3 (concentrated) → Pb(NO3)2↓ + H2O
It may also be obtained by evaporation of the solution obtained by reacting metallic lead with dilute nitric acid.
Pb + 4 HNO3 → Pb(NO3)2 + 2 NO2 + 2 H2O
Solutions and crystals of lead(II) nitrate are formed in the processing of lead–bismuth wastes from lead refineries.
== Structure ==
The crystal structure of solid lead(II) nitrate has been determined by neutron diffraction. The compound crystallizes in the cubic system with the lead atoms in a face-centred cubic system. Its space group is Pa3Z=4 (Bravais lattice notation), with each side of the cube with length 784 picometres.
The black dots represent the lead atoms, the white dots the nitrate groups 27 picometres above the plane of the lead atoms, and the blue dots the nitrate groups the same distance below this plane. In this configuration, every lead atom is bonded to twelve oxygen atoms (bond length: 281 pm). All N–O bond lengths are identical, at 127 picometres.
Research interest in the crystal structure of lead(II) nitrate was partly based on the possibility of free internal rotation of the nitrate groups within the crystal lattice at elevated temperatures, but this did not materialise.
== Chemical properties and reactions ==
Lead nitrate is an oxidizer and has been used as such in pyrotechnics. It is soluble in water and dilute nitric acid.
Basic nitrates are formed when alkali is added to a solution. Pb2(OH)2(NO3)2 is the predominant species formed at low pH. At higher pH Pb6(OH)5NO3 is formed. The cation Pb6O(OH)64+ is unusual in having an oxide ion inside a cluster of 3 face-sharing PbO4 tetrahedra.
There is no evidence for the formation of the hydroxide, Pb(OH)2, in aqueous solution below pH 12.
Solutions of lead nitrate can be used to form co-ordination complexes. Lead(II) is a hard acceptor; it forms stronger complexes with nitrogen and oxygen electron-donating ligands. For example, combining lead nitrate and pentaethylene glycol (shortened to EO5 in the referenced paper) in a solution of acetonitrile and methanol followed by slow evaporation produced the compound [Pb(NO3)2EO5]. In the crystal structure for this compound, the EO5 chain is wrapped around the lead ion in an equatorial plane similar to that of a crown ether. The two bidentate nitrate ligands are in trans configuration. The total coordination number is 10, with the lead ion in a bicapped square antiprism molecular geometry.
The complex formed by lead nitrate with a bithiazole bidentate N-donor ligand is binuclear. The crystal structure shows that the nitrate group forms a bridge between two lead atoms. One aspect of this type of complexes is the presence of a physical gap in the coordination sphere; i.e., the ligands are not placed symmetrically around the metal ion. This is potentially due to a lone pair of lead electrons, also found in lead complexes with an imidazole ligand.
== Applications ==
Lead nitrate has been used as a heat stabiliser in nylon and polyesters, as a coating for photothermographic paper, and in rodenticides.
Heating lead nitrate is convenient means of making nitrogen dioxide:
2
Pb
(
NO
3
)
2
→
Δ
2
PbO
+
4
NO
2
+
O
2
{\displaystyle {\ce {2 Pb(NO_3)_2->[\Delta]2PbO + 4NO_2 +O_2}}}
In the gold cyanidation process, addition of lead(II) nitrate solution improves the leaching process. Only limited amounts (10 to 100 milligrams lead nitrate per kilogram gold) are required.
In organic chemistry, it may be used in the preparation of isothiocyanates from dithiocarbamates. Its use as a bromide scavenger during SN1 substitution has been reported.
== Safety ==
Lead(II) nitrate is toxic, and ingestion may lead to acute lead poisoning, as is applicable for all soluble lead compounds. All inorganic lead compounds are classified by the International Agency for Research on Cancer (IARC) as probably carcinogenic to humans (Category 2A). They have been linked to renal cancer and glioma in experimental animals and to renal cancer, brain cancer and lung cancer in humans, although studies of workers exposed to lead are often complicated by concurrent exposure to arsenic. Lead is known to substitute for zinc in a number of enzymes, including δ-aminolevulinic acid dehydratase (porphobilinogen synthase) in the haem biosynthetic pathway and pyrimidine-5′-nucleotidase, important for the correct metabolism of DNA and can therefore cause fetal damage.
== References ==
== External links ==
Woodbury, William D. (1982). "Lead". Mineral Yearbook Metals and Minerals. Bureau of Mines: 515–42. Retrieved 2008-01-18.
"Lead". NIOSH Pocket Guide to Chemical Hazards. National Institute for Occupational Safety and Health. September 2005. NIOSH 2005-149. Retrieved 2008-01-19.
"Lead and Lead Compounds Fact Sheet". National Pollutant Inventory. Australian Government, Department of the Environment and Water Resources. July 2007. Archived from the original on January 11, 2008. Retrieved 2008-01-19.
"Lead". A Healthy Home Environment, Health Hazards. US Alliance for healthy homes. Archived from the original on 2008-02-20. Retrieved 2008-01-19.
Material Safety Data Sheets
MSDS for lead nitrate, PTCL, Oxford University
MSDS for lead nitrate, Science Stuff Inc
MSDS for lead nitrate, Iowa State University | Wikipedia/Lead(II)_nitrate |
A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted (ADME).
Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract. A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects.
== History ==
Many herbal extracts historically used in medicine contain glycosides (sugar derivatives) of the active agent, which are hydrolyzed in the intestines to release the active and more bioavailable aglycone. For example, salicin is a β-D-glucopyranoside that is cleaved by esterases to release salicylic acid. Aspirin, acetylsalicylic acid, first made by Felix Hoffmann at Bayer in 1897, is a synthetic prodrug of salicylic acid. However, in other cases, such as codeine and morphine, the administered drug is enzymatically activated to form sugar derivatives (morphine-glucuronides) that are more active than the parent compound.
The first synthetic antimicrobial drug, arsphenamine, discovered in 1909 by Sahachiro Hata in the laboratory of Paul Ehrlich, is not toxic to bacteria until it has been converted to an active form by the body. Likewise, prontosil, the first sulfa drug (discovered by Gerhard Domagk in 1932), must be cleaved in the body to release the active molecule, sulfanilamide. Since that time, many other examples have been identified.
Terfenadine, the first non-sedating antihistamine, had to be withdrawn from the market because of the small risk of a serious side effect. However, terfenadine was discovered to be the prodrug of the active molecule, fexofenadine, which does not carry the same risks as the parent compound. Therefore, fexofenadine could be placed on the market as a safe replacement for the original drug.
Loratadine, another non-sedating antihistamine, is the prodrug of desloratadine, which is largely responsible for the antihistaminergic effects of the parent compound. However, in this case the parent compound does not have the side effects associated with terfenadine, and so both loratadine and its active metabolite, desloratadine, are currently marketed.
== Recent prodrugs ==
Approximately 10% of all marketed drugs worldwide can be considered prodrugs. Since 2008, at least 30 prodrugs have been approved by the FDA. Seven prodrugs were approved in 2015 and six in 2017. Examples of recently approved prodrugs are such as dabigatran etexilate (approved in 2010), gabapentin enacarbil (2011), sofosbuvir (2013), tedizolid phosphate (2014), isavuconazonium (2015), aripiprazole lauroxil (2015), selexipag (2015), latanoprostene bunod (2017), benzhydrocodone (2018), tozinameran (2020) and serdexmethylphenidate (2021).
== Classification ==
Prodrugs can be classified into two major types, based on how the body converts the prodrug into the final active drug form:
Type I prodrugs are bioactivated inside the cells (intracellularly). Examples of these are anti-viral nucleoside analogs that must be phosphorylated and the lipid-lowering statins.
Type II prodrugs are bioactivated outside cells (extracellularly), especially in digestive fluids or in the body's circulatory system, particularly in the blood. Examples of Type II prodrugs are salicin (described above) and certain antibody-, gene- or virus-directed enzyme prodrugs used in chemotherapy or immunotherapy.
Both major types can be further categorized into subtypes, based on factors such as (Type I) whether the intracellular bioactivation location is also the site of therapeutic action, or (Type 2) whether or not bioactivation occurs in the gastrointestinal fluids or in the circulation system.
== Subtypes ==
Type IA prodrugs include many antimicrobial and chemotherapy agents (e.g., 5-flurouracil). Type IB agents rely on metabolic enzymes, especially in hepatic cells, to bioactivate the prodrugs intracellularly to active drugs. Type II prodrugs are bioactivated extracellularly, either in the milieu of GI fluids (Type IIA), within the systemic circulation and/or other extracellular fluid compartments (Type IIB), or near therapeutic target tissues/cells (Type IIC), relying on common enzymes such as esterases and phosphatases or target directed enzymes.
Importantly, prodrugs can belong to multiple subtypes (i.e., Mixed-Type). A Mixed-Type prodrug is one that is bioactivated at multiple sites, either in parallel or sequential steps. For example, a prodrug, which is bioactivated concurrently in both target cells and metabolic tissues, could be designated as a "Type IA/IB" prodrug (e.g., HMG Co-A reductase inhibitors and some chemotherapy agents; note the symbol " / " applied here). When a prodrug is bioactivated sequentially, for example initially in GI fluids then systemically within the target cells, it is designated as a "Type IIA-IA" prodrug (e.g., tenofovir disoproxil; note the symbol " - " applied here). Many antibody- virus- and gene-directed enzyme prodrug therapies (ADEPTs, VDEPTs, GDEPTs) and proposed nanoparticle- or nanocarrier-linked drugs can understandably be Sequential Mixed-Type prodrugs. To differentiate these two Subtypes, the symbol dash " - " is used to designate and to indicate sequential steps of bioactivation, and is meant to distinguish from the symbol slash " / " used for the Parallel Mixed-Type prodrugs.
== See also ==
Precursor (chemistry)
Toxication
Neurotransmitter prodrug
Hypoxia-activated prodrugs
== References ==
== External links ==
Special Issue on Prodrugs: from Design to Applications | Wikipedia/Prodrug |
Chlorine nitrate, with chemical formula ClONO2 is an important atmospheric gas present in the stratosphere. It is an important sink of reactive chlorine and nitrogen, and thus its formation and destruction play an important role in the depletion of ozone.
== Chemical properties ==
It explosively reacts with metals, metal chlorides, alcohols, ethers, and most organic materials. When it is heated to decomposition, it emits toxic fumes of Cl2 and NOx.
== Synthesis and reactions ==
It can be produced by the reaction of dichlorine monoxide and dinitrogen pentoxide at 0 °C:
Cl2O + N2O5 → 2 ClONO2
or by the reaction:
ClF + HNO3 → HF + ClONO2
It can also react with alkenes:
(CH3)2C=CH2 + ClONO2 → O2NOC(CH3)2CH2Cl
Chlorine nitrate reacts with metal chlorides:
4 ClONO2 + TiCl4 → Ti(NO3)4 + 4 Cl2
== References == | Wikipedia/Chlorine_nitrate |
Bismuth oxynitrate is the name applied to a number of compounds that contain Bi3+, nitrate ions and oxide ions and which can be considered as compounds formed from Bi2O3, N2O5 and H2O. Other names for bismuth oxynitrate include bismuth subnitrate and bismuthyl nitrate. In older texts bismuth oxynitrate is often simply described as BiONO3 or basic bismuth nitrate. Bismuth oxynitrate was once called magisterium bismuti or bismutum subnitricum, and was used as a white pigment, in beauty care, and as a gentle disinfectant for internal and external use. It is also used to form Dragendorff's reagent, which is used as a TLC stain.
== Hydrates ==
Bismuth oxynitrate is commercially available as Bi5O(OH)9(NO3)4 (CAS number: 1304-85-4 ) or as BiONO3·H2O (CAS Number: 13595-83-0 ).
Some compounds have been fully characterised with single crystal studies and found to contain the octahedral [Bi6Ox(OH)8−x](10−x)+ cation. There is indirect evidence that either the octahedral cation Bi6O4(OH)6+4 or the octahedral cation Bi6(OH)6+12 is present in aqueous solution following the polymerisation of Bi(H2O)3+8, the Bi3+ ion present in acidic solutions. The ion Bi6O4(OH)6+4 is found in the perchlorate compound Bi6O4(OH)4ClO4·7H2O and is isoelectronic with the octahedral Sn6O4(OH)4 cluster found in the hydrate of tin(II) oxide, 3SnO·H2O. The compounds that contain this are:
Bi6O4(HO)4(NO3)6·H2O (equivalent to BiONO3·1/2H2O; Bi2O3·N2O5·H2O )
Bi6O4(OH)4(NO3)6·4H2O (equivalent to BiONO3·H2O; Bi2O3·N2O5·6H2O )
[Bi6O4(OH)4][Bi6O5(OH)3](NO3)11, which contains two different cations, [Bi6O4(OH)4]6+ and [Bi6O5(OH)3]5+
The compound Bi6O5(OH)3(NO3)5·3H2O (equivalent to 6Bi2O3·5N2O5·9H2O) also contains the octahedral units but this time they are joined to form {[Bi6O5(OH)3]5+}2.
Additionally some oxynitrates have layer structures (a common motif also found in bismuth(III) oxyhalides):
Bi2O2(OH)NO3 (equivalent to BiONO3·1/2H2O) contains "[Bi2O2]2+" layers
Bi5O7NO3, which is isostructural with β-Bi5O7I
== Cluster cation structure ==
The octahedral ion has 6 Bi3+ ions at the corners of an octahedron. There is no covalent bond between the Bi atoms, they are held in position by bridging O2− and OH− anions, one at the centre of each of the eight triangular faces, bridging three Bi ions. The Bi ions are essentially four coordinate and are at the apex of a flat square pyramid. An ab initio theoretical study of the hydration mechanism of Bi3+ and the structure concludes that the lone pairs on the Bi3+ ions are stereochemically active.
== Preparation ==
Bismuth oxynitrates can be prepared from bismuth(III) nitrate. For example, hydrolysis of a solution of bismuth nitrate through the addition of alkali or the reaction of the pentahydrate, BiNO3·5H2O with KOH, or the controlled thermal decomposition of the pentahydrate.
The thermal decomposition of bismuth nitrate pentahydrate proceeds through the following stages:
At pH below 1.0, Bi6O4(OH)4(NO3)6·4H2O (equivalent to BiNO3·H2O) is the first solid product, which when heated produces Bi6H2O(NO3)O4(OH)4 (equivalent to BiNO3.1/2H2O).
Between pH 1.2 and 1.8, further hydrolysis occurs and Bi6O5(OH)3(NO3)5·3H2O is formed.
The final oxynitrate product of thermal dehydration is believed to be Bi5O7NO3, which is isostructural with β–Bi5O7I and has a layer structure. The ultimate stage of thermal decomposition of oxynitrates is bismuth(III) oxide, Bi2O3.
== References == | Wikipedia/Bismuth_oxynitrate |
Cerium nitrate refers to a family of nitrates of cerium in the +3 or +4 oxidation state. Often these compounds contain water, hydroxide, or hydronium ions in addition to cerium and nitrate. Double nitrates of cerium also exist.
== Cerium(III) nitrates ==
Anhydrous cerous nitrate, also called cerium(III) nitrate, is the anhydrous salt with the formula Ce(NO3)3.(CAS number 10108-73-3).
Cerium nitrate hexahydrate, with the formula Ce(NO3)3.6H2O (CAS number 10294-41-4) is the most common nitrate of cerium(III). It is a component in a burn treatment cream that also includes silver sulphadiazine. Concentrations used are 0.5 M for the cerium nitrate. For very serious burns it reduces the death rate. At 150 °C the hexahydrate loses water of crystallization to make a trihydrate, which itself decomposes above 200 °C. Cerous nitrate hexahydrate has pinacoidal triclinic crystals.
Hydronium cerium(III) nitrate hydrate, Ce(NO3)5(H3O)2.H2O is monoclinic with space group P2/c. The diaquapentanitratocerate(III) anion (Ce(NO3)5(H2O)2)2− occurs in several salts. The salts have extreme non-linear optical properties.
== Cerium(IV) nitrates ==
Cerium tetranitrate pentahydrate is prepared by evaporating a solution of ceric nitrate in concentrated nitric acid. It forms orthorhombic crystals with bipyramidal shape. The common crystal face Miller index is {111}, But it can have smaller faces with Miller index {010} and {110}. The density is 2.403 g/cm3. Its optical properties are that it is biaxial with 2V of 34°, and strongly dispersive. On its B and C axes it appears yellow, but orange red on the A axis.
Ceric nitrate is quite soluble in non polar solvents such as ethyl ether. Ether will extract the cerium nitrate from 5N nitric acid. In nitric acid, nitrato ceric acid (H2[Ce(NO3)6] and H[Ce(NO3)5.H2O]) are present. The solubility of this nitrate in non-polar solvents allows the separation of cerium from other rare earths.
Basic cerium(IV) nitrate has the formula Ce(NO3)3.OH.3H2O. It also forms upon evaporation of solutions of cerium(IV) in nitric acid. When this meets ammonia in water solution it reacts to form ceric ammonium nitrate and ceric hydroxide.
Basic dicerium nitrate has the formula Ce2O(NO3)6(H2O)6·2H2O. Again it crystallizes from solutions of cerium(IV) in nitric acid. It crystallises as monoclinic crystals with space group P21lc with unit cell dimensions a=8.723 Å b=8.940 Å c=13.981 Å, β = 94.91°. Each unit cell contains two formula units Ce2O(NO3)6(H2O)3 and Ce2O(NO3)6 form when this basic nitrate is heated slowly to 180 °C in a vacuum.
== Ammonium and alkali metal cerium nitrates ==
The diaquapentanitratocerate(III) anion (Ce(NO3)5(H2O)2)2− occurs in several salts. The salts have extreme non-linear optical properties.
K2Ce(NO3)5 crystals can be grown by evaporating a solution of potassium nitrate, cerous nitrate, and nitric acid. Each cerium atom is surrounded by the oxygen atoms of five bidentate nitrate groups and two water oxygen atoms. It can be grown into optical quality crystals of around 100 cm3 in 12 weeks. Crystals are colourless. The space group of the crystal is Fdd2 and their form is orthorhombic. Potassium cerium nitrate was probably discovered by L. Th. Lange in 1861. However it was only properly described in 1894 by Fock. Even then the amount of water in the substance was wrong and it took till 1911 when Jantsch & Wigdorow correctly stated that there were two water molecules. The non-linear optical effects were found in 1993. For optical applications it is known as KCN.
Diammonium diaquapentanitratocerate dihydrate. Its Raman spectrum has been published. It is quite soluble in water with 100 ml dissolving 235 grams at 9 °C and 817 grams at 65°.
dirubidium diaquapentanitratocerate dihydrate.
dicaesium diaquapentanitratocerate dihydrate, or caesium cerous nitrate Cs2Ce(NO3)5.2H2O forms monoclinic crystals with crystal parameters a/b=1.2052, c/b=0.9816 and β = 103°41'.
dithallium diaquapentanitratocerate dihydrate.
Bis{4-[(4H-1,2,4-triazol-4-yl)iminomethyl]pyridinium} diaquapentanitratocerate. (C8H8N5)2[Ce(NO3)5(H2O)2] is monoclinic with space group C2/c.
== Divalent double nitrates ==
Cerous magnesium nitrate is the first discovered member of a divalent series CeM(II)(NO3)5. This has an extremely low Kapitza resistance to liquid 3He. At the time of discovery it value was only 1% of the previous record holder. Low thermal resistance is important at temperatures below 1K, because there is not much temperature difference to cause a large heat flow rate, and cooling can take an excessive time if there are barriers to heat transfer.
== Other cerous double nitrates ==
Cerous sodium nitrate monohydrate, Na2Ce(NO3)5.H2O has density 2.641 g/cm3. It can be made by boiling the stoichiometric mixture of cerous nitrate, and sodium nitrate in nitric acid, and then evaporating at 40 °C. The crystals are clear rod shaped monoclinic with space group P2/c. Crystal cell sizes are a=21.387 b=7.9328 c=15.184 β=90.657 V=2576 formulas per cell Z=8. The way the components are arranged in the crystal is that there are six nitrates around each cerium atom, however to get to the average of five per cerium, two nitrate groups on each, link the atoms into a chain along the a axis.
There are anhydrous double nitrates such as Ce2Rb3(NO3)9 and Ce2K3(NO3)9. The potassium salt, Ce2K3(NO3)9 can be made by using the water solution of potassium nitrate and cerous nitrate in 3:2 molar ratio, evaporated at 40 °C. The crystals are colourless cubic from space group P4132. Its formula weight is 955.6. Three formulas exist in each unit cell which at 20 °C, has a volume of 2514.1 Å3 and cell side of a=13.597 Å. The density is 2.525 g/cm3. In this compound each cerium atoms is surrounded by twelve oxygen atoms from six nitrate groups. Three of the nitrates form a bridge in each of three dimensions. These bridges form three spirals each at 90° to each other along the crystal axes.
A related series with ratio 1.5 of the monovalent ion to cerium includes 2Ce(NO3)3.3(NH4)NO3.12H2O
A mixed caesium, sodium cerium triple nitrate Cs2NaCe(NO3)6 crystallizes in the cubic system. The unit cell size is 1.1196 nm with volume of 1.4034 nm3 and four molecules per cell.
== Ceric double nitrates ==
The alkali metals form orange-red monoclinic crystals as a double salt with ceric nitrate: M2[Ce(NO3)6] with M=K, Rb, Cs, or [NH4].
Ceric ammonium nitrate contains the icosahedral shaped ion [Ce(NO3)6]2− which has cerium in the +4 oxidation state. It is used as a reagent in oxidimetry.
Ceric potassium nitrate K2[Ce(NO3)6] has two different crystal forms, hexagonal and monoclinic. Slow evaporation and crystallization results in the monoclinic form. But fast crystallization results in a mixture of the two shapes. Both of these forms have six nitrate groups connected via two oxygens each to the cerium [Ce(NO3)6]2−. The substance is made by dissolving ceric hydroxide in nitric acid with the appropriate stoichiometric amount of potassium nitrate. In the hexagonal form the cerium atoms are arranged along a threefold axis. In hexagonal form the potassium ions are surrounded by nine oxygen atoms. These crystals are orange hexagonal shaped plates. Crystal cells contain three molecules, with a volume of 1063.1Å3 and dimensions of a=13.5737Å c=6.6624Å with a density of 2.767 g/cm3.
In the monoclinic form of K2[Ce(NO3)6], the cerium atoms are in a body centred arrangement, with potassium surrounded by ten oxygen atoms. The density is 2.798 g/cm3 with a cell that contains two molecules with volume 700.9Å3 and dimensions a = 12.707Å b = 6.6858Å c = 8.253Å and β = 91.55°.
Ceric potassium nitrate also has a hydrate with 1.5 mols of water.
Ceric rubidium nitrate Rb2[Ce(NO3)6] is reddish yellow.
Ceric caesium nitrate Cs2[Ce(NO3)6] is very insoluble in nitric acid and is bright yellow.
The thallium double salt cannot be produced because the ceric ion oxidizes thallium(I) to thallium(III).
=== Divalent metals ===
Ceric magnesium nitrate Mg[Ce(NO3)6.8H2O]
Ceric zinc nitrate Zn[Ce(NO3)6.8H2O]
Ceric nickel nitrate Ni[Ce(NO3)6.8H2O]
Ceric cobalt nitrate Co[Ce(NO3)6.8H2O]
Ceric manganese nitrate Mn[Ce(NO3)6.8H2O]
== Other compounds ==
[Ce6O(OH)8(NO3)6(H2O)16]·(NO3)2·2H2O is a hexanuclear cerium oxido and hydroxido complex. It can be dehydrated to form [Ce6O(OH)8(NO3)8].
== Proposed application ==
Cerium magnesium nitrate (also known as cerous magnesium nitrate), is a highly paramagnetic salt, and is a possible refrigerant for use in magnetic refrigeration.
== References == | Wikipedia/Cerium_nitrate |
Iodate nitrates are mixed anion compounds that contain both iodate and nitrate anions.
== Giant birefringence ==
Iodate nitrates can have high birefringence. The scandium salt has a giant birefringence of 0.348 at 546 nm. When discovered in 2021 it was a record high birefringence for oxyanion compounds, but it was exceeded by CeF2(SO4) just a month later with a value of 0.361 and sodium hydrogen squarate hydrate, NaHC4O4·H2O with a value of 0.52 at 1064 nm. All of these are beaten by hexagonal boron nitride (h-BN) with birefringence of 0.7 in visible light.
== List ==
== References == | Wikipedia/Iodate_nitrate |
Cobalt nitrate is the inorganic compound with the formula Co(NO3)2.xH2O. It is a cobalt(II) salt. The most common form is the hexahydrate Co(NO3)2·6H2O, which is a red-brown deliquescent salt that is soluble in water and other polar solvents.
== Composition and structures ==
As well as the anhydrous compound Co(NO3)2, several hydrates of cobalt(II) nitrate exist. These hydrates have the chemical formula Co(NO3)2·nH2O, where n = 0, 2, 4, 6.
Anhydrous cobalt(II) nitrate adopts a three-dimensional polymeric network structure, with each cobalt(II) atom approximately octahedrally coordinated by six oxygen atoms, each from a different nitrate ion. Each nitrate ion coordinates to three cobalts. The dihydrate is a two-dimensional polymer, with nitrate bridges between Co(II) centres and hydrogen bonding holding the layers together. The tetrahydrate consists of discrete, octahedral [(H2O)4Co(NO3)2] molecules. The hexahydrate is better described as hexaaquacobalt(II) nitrate, [Co(OH2)6][NO3]2, as it consists of discrete [Co(OH2)6]2+ and [NO3]− ions. Above 55 °C, the hexahydrate converts to the trihydrate and at higher temperatures to the monohydrate.
== Uses and reactions ==
It is commonly reduced to metallic high purity cobalt. It can be absorbed on to various catalyst supports for use in Fischer–Tropsch catalysis. It is used in the preparation of dyes and inks.
Cobalt(II) nitrate is a common starting material for the preparation of coordination complexes such as cobaloximes, carbonatotetraamminecobalt(III), and others.
== Production ==
The hexahydrate is prepared treating metallic cobalt or one of its oxides, hydroxides, or carbonate with nitric acid:
Co + 4 HNO3 + 4 H2O → Co(H2O)6(NO3)2 + 2 NO2
CoO + 2 HNO3 + 5 H2O → Co(H2O)6(NO3)2
CoCO3 + 2 HNO3 + 5 H2O → Co(H2O)6(NO3)2 + CO2
== References == | Wikipedia/Cobalt(II)_nitrate |
Beryllium nitrate is an inorganic compound with the chemical formula Be(NO3)2. It forms a tetrahydrate with the formula [Be(H2O)4](NO3)2.The anhydrous compound, as for many beryllium compounds, is highly covalent. Little of its chemistry is known. Both the anhydrous form and the tetrahydrate are colourless solids that are soluble in water. The anhydrous form produces brown fumes in water, and produces nitrate and nitrite ions when hydrolyzed in sodium hydroxide solution.
== Synthesis and reactions ==
The straw-colored adduct Be(NO3)2(N2O4) forms upon treatment of beryllium chloride with dinitrogen tetroxide in ethyl acetate:
BeCl2 + 3 N2O4 → Be(NO3)2(N2O4) + 2 NOCl
Upon heating, this adduct loses N2O4 and produces colorless Be(NO3)2. Further heating of Be(NO3)2 induces conversion to basic beryllium nitrate (Be4O(NO3)6).
Unlike the basic acetate, with its six lipophilic methyl groups, the basic nitrate is insoluble in most solvents.
The tetrahydrate is produced from the reaction of beryllium oxide or beryllium hydroxide with dilute nitric acid, followed by evaporation of the solution. The heating of the tetrahydrate does not yield the anhydrous form; instead it decomposes at 100 °C to beryllium hydroxide.
== Structure ==
Basic beryllium nitrate adopts a structure akin to that of basic beryllium acetate.
The tetrahydrate consists of isolated [Be(H2O)4]2+ tetrahederons and nitrate anions. The structure of the anhydrous form has not been elucidated yet.
== References == | Wikipedia/Beryllium_nitrate |
Nitrate chlorides are mixed anion compounds that contain both nitrate (NO3−) and chloride (Cl−) ions. Various compounds are known, including amino acid salts, and also complexes from iron group, rare-earth, and actinide metals. Complexes are not usually identified as nitrate chlorides, and would be termed chlorido nitrato complexes.
== Formation ==
Nitrate chloride compounds may be formed by mixing solutions of chloride and nitrate slats, the addition of nitric acid to a chloride salt solution, or the addition of hydrochloric acid to a nitrate solution. Most commonly water is used as a solvent, but other solvents such as methylene dichloride, methanol or ethanol can be used.
== Minerals ==
== List ==
== References == | Wikipedia/Nitrate_chlorides |
Rhenium trioxynitrate, also known as rhenium(VII) trioxide nitrate, is a chemical compound with the formula ReO3NO3. It is a white solid that readily hydrolyzes in moist air.
== Preparation and properties ==
Rhenium trioxynitrate is prepared by the reaction of ReO3Cl (produced by reacting rhenium trioxide and chlorine) and dinitrogen pentoxide:
ReO3Cl + N2O5 → ReO3NO3 + NO2Cl
The ReO3Cl can be replaced with rhenium heptoxide, however, this produces an impure product. This compound reacts with water to produce perrhenic acid and nitric acid.
When heated above 75 °C, it decomposes to rhenium heptoxide, nitrogen dioxide, and oxygen:
4 ReO3NO3 → 2 Re2O7 + 2 NO2 + O2
A graphite intercalation compound can be produced by reacting a mixture of rhenium trioxynitrate and dinitrogen pentoxide with graphite.
== Structure ==
X-ray diffraction and IR spectroscopic evidence rejects the formulations NO2+ReO4– or Re2O7·N2O5, but instead suggests a polymeric structure with a monodentate nitrate ligand.
== References == | Wikipedia/Rhenium_trioxynitrate |
Lutetium(III) nitrate is an inorganic compound, a salt of lutetium and nitric acid with the chemical formula Lu(NO3)3. The compound forms colorless crystals, dissolves in water, and also forms crystalline hydrates. The compound is poisonous.
== Synthesis ==
Dissolving lutetium oxide in nitric acid:
L
u
2
O
3
+
6
H
N
O
3
→
90
o
C
2
L
u
(
N
O
3
)
3
+
3
H
2
O
{\displaystyle {\mathsf {Lu_{2}O_{3}+6HNO_{3}\ {\xrightarrow {90^{o}C}}\ 2Lu(NO_{3})_{3}+3H_{2}O}}}
To obtain anhydrous nitrate, the powdered metal is added to nitrogen dioxide dissolved in ethyl acetate:
L
u
+
3
N
2
O
4
→
77
o
C
L
u
(
N
O
3
)
3
+
3
N
O
{\displaystyle {\mathsf {Lu+3N_{2}O_{4}\ {\xrightarrow {77^{o}C}}\ Lu(NO_{3})_{3}+3NO}}}
== Physical properties ==
Lutetium(III) nitrate forms colorless hygroscopic crystals.
Soluble in water and ethanol.
Forms crystalline hydrates of the composition Lu(NO3)3•nH2O, where n = 3, 4, 5, 6.
== Chemical properties ==
The hydrated lutetium nitrate thermally decomposes to form LuONO3 and decomposes to lutetium oxide upon further heating.
The compound forms ammonium hexafluoroluthenate with ammonium fluoride:
L
u
(
N
O
3
)
3
+
6
N
H
4
F
→
(
N
H
4
)
3
[
L
u
F
6
]
↓
+
3
N
H
4
N
O
3
{\displaystyle {\mathsf {Lu(NO_{3})_{3}+6NH_{4}F\ \xrightarrow {} \ (NH_{4})_{3}[LuF_{6}]\downarrow +3NH_{4}NO_{3}}}}
== Applications ==
Lutetium(III) nitrate is used to obtain metallic lutetium and also as a chemical reagent.
It is used as a component of materials for the production of laser crystals.
== References == | Wikipedia/Lutetium(III)_nitrate |
Mercury(I) nitrate is an inorganic compound, a salt of mercury and nitric acid with the formula Hg2(NO3)2. A yellow solid, the compound is used as a precursor to other Hg22+ complexes. The structure of the hydrate has been determined by X-ray crystallography. It consists of a [H2O-Hg-Hg-OH2]2+ center, with a Hg-Hg distance of 254 pm.
It was first mentioned by Indian chemist Acharya Prafulla Chandra Ray in 1896.
== Reactions ==
Mercury(I) nitrate is formed when elemental mercury is combined with dilute nitric acid (concentrated nitric acid will yield mercury(II) nitrate). Mercury(I) nitrate is a reducing agent which is oxidized upon contact with air.
Mercuric(II) nitrate reacts with elemental mercury(0) to form mercurous(I) nitrate (comproportionation reaction):
Hg(NO3)2 + Hg ⇌ Hg2(NO3)2
Solutions of mercury(I) nitrate are acidic due to slow reaction with water:
Hg2(NO3)2 + H2O ⇌ Hg2(NO3)(OH) + HNO3
Hg2(NO3)(OH) forms a yellow precipitate.
If the solution is boiled, or exposed to light, mercury(I) nitrate undergoes a disproportionation reaction yielding elemental mercury and mercury(II) nitrate:
Hg2(NO3)2 ⇌ Hg + Hg(NO3)2
These reactions are reversible; the nitric acid formed can redissolve the basic salt.
== References == | Wikipedia/Mercury(I)_nitrate |
Diethylene glycol dinitrate (DEGDN) is an explosive nitrated alcohol ester with the formula C4H8N2O7. It is commonly used as a plasticizer in propellant or explosive formulations. While chemically similar to numerous other high explosives, pure diethylene glycol dinitrate is difficult to ignite. Ignition typically requires localized heating to the decomposition point unless the DEGDN is first atomized. It is sensitive to detonation by impact but not due to friction.
== Preparation and uses ==
Diethylene glycol dinitrate can be made by nitration of diethylene glycol with nitric acid in presence of a dehydrating agent like concentrated sulfuric acid.
== Toxicity ==
If ingested, like nitroglycerine, it rapidly causes vasodilation through the release of nitric oxide, a physiological signaling molecule that relaxes vascular smooth muscle which leads to a rapid loss in blood pressure. Other acute effects include convulsions and loss of consciousness. Its median lethal dose (LD50) is 650 mg/kg in guinea pigs.
== Uses ==
DEGDN can be mixed with nitrocellulose or nitroglycol to form a colloid, which is used in smokeless powder for artillery and rocket propellant. During World War II, the Kriegsmarine frequently used this mixture in their artillery.
Triethylene glycol dinitrate, diethylene glycol dinitrate, and trimethylolethane trinitrate can be used as less-sensitive as replacements for nitroglycerin in propellants.
== See also ==
Triethylene glycol dinitrate
Ethylene glycol dinitrate
TNT equivalent
RE factor
== References ==
W. H. Rinkenbach, Industrial Engineering Chemistry v19 p925 (1927) Note: the present author has transliterated some terminology and notation in line with modern practice.
Military applications referenced in Encyclopedia of Weapons of World War 2; Gen. Ed. Chris Bishop, c.2003 Friedman/Fairfax NYNY, ISBN 1-58663-762-2 | Wikipedia/Diethylene_glycol_dinitrate |
Silver nitrate is an inorganic compound with chemical formula AgNO3. It is a versatile precursor to many other silver compounds, such as those used in photography. It is far less sensitive to light than the halides. It was once called lunar caustic because silver was called luna by ancient alchemists who associated silver with the moon. In solid silver nitrate, the silver ions are three-coordinated in a trigonal planar arrangement.
== Synthesis and structure ==
Albertus Magnus, in the 13th century, documented the ability of nitric acid to separate gold and silver by dissolving the silver. Indeed silver nitrate can be prepared by dissolving silver in nitric acid followed by evaporation of the solution. The stoichiometry of the reaction depends upon the concentration of nitric acid used.
3 Ag + 4 HNO3 (cold and diluted) → 3 AgNO3 + 2 H2O + NO
Ag + 2 HNO3 (hot and concentrated) → AgNO3 + H2O + NO2
The structure of silver nitrate has been examined by X-ray crystallography several times. In the common orthorhombic form stable at ordinary temperature and pressure, the silver atoms form pairs with Ag---Ag contacts of 3.227 Å. Each Ag+ center is bonded to six oxygen centers of both uni- and bidentate nitrate ligands. The Ag-O distances range from 2.384 to 2.702 Å.
== Reactions ==
A typical reaction with silver nitrate is to suspend a rod of copper in a solution of silver nitrate and leave it for a few hours. The silver nitrate reacts with copper to form hairlike crystals of silver metal and a blue solution of copper nitrate:
2 AgNO3 + Cu → Cu(NO3)2 + 2 Ag
Silver nitrate decomposes when heated:
2 AgNO3(l) → 2 Ag(s) + O2(g) + 2 NO2(g)
Qualitatively, decomposition is negligible below the melting point, but becomes appreciable around 250 °C and fully decomposes at 440 °C.
Most metal nitrates thermally decompose to the respective oxides, but silver oxide decomposes at a lower temperature than silver nitrate, so the decomposition of silver nitrate yields elemental silver instead.
== Uses ==
=== Precursor to other silver compounds ===
Silver nitrate is the least expensive salt of silver; it offers several other advantages as well. It is non-hygroscopic, in contrast to silver fluoroborate and silver perchlorate. In addition, it is relatively stable to light, and it dissolves in numerous solvents, including water. The nitrate can be easily replaced by other ligands, rendering AgNO3 versatile. Treatment with solutions of halide ions gives a precipitate of AgX (X = Cl, Br, I). When making photographic film, silver nitrate is treated with halide salts of sodium or potassium to form insoluble silver halide in situ in photographic gelatin, which is then applied to strips of tri-acetate or polyester. Similarly, silver nitrate is used to prepare some silver-based explosives, such as the fulminate, azide, or acetylide, through a precipitation reaction.
Treatment of silver nitrate with base gives dark grey silver oxide:
2 AgNO3 + 2 NaOH → Ag2O + 2 NaNO3 + H2O
=== Halide abstraction ===
The silver cation, Ag+, reacts quickly with halide sources to produce the insoluble silver halide, which is a cream precipitate if Br− is used, a white precipitate if Cl− is used and a yellow precipitate if I− is used. This reaction is commonly used in inorganic chemistry to abstract halides:
Ag+(aq) + X−(aq) → AgX(s)
where X− = Cl−, Br−, or I−.
Other silver salts with non-coordinating anions, namely silver tetrafluoroborate and silver hexafluorophosphate are used for more demanding applications.
Similarly, this reaction is used in analytical chemistry to confirm the presence of chloride, bromide, or iodide ions. Samples are typically acidified with dilute nitric acid to remove interfering ions, e.g. carbonate ions and sulfide ions. This step avoids confusion of silver sulfide or silver carbonate precipitates with that of silver halides. The color of precipitate varies with the halide: white (silver chloride), pale yellow/cream (silver bromide), yellow (silver iodide). AgBr and especially AgI photo-decompose to the metal, as evidenced by a grayish color on exposed samples.
The same reaction was used on steamships in order to determine whether or not boiler feedwater had been contaminated with seawater. It is still used to determine if moisture on formerly dry cargo is a result of condensation from humid air, or from seawater leaking through the hull.
=== Organic synthesis ===
Silver nitrate is used in many ways in organic synthesis, e.g. for deprotection and oxidations. Ag+ binds alkenes reversibly, and silver nitrate has been used to separate mixtures of alkenes by selective absorption. The resulting adduct can be decomposed with ammonia to release the free alkene. Silver nitrate is highly soluble in water but is poorly soluble in most organic solvents, except acetonitrile (111.8 g/100 g, 25 °C).
=== Biology ===
In histology, silver nitrate is used for silver staining, for demonstrating reticular fibers, proteins and nucleic acids. For this reason it is also used to demonstrate proteins in PAGE gels. It can be used as a stain in scanning electron microscopy.
Cut flower stems can be placed in a silver nitrate solution, which prevents the production of ethylene. This delays ageing of the flower.
=== Indelible ink ===
Silver nitrate produces long-lasting stain when applied to skin and is one of indelible ink’s ingredients. An electoral stain makes use of this to mark a finger of people who have voted in an election, allowing easy identification to prevent double-voting.
In addition to staining skin, silver nitrate has a history of use in stained glass. In the 14th century, artists began using a "silver stain" (also known as a yellow stain) made from silver nitrate to create a yellow effect on clear glass. The stain would produce a stable color that could range from pale lemon to deep orange or gold. Silver stain was often used with glass paint, and was applied to the opposite side of the glass as the paint. It was also used to create a mosaic effect by reducing the number of pieces of glass in a window. Despite the age of the technique, this process of creating stained glass remains almost entirely unchanged.
== Medicine ==
Silver salts have antiseptic properties. In 1881 Credé introduced a method known as Credé's prophylaxis, which used of dilute (2%) solutions of silver nitrate in newborn babies' eyes at birth to prevent contraction of gonorrhea from the mother, which could cause blindness via ophthalmia neonatorum. (Modern antibiotics are now used instead).
Fused silver nitrate, shaped into sticks, was traditionally called "lunar caustic". It is used as a cauterizing agent, for example to remove granulation tissue around a stoma. General Sir James Abbott noted in his journals that in India in 1827 it was infused by a British surgeon into wounds in his arm resulting from the bite of a mad dog to cauterize the wounds and prevent the onset of rabies.
Silver nitrate is used to cauterize superficial blood vessels in the nose to help prevent nosebleeds.
Dentists sometimes use silver nitrate-infused swabs to heal oral ulcers. Silver nitrate is used by some podiatrists to kill cells located in the nail bed.
The Canadian physician C. A. Douglas Ringrose researched the use of silver nitrate for sterilization procedures, believing that silver nitrate could be used to block and corrode the fallopian tubes. The technique was ineffective.
=== Disinfection ===
Much research has been done in evaluating the ability of the silver ion at inactivating Escherichia coli, a microorganism commonly used as an indicator for fecal contamination and as a surrogate for pathogens in drinking water treatment. Concentrations of silver nitrate evaluated in inactivation experiments range from 10–200 micrograms per liter as Ag+.
Silver's antimicrobial activity saw many applications prior to the discovery of modern antibiotics, when it fell into near disuse. Its association with argyria made consumers wary and led them to turn away from it when given an alternative.
=== Against warts ===
Repeated daily application of silver nitrate can induce adequate destruction of cutaneous warts, but occasionally pigmented scars may develop. In a placebo-controlled study of 70 patients, silver nitrate given over nine days resulted in clearance of all warts in 43% and improvement in warts in 26% one month after treatment compared to 11% and 14%, respectively, in the placebo group.
== Safety ==
As an oxidant, silver nitrate should be properly stored away from organic compounds. It reacts explosively with ethanol. Despite its common usage in extremely low concentrations to prevent gonorrhea and control nosebleeds, silver nitrate is still very toxic and corrosive. Brief exposure will not produce any immediate side effects other than the purple, brown or black stains on the skin, but upon constant exposure to high concentrations, side effects will be noticeable, which include burns. Long-term exposure may cause eye damage. Silver nitrate is known to be a skin and eye irritant. Silver nitrate has not been thoroughly investigated for potential carcinogenic effect.
Silver nitrate is currently unregulated in water sources by the United States Environmental Protection Agency. However, if more than 1 gram of silver is accumulated in the body, a condition called argyria may develop. Argyria is a permanent cosmetic condition in which the skin and internal organs turn a blue-gray color. The United States Environmental Protection Agency used to have a maximum contaminant limit for silver in water until 1990, when it was determined that argyria did not impact the function of any affected organs despite the discolouration. Argyria is more often associated with the consumption of colloidal silver solutions rather than with silver nitrate, since it is only used at extremely low concentrations to disinfect the water. However, it is still important to be wary before ingesting any sort of silver-ion solution.
== References ==
== External links ==
International Chemical Safety Card 1116
NIOSH Pocket Guide to Chemical Hazards
History of Kodak: About Film and Imaging
https://www.cofesilver.com/en/silver_bar :silver bar explanation. pricing investing | Wikipedia/Silver_nitrate |
Polonium tetranitrate is an inorganic compound, a salt of polonium and nitric acid with the chemical formula Po(NO3)4. The compound is radioactive, forms white crystals.
== Synthesis ==
Dissolution of metallic polonium in concentrated nitric acid:
P
o
+
8
H
N
O
3
→
P
o
(
N
O
3
)
4
+
4
N
O
2
↑
+
4
H
2
O
{\displaystyle {\mathsf {Po+8HNO_{3}\ {\xrightarrow {}}\ Po(NO_{3})_{4}+4NO_{2}\uparrow +4H_{2}O}}}
== Physical properties ==
Polonium(IV) nitrate forms white or colorless crystals. It dissolves in water with hydrolysis.
== Chemical properties ==
It disproportionates in aqueous weakly acidic nitric acid solutions:
2
P
o
(
N
O
3
)
4
+
2
H
2
O
→
P
o
O
2
(
N
O
3
)
2
↓
+
P
o
2
+
+
2
N
O
3
−
+
4
H
N
O
3
{\displaystyle {\mathsf {2Po(NO_{3})_{4}+2H_{2}O\ \xrightarrow {} \ PoO_{2}(NO_{3})_{2}\downarrow +Po^{2+}+2NO_{3}^{-}+4HNO_{3}}}}
The polonium(II) ion (Po2+) is then oxidized by nitric acid to polonium(IV).
== References == | Wikipedia/Polonium_tetranitrate |
Uranyl nitrate is a water-soluble yellow uranium salt with the formula UO2(NO3)2 · n H2O. The hexa-, tri-, and dihydrates are known. The compound is mainly of interest because it is an intermediate in the preparation of nuclear fuels. In the nuclear industry, it is commonly referred to as yellow salt.
Uranyl nitrate can be prepared by reaction of uranium salts with nitric acid. It is soluble in water, ethanol, and acetone. As determined by neutron diffraction, the uranyl center is characteristically linear with short U=O distances. In the equatorial plane of the complex are six U-O bonds to bidentate nitrate and two water ligands. At 245 pm, these U-O bonds are much longer than the U=O bonds of the uranyl center.
== Uses ==
=== Processing of nuclear fuels ===
Uranyl nitrate is important for nuclear reprocessing. It is the compound of uranium that results from dissolving the decladded spent nuclear fuel rods or yellowcake in nitric acid, for further separation and preparation of uranium hexafluoride for isotope separation for preparing of enriched uranium. A special feature of uranyl nitrate is its solubility in tributyl phosphate (PO(OC4H9)3), which allows uranium to be extracted from the nitric acid solution. Its high solubility is attributed to the formation of the lipophilic adduct UO2(NO3)2(OP(OBu)3)2.
=== Archaic photography ===
During the first half of the 19th century, many photosensitive metal salts had been identified as candidates for photographic processes, among them uranyl nitrate. The prints thus produced were called uranium prints or uranotypes.
The first uranium printing processes were invented by Scotsman J. Charles Burnett between 1855 and 1857, and used this compound as the sensitive salt. Burnett authored a 1858 article comparing "Printing by the Salts of the Uranic and Ferric Oxides"
The process employs the ability of the uranyl ion to pick up two electrons and reduce to the lower oxidation state of uranium(IV) under ultraviolet light.
Uranotypes can vary from print to print from a more neutral, brown russet to strong Bartolozzi red, with a very long tone grade. Surviving prints are slightly radioactive, a property which serves as a means of non-destructively identifying them.
Several other more elaborate photographic processes employing the compound appeared and vanished during the second half of the 19th century with names like Wothlytype, Mercuro-Uranotype and the Auro-Uranium process. Uranium papers were manufactured commercially at least until the end of the 19th century, vanishing due to the superior sensitivity and practical advantages of silver halides. From the 1930s through the 1950s Kodak Books described a uranium toner (Kodak T-9) using uranium nitrate hexahydrate.
=== Stain for microscopy ===
Along with uranyl acetate it is used as a negative stain for viruses in electron microscopy; in tissue samples it stabilizes nucleic acids and cell membranes.
=== As a reagent ===
Uranyl nitrates are common starting materials for the synthesis of other uranyl compounds because the nitrate ligand is easily replaced by other anions. It reacts with oxalate to give uranyl oxalate. Treatment with hydrochloric acid gives uranyl chloride.
== Health and environmental issues ==
Uranyl nitrate is an oxidizing and highly toxic compound. When ingested, it causes severe chronic kidney disease and acute tubular necrosis and is a lymphocyte mitogen. Target organs include the kidneys, liver, lungs and brain. It also represents a severe fire and explosion risk when heated or subjected to shock in contact with oxidizable substances.
== References ==
== External links ==
URANIUM DAYS: Notes On Uranium Photography (2007 archive from archive.org)
Chemical Database – Uranyl nitrate, solid | Wikipedia/Uranyl_nitrate |
Copper(I) nitrate is a proposed inorganic compound with formula of CuNO3. It has not been characterized by X-ray crystallography. It is the focus of one publication, which describes unsuccessful efforts to isolate the compound. Another nonexistent simple copper(I) compound derived from an oxyanion is cuprous perchlorate. On the other hand, cuprous sulfate is known.
== Derivatives ==
The nitrate salt of the acetonitrile complex, i.e., [Cu(MeCN)4]NO3, is generated by the reaction of silver nitrate with a suspension of copper metal in acetonitrile.
Cu + AgNO3 + 4 CH3CN → [Cu(CH3CN)4]NO3 + Ag
Tertiary phosphine complexes of the type [Cu(P(C6H5)3)3]NO3 are prepared by the reduction of copper(II) nitrate by the phosphine.
== References == | Wikipedia/Copper(I)_nitrate |
Erbium(III) nitrate is an inorganic compound, a salt of erbium and nitric acid with the chemical formula Er(NO3)3. The compound forms pink crystals, readily soluble in water, also forms crystalline hydrates.
== Synthesis ==
Dissolving metallic erbium in nitric acid:
Er + 6 HNO3 → Er(NO3)3 + 3 NO2 + 3 H2O ↑
Dissolving erbium oxide or hydroxide in nitric acid:
Er(OH)3 + 3 HNO3 → Er(NO3)3 + 3 H2O ↑
Reaction of nitrogen dioxide with metallic erbium:
Er + 3 N2O4 → Er(NO3)3 + 3 NO ↑
== Physical properties ==
Erbium(III) nitrate forms pink hygroscopic crystals.
Forms crystalline hydrates of the composition Er(NO3)3·5H2O.
Both erbium(III) nitrate and its crystalline hydrate decompose on heating.
Dissolves in water and EtOH.
== Chemical properties ==
The hydrated erbium nitrate thermally decomposed to form ErONO3 and then to erbium oxide.
== Applications ==
It is used to obtain metallic erbium and is also used as a chemical reagent.
== References == | Wikipedia/Erbium(III)_nitrate |
Lithium nitrate is an inorganic compound with the formula LiNO3. It is the lithium salt of nitric acid (an alkali metal nitrate). The salt is deliquescent, absorbing water to form the hydrated form, lithium nitrate trihydrate. Its eutectics are of interest for heat transfer fluids.
It is made by treating lithium carbonate or lithium hydroxide with nitric acid.
== Uses ==
This deliquescent colourless salt is an oxidizing agent used in the manufacture of red-colored fireworks and flares.
=== Thermal storage ===
The hydrated form, lithium nitrate trihydrate, has an extremely high specific heat of fusion, 287±7 J/g, and hence can be used for thermal energy storage at its melt temperature of 303.3 K.
Lithium nitrate has been proposed as a medium to store heat collected from the sun for cooking. A Fresnel lens would be used to melt solid lithium nitrate, which would then function as a "solar battery", allowing heat to be redistributed later by convection.
== Synthesis ==
Lithium nitrate can be synthesized by reacting nitric acid and lithium carbonate.
Li2CO3 + 2 HNO3 → 2 LiNO3 + H2O + CO2
Generally when forming LiNO3, a pH indicator is used to determine when all of the acid has been neutralized. However, this neutralization can also be recognized with the loss of carbon dioxide production. In order to rid the final product of excess water, the sample is heated.
== Toxicity ==
Lithium nitrate can be toxic to the body when ingested by targeting the central nervous system, thyroids, kidneys, and cardio-vascular system.
When exposed to the skin, eyes, and mucous membranes, lithium nitrate can cause irritation to these areas.
== Further reading ==
Berchiesi, Gianfrancesco; Vitali, Giovanni; Amico, Antonio (1985). "Transport properties of lithium nitrate and calcium nitrate binary solutions in molten acetamide". Journal of Chemical & Engineering Data. 30 (2): 208–9. doi:10.1021/je00040a023.
Kelly, Michael T; Tuan, Christopher Y (2006). "A Case Study Evaluating the Use of Lithium Nitrate to Arrest Alkali-Silica Reaction in an Existing Concrete Pavement". Airfield and Highway Pavement. pp. 625–35. doi:10.1061/40838(191)53. ISBN 978-0-7844-0838-4.
Muniz-Miranda, Francesco; Pagliai, Marco; Cardini, Gianni; Righini, Roberto (2012). "Bifurcated Hydrogen Bond in Lithium Nitrate Trihydrate Probed by ab Initio Molecular Dynamics". The Journal of Physical Chemistry A. 116 (9): 2147–53. Bibcode:2012JPCA..116.2147M. doi:10.1021/jp2120115. PMID 22309150.
Ruiz, María L; Lick, Ileana D; Leguizamón Aparicio, María S; Ponzi, Marta I; Rodriguez-Castellón, Enrique; Ponzi, Esther N (2012). "NO Influence on Catalytic Soot Combustion: Lithium Nitrate and Gold Catalysts". Industrial & Engineering Chemistry Research. 51 (3): 1150–7. doi:10.1021/ie201295s.
== References ==
== External links ==
Hazardous Chemical Database | Wikipedia/Lithium_nitrate |
Chromium(III) nitrate describes several inorganic compounds consisting of chromium, nitrate and varying amounts of water. Most common is the dark violet hygroscopic solid. An anhydrous green form is also known. Chromium(III) nitrate compounds are of a limited commercial importance, finding some applications in the dyeing industry. It is common in academic laboratories for the synthesis of chromium coordination complexes.
== Structure ==
The relatively complicated formula - [Cr(H2O)6](NO3)3•3H2O - betray a simple structure of this material. The chromium centers are bound to six aquo ligands, and the remaining volume of the solid is occupied by three nitrate anions and three molecules of water of crystallization.
== Properties and preparation ==
The anhydrous salt forms green crystals and is very soluble in water (in contrast to anhydrous chromium(III) chloride which dissolves very slowly except under special conditions). At 100 °C it decomposes. The red-violet hydrate is highly soluble in water. Chromium nitrate is used in the production of alkali metal-free catalysts and in pickling.
Chromium nitrate can be prepared by dissolving chromium oxide in nitric acid.
== References == | Wikipedia/Chromium(III)_nitrate |
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