VG (nerve agent)
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Names | |
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Preferred IUPAC name
S-[2-(Diethylamino)ethyl] O,O-diethyl phosphorothioate | |
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 | |
C10H24NO3PS | |
Molar mass | 269.34 g·mol−1 |
Appearance | Colourless liquid |
Density | 1.070±0.06 g/cm3(Predicted) |
Melting point | 25 °C (77 °F; 298 K) |
Boiling point | 110 °C (230 °F; 383 K) at 0.2 mmHg |
33.92 mg/L | |
log P | 3.24250 |
Vapor pressure | 0.01 mmHg at 80 °C |
Acidity (pKa) | 9.39±0.25(Predicted) |
Structure | |
Pointgroup C1 | |
Distorted tetrahedral | |
Hazards | |
NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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VG (IUPAC name: O,O-diethyl S-[2-(diethylamino)ethyl] phosphorothioate) (also called Amiton 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 VG 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.[1] VG has a toxicity of about 1/10 of VX similar to sarin. [2]
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in humans, its persistence in the environment, and its ability to enter the bloodstream through skin contact, it was withdrawn from the market. [3]
During the early 1950s, multiple chemical companies researching organophosphorus insecticides independently discovered their high toxicity.[4] 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[4], 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. [5][6][7]
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 VG 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, VG was no longer pursued for chemical warfare or as a pesticide.[6][7][8]
Although VX has been used as a chemical weapon, VG has not. The Chemical Weapons Convention (CWC) classifies VX as a Schedule 1 chemical and VG as a Schedule 2 chemical.[9] 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 VG 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.[10]
It is thought that North Korea may have military stockpiles of this chemical .[11]
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.[12]
Structure and Reactivity
[edit]Amiton is an organophosphate, specifically an organothiophosphate, characterized by two ethyl groups bonded to oxygen atoms and a triethylamine side group. This structure enables Amiton to undergo various chemical reactions.
Hydrolysis
[edit]Like most organophosphorus compounds, Amiton undergoes hydrolysis upon exposure to water[13]. This reaction primarily releases the sulfur-containing side group, though small quantities of the oxygen-linked ethyl groups may also be released[14][15]. Both reactions occur relatively slowly. While hydrolysis products typically show reduced toxicity, they still present potential health hazards[13].

Thiono-thiol Isomerization
[edit]Amiton may undergo thiono-thiol isomerization[13]. During this reaction, the phosphorus-oxygen (P=O) double bond converts into a single bond, while the single-bonded sulfur forms a double bond with phosphorus[16]. This rearrangement can produce potentially toxic compounds[13].
Decomposition
[edit]Upon heating, Amiton undergoes thermal decomposition. Similar to other organothiophosphates, this process generates sulfur oxides (SOₓ), nitrogen oxides (NOₓ), and phosphorus oxides (POₓ). These decomposition products are highly toxic, posing inhalation hazards[17].
Synthesis
[edit]Synthesis of Amiton
[edit]Amiton can be synthesized through the reaction of dialkylchlorothiophosphate and an amino thioalcohol, specifically O,O-diethyl phosphorochloridothioate and 2-diethylaminoethanethiol. The type of dialkylchlorothiophosphate (thiono or thiol) used significantly influences the reaction conditions. For thiono derivatives, precise temperature control is critical, whereas thiol derivatives are less sensitive to reaction temperature variations[18].
Synthesis of Dialkylchlorothiophosphates
[edit]Dialkylchlorothiophosphates are typically synthesized by reacting phosphorus trichloride (PCl₃) with alcohols or sulfides. The Regel method is commonly employed due to its high yields[18].

Synthesis of Amino Thioalcohols
[edit]Amino thioalcohols, such as 2-diethylaminoethanethiol, are synthesized by initially alkylating amines with alkyl halides like bromoethane to form secondary amines. These secondary amines subsequently react with ethylene sulfide to yield the desired amino thioalcohol[18].
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.[19].
Use and Efficacy
[edit]Originally developed as a potent insecticide, Amiton showed strong efficacy in controlling insect pests. However, its significant risks to humans and other non-target organisms led to its rapid withdrawal from agricultural use, despite its effectiveness against pests[20].
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. [21]. 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[22].
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[23]. 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[24]. 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[25], and parasympatholytic like atropine are used to reduce the effects of the accumulated acetylcholine[26]. 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[27][28]. The administration of these drugs should be done quickly after poisoning, otherwise the function of the enzyme cannot be restored[29].
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.[30][31]
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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