VG (nerve agent)
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| Names | |
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| Preferred IUPAC name
S-[2-(Diethylamino)ethyl] O,O-diethyl phosphorothioate [4] | |
Other names
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| Identifiers | |
3D model (JSmol)
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| 17856074 | |
| ChemSpider | |
| MeSH | C003415 |
PubChem CID
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| RTECS number |
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| UNII | |
| UN number | 3018 |
CompTox Dashboard (EPA)
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| Properties | |
| C10H24NO3PS1 [3] | |
| Molar mass | 269.341 g/mol [3] |
| Appearance | Colourless liquid [3] |
| Density | 1.070±0.06 g/cm3(Predicted) [3] |
| Melting point | 25[3] °C (77 °F; 298 K) |
| Boiling point | 110 °C (230 °F; 383 K) at 0.2 mmHg [3] |
| 33.92 mg/L [5] | |
| log P | 3.24250 [6] |
| Vapor pressure | 0.01 mmHg at 80°C [1] |
| Acidity (pKa) | 9.39±0.25(Predicted) [3] |
| Structure | |
| Pointgroup C1 | |
| Distorted tetrahedral | |
| Hazards | |
| GHS labelling: | |
| toxic [7] | |
| Danger[7] | |
| H300, H320 [7] | |
| P280, P284, P405, P403, H373, H271 [7] | |
| NFPA 704 (fire diamond) | |
| Flash point | 144.3°C [6] |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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| Safety data sheet (SDS) | Chemwatch |
| Related compounds | |
Related Organophosphates
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Amiton (IUPAC name: O,O-diethyl S-[2-(diethylamino)ethyl] phosphorothioate) (also called VG or Tetram) is a "V-series" nerve agent chemically similar to the better-known VX nerve agent. Tetram is the common Russian name for the substance. Amiton was the trade name for the substance when it was marketed as an insecticide by ICI in the mid-1950s.
Like all V-series nerve agents, both VX and Amiton disrupt the breakdown of acetylcholine, a neurotransmitter responsible for muscle contraction. When its breakdown is inhibited, muscles remain continuously stimulated, leading to severe physiological effects such as paralysis and respiratory failure.[9] Amiton has a toxicity of about 1/10 of VX similar to sarin. [10]
History
[edit]Amiton was first synthesized as an insecticide in the 1950s. It was introduced commercially as a miticide, but due to its unexpectedly high toxicity in humans, its persistence in the environment, and its ability to enter the bloodstream through skin contact, it was withdrawn from the market. [11]
During the early 1950s, multiple chemical companies researching organophosphorus insecticides independently discovered their high toxicity.[12] In 1952, Dr. Ranajit Ghosh, a chemist at Imperial Chemical Industries (ICI), investigated organophosphate esters of substituted aminoethanethiols as potential pesticides. Like the German discovery of G-series nerve agents in the 1930s, Ghosh found that these compounds inhibited cholinesterase, making them highly effective against pests. One such compound, Amiton, was identified as particularly effective against mites. In 1955, Ghosh and J. F. Newman published a paper on its effectiveness[12], and Amiton was introduced to the market as an insecticide in 1954. However, due to its extreme toxicity, it was soon withdrawn from agricultural use. [13][14][15]
Before Amiton’s commercial release, the British government had already taken notice of the extreme toxicity of these organophosphate compounds. Some were sent to Porton Down, Britain’s chemical weapons research facility, for evaluation. This led to the identification of a new class of nerve agents, later named V (venomous) agents. While Britain officially renounced chemical and biological weapons in 1956, they later traded their research on amiton technology with the United States in 1958 in exchange for information on thermonuclear weapons. The U.S. continued research into the V-series agents, leading to the mass production of VX—a chemically similar but far more toxic compound—in 1961. After this, amiton was no longer pursued for chemical warfare or as a pesticide.[14][15][16]
Although VX has been used as a chemical weapon, amiton has not. The Chemical Weapons Convention (CWC) classifies VX as a Schedule 1 chemical and amiton as a Schedule 2 chemical.[17] While Schedule 2 chemicals are subject to fewer restrictions than Schedule 1 chemicals, they are still highly regulated. CWC member states are required to submit annual reports detailing the amounts of Schedule 2 chemicals they synthesize, process, consume, import, and export. Additionally, any trade involving these chemicals must specify the recipient country, and exports to non-CWC member states are strictly prohibited. Furthermore, any facility that produces, processes, or consumes more than 100 kg of amiton or any other Schedule 2 chemical per year must be declared to the Organisation for the Prohibition of Chemical Weapons (OPCW) and is subject to international inspection. These regulations ensure strict monitoring and prevent the misuse of Schedule 2 chemicals while allowing limited, legitimate industrial and research applications.[18]
It is thought that North Korea may have military stockpiles of this chemical .[19]
It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[20]
Structure and Reactivity
[edit]Amiton is an organophosphate, specifically an organothiophosphate, with two ethyl groups bonded to the oxygen atoms and a triethylamine side group. This structure allows the molecule to undergo several chemical reactions.
Hydrolysis
[edit]Like most organophosphorus, Amiton can undergo hydrolysis upon contact with water[21]. This reaction will primarily result in the release of the sulfur containing side group, also the oxygen-linked ethyl groups can be released in small quantities[22][23]. However, both of hydrolysis reactions occur relatively slowly[21]. The hydrolysed products may be less toxic, but they can still pose health risks[21].
Thiono-thiol Isomerization
[edit]Amiton can also undergo thiono-thiol isomerization[21]. In this reaction, the P=O double bond converts into a single bond, while the single bonded sulfur forms a double bond with the phosphorus[24]. This reaction can potentially lead to the formation of toxic products[21].
Decomposition
[edit]Amiton undergoes thermal decomposition when heated. Like other organothiophosphates, it breaks down, forming sulfur oxides (SOₓ), nitrogen oxides (NOₓ), and phosphorus oxides (POₓ)[21]. These decomposition products are highly toxic and should not be inhaled[25].
Synthesis
[edit]Synthesis of Amiton
[edit]Amiton, like most organothiophosphates, can be synthesized by reacting a dialkylchlorothiophosphate with an amino thioalcohol[26]. Specifically O,O-diethyl phosphorochloridothioate and 2-diethylaminoethanethiol are used to form amiton. In this reaction it is important to know if a thiono of thiol dialkylchlorothiophosphate is used. When using the thoino variant it is important to closely monitor the reaction temperature to synthesize the desired dialkylchlorothiophosphate[26]. Wereas, for a thoil starting product, high reaction temperatures do not affect the type of dialkylchlorothiophosphate synthesized[26].
Synthesis of Dialkylchlorothiophosphates
[edit]To synthesize a dialkylchlorothiophosphate, PCl3 (phosphorus trichloride) is mixed with alcohols or sulfides[26]. The Regel method is the most effective approach for this synthesis, as it results into the highest yield[26].
Synthesis of Amino Thioalcohols
[edit]To synthesize amino thioalcohol, such as 2-diethylaminoethanethiol, an amine is first alkylated twice with alkyl halides, such as bromoethane, to form a secondary amine[26]. This secondary amine than reacts with ethylene sulfide, resulting in the formation of 2-diethylaminoethanol[26].
Availability and Use
[edit]Availability
[edit]Amiton is no longer sold because it is very toxic, and its use is controlled around the world by treaties regarding chemical arms. To discourage abuse, manufacturing, allocation, and ownership are firmly regulated.[27].
Use and Efficacy
[edit]Amiton, from the beginning, was made with its strong action against insects, and it became highly effective for pests. However, the big bad effects on unplanned organisms, most notably humans, quickly turned out to be more vital than its purpose, so its use as a bug killer was discontinued. Ongoing research into the use of Amiton continues.[28].Ongoing research focuses on enhancing its formulations to improve efficacy while reducing exposure risks. Additionally, studies are investigating its potential applications in biochemical research, particularly in enzyme inhibition mechanisms.[29]
Adverse Effects and Toxicity
[edit]Amiton is very toxic since it permanently stops acetylcholinesterase from working, which results in neuromuscular junctions having too much acetylcholine. A brief exposure could produce many severe conditions like multiple muscle spasms, many breathing problems, and particular nerve harm. Amiton goes into skin and mucous membranes easily. Therefore, contact raises the chance of unintended poisoning with it. The meaningful health risks with Amiton exposure contributed considerably, as well as substantially, to its reclassification as a nerve agent in addition to subsequent removal from agricultural use. [30]. This high toxicity and rapid absorption capability contributed significantly to the withdrawal of Amiton from agricultural use and its subsequent classification as a nerve agent[31].
Metabolism
[edit]Because of Amiton’s high toxicity, not much biotransformation is observed. In most cases, the victim is dead before biotransformation occurred. Therefore, biotransformation of amiton is not important and little to no research is done on this topic. However, there are a few pathways known to metabolize amiton.
Metabolism occurs via oxidation by cytochrome p450, hydrolysis by esterases and addition of glutathione by glutathionetransferase (GST)[32]. Oxidation of amiton yields the nontoxic diethylphosphate (DEP). Depending on which bond is broken during the hydrolysis, the resulting compound is toxic or not. When the P-S bond is broken, the nontoxic DEP is formed, but when a P-O bond is broken a toxic metabolite is formed[33]. Conjugation of amiton or its metabolites to glutathione yields products with lower/no toxicity. These products are eliminated via bile or renal excretion[32].
Mechanism of Action
[edit]Inhibition of Acetylcholinesterase
[edit]Organophosphate like Amiton inhibit the acetylcholinesterase enzyme which breaks down acetylcholine into acetate and choline. The active site of the enzyme contains two important regions: The anionic site and the esteratic site. The anionic site binds the positive quaternary amine of the substrate and the esteratic part binds, as the name suggests, the ester part of the acetylcholine. Three key amino acid residues: Serine, glutamate and histidine facilitate the breakdown of acetylcholine. The inhibition works by the irreversible phosphorylation of the serine present in the active site[34]. This blocks the enzyme from functioning and acetylcholine builds up in the synapses, resulting in continuous activation of the acetylcholine receptors.
Symptoms
[edit]The continuous activation of the acetylcholine receptors leads to various symptoms. The first symptoms shown after exposure to amiton are a runny nose (rhinorrhea), contraction of the pupils (Miosis) and tightness in the chest with shortness of breath[35]. After this the exposed person loses control of their muscles causing involuntary excretions like urination and vomiting, muscle convulsions. This is followed by flaccid paralysis resulting in death by suffocation due to the inability to move the diaphragm. A common mnemonic used to describe the symptoms of organophosphate poisoning is SLUDGE: Salivation, lacrimation, urination, defecation, gastrointestinal distress and emesis. Symptoms often appear within minutes to hours, but can be delayed when exposure is limited and the person is left untreated.
Treatment
[edit]Amiton poisoning can be treated with symptomatic and causal drugs. Symptomatic drugs are used to treat the symptoms. Anticonvulsant like diazepam are used to reduce the convulsions[36], and parasympatholytic like atropine are used to reduce the effects of the accumulated acetylcholine[37]. Causal drugs treat the causes of the problem, in this case the inhibited acetylcholinesterase. With the use of oxime compounds, the phosphor group can be removed from the enzyme, activating it again[38][39]. The administration of these drugs should be done quickly after poisoning, otherwise the function of the enzyme cannot be restored[40].
Toxicology Data
[edit]The median lethal dose (LD50) was tested in rats through oral, intraperitoneal, and subcutaneous administration. The oral LD50 for rats is 3,300 mg/kg, which equates to an estimated oral LD50 of 231 mg for a 70 kg human. The intraperitoneal LD50 in rats is 0,600 mg/kg, corresponding to 42 mg for a 70 kg human, while the subcutaneous LD50 is 0,150 mg/kg, translating to 10.5 mg for a 70 kg human.[41][42]
Acknowledgements
[edit]We acknowledge the use of AI assistance, specifically ChatGPT, to help paraphrase and refine portions of this text. While the final content was reviewed and edited by our team, AI was utilized to enhance clarity and readability.
References
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