VX is an extremely toxic synthetic

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

in the

organophosphorus Organophosphorus compounds are organic compounds containing phosphorus. They are used primarily in pest control as an alternative to chlorinated hydrocarbons that persist in the environment. Some organophosphorus compounds are highly effective in ...

class, specifically, a thiophosphonate. In the class of

nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that ...

s, it was developed for military use in

chemical warfare Chemical warfare (CW) involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from nuclear warfare, biological warfare and radiological warfare, which together make up CBRN, the military acronym ...

after

translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...

of earlier discoveries of

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered a ...

toxicity in

pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...

research. In recent years, VX was found to be the agent used in the

assassination of Kim Jong-nam On 13 February 2017, the eldest son of Kim Jong-il and half-brother of Kim Jong-un, Kim Jong-nam, was attacked with the nerve agent VX at Kuala Lumpur International Airport in Malaysia. He had been exiled from North Korea in 2003 and had been ...

. In its pure form, VX is an oily, relatively non-volatile liquid that is amber-like in colour. Because of its low volatility, VX persists in environments where it is dispersed. VX, short for "venomous agent X", is one of the best known of the V nerve agents and was first discovered at

Porton Down Porton Down is a science park in Wiltshire, England, just northeast of the village of Porton, near Salisbury. It is home to two British government facilities: a site of the Ministry of Defence's Defence Science and Technology Laboratory (Dstl ...

by Ranajit Ghosh in England during the early 1950s based on research first done by

Gerhard Schrader Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...

, a chemist working for

IG Farben Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...

in Germany during the 1930s. It is now one of a broader V-series of agents which are classified as

s and have been used as a

chemical weapon A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as a ...

in various recorded deadly attacks. VX fatalities occur with exposure to tens of milligram quantities via inhalation or absorption through skin; VX is thus more potent than

sarin Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

. On such exposure, these agents severely disrupt the body's signaling between the nervous and

muscular system The muscular system is an organ (anatomy), organ system consisting of skeletal muscle, skeletal, smooth muscle, smooth, and cardiac muscle, cardiac muscle. It permits movement of the body, maintains posture, and circulates blood throughout the bo ...

s, leading to a prolonged

neuromuscular blockade Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors. In clin ...

flaccid paralysis Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associ ...

of all the muscles in the body including the diaphragm, and death by

asphyxiation Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that can i ...

. The danger of VX, in particular, lies in direct exposure to the chemical agent persisting where it was dispersed, and not through its evaporating and being distributed as a vapor; it is not considered a vapor hazard due to its relative non-volatility. VX is considered an

area denial weapon An area denial weapon is a defensive device used to prevent an adversary from occupying or traversing an area of land, sea or air. The specific method used does not have to be totally effective in preventing passage (and sometimes is not) as lon ...

due to these physical and biochemical characteristics. As a

, it is categorized as a

weapon of mass destruction A weapon of mass destruction (WMD) is a chemical, biological, radiological, nuclear, or any other weapon that can kill and bring significant harm to numerous individuals or cause great damage to artificial structures (e.g., buildings), natura ...

by the

United Nations The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and international security, security, develop friendly relations among nations, achieve international cooperation, and be ...

and is banned by the

Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...

of 1993, where production and stockpiling of VX exceeding per year is outlawed. The only exception is for "research, medical or pharmaceutical purposes outside a single small-scale facility in aggregate quantities not exceeding per year per facility".

Physical properties

VX is an odorless and tasteless chiral organophosphorous chemical with a molecular weight of 267.37 g/mol. Under standard conditions it is an amber-coloured liquid with a boiling point of , and a freezing point of . Its density is similar to that of water. It has a

log P Log most often refers to: * Trunk (botany), the stem and main wooden axis of a tree, called logs when cut ** Logging, cutting down trees for logs ** Firewood, logs used for fuel ** Lumber or timber, converted from wood logs * Logarithm, in mathem ...

value of 2.047, meaning it is relatively hydrophobic with about 100-fold more partitioning into octanol, over water. Its low

vapor pressure Vapor pressure (or vapour pressure in English-speaking countries other than the US; see spelling differences) or equilibrium vapor pressure is defined as the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phases ...

of gives it a low volatility, resulting in a high persistence in the environment. When weaponized, it can be dispersed as a liquid, aerosol or as a mixture with a

clay Clay is a type of fine-grained natural soil material containing clay minerals (hydrous aluminium phyllosilicates, e.g. kaolin, Al2 Si2 O5( OH)4). Clays develop plasticity when wet, due to a molecular film of water surrounding the clay par ...

talc Talc, or talcum, is a Clay minerals, clay mineral, composed of hydrated magnesium silicate with the chemical formula Mg3Si4O10(OH)2. Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thi ...

thickening agent.

Mechanism of action

VX is an

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...

. It blocks the function of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...

(AChE). Normally, when a

motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...

is stimulated, it releases the neurotransmitter

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

(ACh) into the space between the neuron and an adjacent muscle cell, the synaptic cleft. When acetylcholine binds to nicotinic receptors at the neuromuscular junction, it stimulates muscle contraction. To avoid a state of constant muscle contraction, the acetylcholine is then broken down (

hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

) into the inactive substances

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

and

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...

by AChE. VX blocks the action of AChE, resulting in an accumulation of acetylcholine in the space between the neuron and muscle cell. On a molecular level, this leads to the ongoing stimulation and eventual fatigue of all affected

muscarinic Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

and

nicotinic Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

ACh receptors. This results in initial violent contractions, followed by sustained supercontraction restricted to the fluid (

sarcoplasm Sarcoplasm is the cytoplasm of a muscle cell. It is comparable to the cytoplasm of other cells, but it contains unusually large amounts of glycogen (a polymer of glucose), myoglobin, a red-colored protein necessary for binding oxygen molecules tha ...

) of the subjunctional

endplate The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic i ...

and prolonged, depolarizing

.The prolonged blockade results in flaccid paralysis of all the muscles in the body, and it is such sustained paralysis of the

diaphragm muscle The thoracic diaphragm, or simply the diaphragm ( grc, διάφραγμα, diáphragma, partition), is a sheet of internal skeletal muscle in humans and other mammals that extends across the bottom of the thoracic cavity. The diaphragm is the ...

that causes death by

. Accumulation of acetylcholine in the brain also causes neuronal

excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...

, due to activation of

receptors and

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

release. The extreme toxicity of VX is partly due to the fact that the inhibitor was designed to be an excellent structural mimic for the transition state of the natural substrate (acetylcholine) of acetylcholinesterase. VX has a very high "on-rate" to react with the target enzyme and form a stable P-O-C bond (phosphorylation). However, compared with other highly toxic nerve agents like

soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiti ...

sarin Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound. The reaction products of acetylcholinesterase with VX before and after the "aging" reaction were solved near atomic resolution by

X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

to aid in antidote development. The X-ray structures revealed the specific parts of the VX molecule that interact with key residues and sub-sites of the target enzyme. The structural kinetic of phosphonylation followed by aging also showed an unexpected conformational change in the catalytic triad suggestive of an "induced fit" between the VX molecule and acetylcholinesterase.

Chemistry

Synthesis

VX is

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

at its

phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...

atom. The individual

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

s are identified as ''S''_P-(−)-VX, and ''R''_P-(+)-VX (where the "P" subscript highlights that the chirality is at phosphorus). VX is produced via the transester process, which gives a

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

mixture of the two enantiomers. This entails a series of steps whereby

phosphorus trichloride Phosphorus trichloride is an inorganic compound with the chemical formula PCl3. A colorless liquid when pure, it is an important industrial chemical, being used for the manufacture of phosphites and other organophosphorus compounds. It is toxic a ...

methylated In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

to produce methyl phosphonous dichloride. The resulting material is reacted with

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

to form a

diester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...

. This is then

transesterified In organic chemistry, transesterification is the process of exchanging the organic group R″ of an ester with the organic group R' of an alcohol. These reactions are often catalyzed by the addition of an acid or base catalyst. The reaction ca ...

with ''N'',''N''-diisopropylaminoethanol to produce the mixed

phosphonite In organic chemistry, phosphonites are organophosphorus compounds with the formula P(OR)2R. They are found in some pesticides and are used as ligands. Preparation Although they are derivatives of phosphonous acid (RP(OH)2), they are not prepar ...

. Finally, this immediate precursor is reacted with sulfur to form VX. VX can also be delivered in binary chemical weapons which mix in-flight to form the agent prior to release. Binary VX is referred to as VX2, and is created by mixing ''O''-(2-diisopropylaminoethyl) ''O′''-ethyl methylphosphonite ( Agent QL) with elemental sulfur (Agent NE) as is done in the Bigeye aerial chemical bomb. It may also be produced by mixing with sulfur compounds, as with the liquid dimethyl polysulfide mixture (Agent NM) in the canceled XM736 8-inch projectile program.

Solvolysis

Like other

nerve agents, VX may be destroyed by reaction with strong nucleophiles. The reaction of VX with concentrated aqueous

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

results in two competing

solvolysis In chemistry, solvolysis is a type of nucleophilic substitution (S1/S2) or elimination reaction, elimination where the nucleophile is a solvent molecule. Characteristic of S1 reactions, solvolysis of a chirality (chemistry), chiral reactant affor ...

reactions: cleavage of either the P–O or P–S esters. Although the P–S cleavage is the dominant pathway, the product of P–O bond cleavage is the toxic phosphonic thioester

EA-2192 EA-2192 is an extremely toxic degradation product of the VX (nerve agent), VX nerve agent. It is a white solid that is very soluble and stable in water. EA-2192 is an extremely potent acetylcholinesterase inhibitor. It is almost as toxic as VX it ...

and both reactions are slow. In contrast, reaction with the

hydroperoxide Hydroperoxides or peroxols are compounds containing the hydroperoxide functional group (ROOH). If the R is organic, the compounds are called organic hydroperoxides. Such compounds are a subset of organic peroxides, which have the formula ROOR. ...

anion (hydroperoxidolysis) leads to exclusive cleavage of the P–S bond and a more rapid overall reaction. VX-solvolysis-P-S-2D-skeletal

Medical aspects

Symptoms of exposure

Early symptoms of percutaneous exposure (skin contact) include local sweating and muscular twitching at the area of exposure, followed by nausea or vomiting. Early symptoms of exposure to VX vapor include

rhinorrhea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies ( hay fever) or certain viral infections, such as the common cold or COVID- ...

(runny nose) and/or tightness in the chest with shortness of breath (bronchial constriction).

Miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

(pinpointing of the pupils) may be an early sign of agent exposure, but is not usually used as the only indicator of exposure.

Toxicology

VX is a "particularly toxic nerve agent". The potentially fatal dose is only slightly higher than the dose having any effect at all, and the effects of a fatal dose are so rapid that there is little time for treatment. The

median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...

(LD₅₀), the exposure required to kill half of a tested population, as estimated for 70 kg human males via exposure to the skin is reported to be 5–, and the lethal concentration time (LCt₅₀), measuring the concentration of the vapor or aerosol per length of time exposed, is estimated for VX to be 10–15 mg·min/m³ for exposure time of two minutes at a minute volume of 15 L (minute volume of 15 L corresponds to slight physical activity like slow walking).

Treatment

When treating VX exposure, primary consideration is given to removal of the liquid agent from the skin, before removal of the individual to an uncontaminated area or atmosphere. After this, the victim is decontaminated by washing the contaminated areas with household bleach and flushing with clean water, followed by removal of contaminated clothing and further skin decontamination. When possible, decontamination is completed before the casualty is taken for further medical treatment. An individual known to have been exposed to a nerve-agent, or who exhibits definite signs or symptoms of nerve-agent exposure is generally given the antidotes

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...

and

pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosphat ...

(2-PAM), and in the case of convulsions an injected sedative/antiepileptic such as

diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...

. In several nations the nerve agent antidotes are issued for military personnel in the form of an

autoinjector An autoinjector (or auto-injector) is a medical device designed to deliver a dose of a particular drug. The injectors were initially designed to overcome the hesitation associated with self-administration of the needle-based drug delivery device ...

such as the United States military

Mark I NAAK In the United States military, the Mark I NAAK, or MARK I Kit, ("Nerve Agent Antidote Kit") is a dual-chamber autoinjector: Two anti-nerve agent drugs— atropine sulfate and pralidoxime chloride—each in injectable form, constitute the kit. ...

. Atropine blocks a subset of acetylcholine receptors known as

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

s (mAchRs), so that the buildup of acetylcholine produced by loss of the acetylcholinesterase function has a reduced effect on their target receptor. 2-PAM reactivates the acetylcholinesterase enzyme (AChE), thus reversing the effects of VX. VX and other organophosphates block AChE activity by binding to and covalently inactivating the enzyme via transfer of the

phosphonate In organic chemistry, phosphonates or phosphonic acids are organophosphorus compounds containing groups (where R = alkyl, aryl, or just hydrogen). Phosphonic acids, typically handled as salts, are generally nonvolatile solids that are poorly ...

moiety from VX to the

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

of AChE; this inactivates AChE and produces an inactive by-product from the remaining portion of the VX molecule. Pralidoxime (2-PAM) removes this phosphate group.

Diagnostic tests

Controlled studies in humans have shown that minimally toxic doses cause 70–75% depression of

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

cholinesterase The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters: : an acylcholine + H2O = choline + a carboxylate Several of these serve as neurotransmitters ...

within several hours of exposure. The serum level of ethyl methylphosphonic acid (EMPA), a VX hydrolysis product, was measured to confirm exposure in one poisoning victim. There also exist procedures for determination of VX hydrolysis products in urine and of VX adducts to albumin in blood.

History

Discovery

The chemists Ranajit Ghosh and J. F. Newman discovered the V-series nerve agents at the British firm ICI in 1952, patenting diethyl ''S''-2-diethylaminoethyl phosphonothioate ( agent VG) in November 1952. Further commercial research on similar compounds ceased in 1955 when its lethality to humans was discovered. The U.S. started production of large amounts of VX in 1961 at

Newport Chemical Depot The Newport Chemical Depot, previously known as the Wabash River Ordnance Works and the Newport Army Ammunition Plant, was a bulk chemical storage and destruction facility that was operated by the United States Army. It is located near Newpor ...

. The discovery occurred when the chemists were investigating a class of

compounds (organophosphate

esters In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...

of substituted aminoethanethiols). Like

, an earlier investigator of organophosphates, Ghosh found that they were quite effective

s. In 1954, ICI put one of them on the market under the trade name Amiton. It was subsequently withdrawn, as it was too toxic for safe use. The toxicity did not go unnoticed, and samples of it were sent to the British Armed Forces research facility at

for evaluation. After the evaluation was complete, several members of this class of compounds became a new group of nerve agents, the V agents. The best-known of these is probably VX, assigned the UK

Rainbow Code The Rainbow Codes were a series of code names used to disguise the nature of various British military research projects. They were mainly used by the Ministry of Supply from the end of the Second World War until 1958, when the ministry was broke ...

Purple Possum, with the Russian V-Agent (VR) coming a close second (Amiton is largely forgotten as VG). The name is a contraction of the words "venomous agent X". Beginning in 1959, the United States Army began volunteer testing of VX in humans. Dr. Van M. Sim underwent an intravenous infusion of VX to evaluate its effects and to establish a baseline for future experimentation. After approximately 3.5 hours following initial administration of the agent, Sim suddenly became pale and delirious. The experiment was immediately terminated to preserve his life. In their conclusion, the researchers estimated that 2.12 μg/kg of VX delivered intravenously over the course of several hours would be the maximum tolerable dosage and that any more would risk death in a human subject.

Use as a weapon

In 1988, a United Nations inquiry established that

Cuba Cuba ( , ), officially the Republic of Cuba ( es, República de Cuba, links=no ), is an island country comprising the island of Cuba, as well as Isla de la Juventud and several minor archipelagos. Cuba is located where the northern Caribbea ...

was responsible for deploying VX against Angolan insurgents during the

Angolan Civil War The Angolan Civil War ( pt, Guerra Civil Angolana) was a civil war in Angola, beginning in 1975 and continuing, with interludes, until 2002. The war immediately began after Angola became independent from Portugal in November 1975. The war was ...

. UN toxicologists obtained trace elements of VX from soil, water, and plant samples taken from areas where Cuban troops had recently carried out counter-insurgency operations. Patients demonstrating symptoms of exposure to nerve agents first began appearing in Angolan hospitals around 1984. There was evidence of a combination of chemical agents having been used by

Iraq Iraq,; ku, عێراق, translit=Êraq officially the Republic of Iraq, '; ku, کۆماری عێراق, translit=Komarî Êraq is a country in Western Asia. It is bordered by Turkey to Iraq–Turkey border, the north, Iran to Iran–Iraq ...

against the Kurds in the

Halabja chemical attack The Halabja massacre ( ku, Kêmyabarana Helebce کیمیابارانی ھەڵەبجە), also known as the Halabja chemical attack, was a massacre of Kurdish people that took place on 16 March 1988, during the closing days of the Iran–Iraq War ...

in 1988 under

Saddam Hussein Saddam Hussein ( ; ar, صدام حسين, Ṣaddām Ḥusayn; 28 April 1937 – 30 December 2006) was an Iraqi politician who served as the fifth president of Iraq from 16 July 1979 until 9 April 2003. A leading member of the revolution ...

, including VX. Hussein later testified to

UNSCOM United Nations Special Commission (UNSCOM) was an inspection regime created by the United Nations to ensure Iraq's compliance with policies concerning Iraqi production and use of weapons of mass destruction after the Gulf War. Between 1991 and 19 ...

that Iraq had researched VX, but had failed to weaponize the agent due to production failure. After U.S. and allied forces invaded Iraq, no VX agent or production facilities were found. However, UNSCOM laboratories detected traces of VX on warhead remnants. In December 1994 and January 1995, Masami Tsuchiya of

Aum Shinrikyo , formerly , is a Japanese doomsday cult founded by Shoko Asahara in 1987. It carried out the deadly Tokyo subway sarin attack in 1995 and was found to have been responsible for the Matsumoto sarin attack the previous year. The group says ...

synthesized of VX which was used to attack three people. Two people were injured and one 28-year-old man died, who was the first victim of VX ever documented in the world at that time. The VX victim, whom

Shoko Asahara , born , was the founder and leader of the Japanese doomsday cult known as Aum Shinrikyo. He was convicted of masterminding the deadly 1995 sarin gas attack on the Tokyo subway, and was also involved in several other crimes. Asahara was sentenced ...

had suspected as a spy, was attacked at 7:00 am on 12 December 1994 on the street in Osaka by Tomomitsu Niimi and another AUM member, who sprinkled the nerve agent on his neck. He chased them for about 90 metres (100 yd) before collapsing, dying ten days later without ever coming out of a deep coma. Doctors in the hospital suspected at the time he had been poisoned with an organophosphate pesticide, but the cause of death was pinned down only after cult members arrested for the

Tokyo subway sarin attack The was an act of domestic terrorism perpetrated on 20 March 1995, in Tokyo, Japan, by members of the cult movement Aum Shinrikyo. In five coordinated attacks, the perpetrators released sarin on three lines of the Tokyo Metro (then ''Teito Rapi ...

confessed to the killing. Metabolites of VX such as ethyl methylphosphonate, methylphosphonic acid and diisopropyl-2-(methylthio)ethylamine were later found in samples of the victim's blood seven months after his murder. Unlike the cases for

Kim Jong-nam Kim Jong-nam (, ; 10 May 1971 – 13 February 2017) was the eldest son of North Korean leader Kim Jong-il. From roughly 1994 to 2001, he was considered the heir apparent to his father. He was thought to have fallen out of favour after em ...

, half-brother of North Korean leader

Kim Jong-un Kim Jong-un (; , ; born 8 January 1982) is a North Korean politician who has been Supreme Leader of North Korea since 2011 and the leader of the Workers' Party of Korea (WPK) since 2012. He is a son of Kim Jong-il, who was North Korea's sec ...

, died after an assault at

Kuala Lumpur International Airport Kuala Lumpur International Airport (KLIA) is Malaysia's main international airport. It is located in the Sepang District of Selangor, approximately south of Kuala Lumpur and serves the city's greater conurbation. KLIA is the largest and b ...

Malaysia Malaysia ( ; ) is a country in Southeast Asia. The federation, federal constitutional monarchy consists of States and federal territories of Malaysia, thirteen states and three federal territories, separated by the South China Sea into two r ...

. According to the authorities he was murdered by poisoning with VX which was found on his face. The authorities further reported that one of the women suspected of applying the nerve agent experienced some physical symptoms of VX-poisoning. The director of a non- proliferation research program of the

Middlebury Institute of International Studies at Monterey The Middlebury Institute of International Studies at Monterey (MIIS), formerly known as the Monterey Institute of International Studies, is an American graduate school of Middlebury College, a private college in Middlebury, Vermont. Established ...

stated that VX fumes would have killed the suspected attackers even if they had been wearing gloves, suggesting that the VX was applied as two non-lethal components that would mix to form VX only on the victim's face.

Worldwide stockpiles

Some countries known to possess VX are the United States, the United Kingdom, Russia, North Korea, and Syria. A

Sudan Sudan ( or ; ar, السودان, as-Sūdān, officially the Republic of the Sudan ( ar, جمهورية السودان, link=no, Jumhūriyyat as-Sūdān), is a country in Northeast Africa. It shares borders with the Central African Republic t ...

ese pharmaceutical facility, the

Al-Shifa pharmaceutical factory The Al-Shifa (الشفاء, Arabic for "healing") pharmaceutical factory in Khartoum North, Sudan, was constructed between 1992 and 1996 with components imported from Germany, India, Italy, Sweden, Switzerland, Thailand and the United ...

, was bombed by the U.S. in 1998 acting on information that it produced VX and that the origin of the agent was associated with both Iraq and

Al Qaeda Al-Qaeda (; , ) is an Islamic extremist organization composed of Salafist jihadists. Its members are mostly composed of Arabs, but also include other peoples. Al-Qaeda has mounted attacks on civilian and military targets in various countr ...

. The U.S. had obtained soil samples identified as containing ''O''-ethyl hydrogen methylphosphonothioate (EMPTA), a chemical used in the production of VX which may also have commercial applications. Chemical weapons experts later suggested that the widely used

fonofos __TOC__ Fonofos is an organothiophosphate insecticide primarily used on corn. ...

organophosphate insecticide could have been mistaken for EMPTA. Cuba obtained VX during the 1980s and deployed it during its military intervention in Angola. In 1969, the U.S. government cancelled its chemical weapons programs, banned the production of VX in the United States, and began the destruction of its stockpiles of agents by a variety of methods. Early disposal included the U.S. Army's

CHASE Chase or CHASE may refer to: Businesses * Chase Bank, a national bank based in New York City, New York * Chase Aircraft (1943–1954), a defunct American aircraft manufacturing company * Chase Coaches, a defunct bus operator in England * Chase Co ...

(Cut Holes And Sink 'Em) program, in which old ships were filled with chemical weapons stockpiles and then

scuttled Scuttling is the deliberate sinking of a ship. Scuttling may be performed to dispose of an abandoned, old, or captured vessel; to prevent the vessel from becoming a navigation hazard; as an act of self-destruction to prevent the ship from being ...

. CHASE 8 was conducted on 15 June 1967, in which the steamship ''Cpl. Eric G. Gibson'' was filled with 7,380 VX rockets and scuttled in of water off the coast of

Atlantic City, New Jersey Atlantic City, often known by its initials A.C., is a coastal resort city in Atlantic County, New Jersey, United States. The city is known for its casinos, boardwalk, and beaches. In 2020, the city had a population of 38,497.

Incineration Incineration is a waste treatment process that involves the combustion of substances contained in waste materials. Industrial plants for waste incineration are commonly referred to as waste-to-energy facilities. Incineration and other high ...

was used for VX stockpile destruction starting in 1990 with

Johnston Atoll Chemical Agent Disposal System Johnston Atoll Chemical Agent Disposal System (JACADS) was the U.S. Army's first chemical munitions disposal facility. It was located on Johnston Island, at Johnston Atoll and completed its mission and ceased operation in 2000. Background Prior ...

in the North Pacific with other incineration plants following at

Deseret Chemical Depot The Deseret Chemical Depot () was a U.S. Army chemical weapon storage area located in Utah, 60 miles (100 km) southwest of Salt Lake City. It is related to the Tooele Chemical Agent Disposal Facility. History The area was used to store c ...

Pine Bluff Arsenal The Pine Bluff Arsenal is a United States Army installation in Jefferson County, Arkansas, about eight miles northwest of Pine Bluff and thirty miles southeast of Little Rock. Pine Bluff Arsenal is one of nine Army installations in the United ...

Umatilla Chemical Depot The Umatilla Chemical Depot, (UMCD) based in Umatilla, Oregon, was a U.S. Army installation in the United States that stored chemical weapons. The chemical weapons originally stored at the depot consisted of various live munitions and storage co ...

and Anniston Army Depot with the last of the VX inventory destroyed on 24 December 2008.

Stockpile elimination

Worldwide, VX disposal has continued since 1997 under the mandate of the

. When the convention entered force, the parties declared worldwide stockpiles of of VX. As of December 2015, 98% of the stockpiles had been destroyed. In fiscal year 2008, the

U.S. Department of Defense The United States Department of Defense (DoD, USDOD or DOD) is an executive branch department of the federal government charged with coordinating and supervising all agencies and functions of the government directly related to national secur ...

released a study finding that the United States had dumped at least of VX into the Atlantic Ocean off the coasts of New York/New Jersey and Florida between 1969 and 1970. This material consisted of nearly 22,000 M55 rockets, 19 bulk containers holding each, and one M23 chemical landmine. The

began VX stockpile elimination using chemical neutralization in 2005. VX was hydrolyzed to much less toxic byproducts by using concentrated caustic solution, and the resulting waste was then shipped off-site for further processing. Technical and political issues regarding this secondary byproduct resulted in delays, but the depot completed their VX stockpile destruction in August 2008. The remaining VX stockpile in the U.S. was treated by the

Blue Grass Chemical Agent-Destruction Pilot Plant The Blue Grass Chemical Agent-Destruction Pilot Plant (BGCAPP) is a facility built to destroy the chemical weapons stockpile at the Blue Grass Army Depot (BGAD), near Richmond, Kentucky. Since 1944, the Army stored 523 short tons (474 t) of nerv ...

in Kentucky, part of the

Program Executive Office, Assembled Chemical Weapons Alternatives The Program Executive Office, Assembled Chemical Weapons Alternatives (PEO ACWA) is responsible for the safe and environmentally sound destruction of chemical weapons stockpiles stored at the Blue Grass Army Depot, Kentucky and the U.S. Army Puebl ...

program. The program was established as an alternative to the incineration process successfully used by the Army Chemical Materials Agency, which completed its stockpile destruction activities in March 2012. The Blue Grass Pilot Plant has been plagued by repeated cost over-runs and schedule slippages since its inception. In Russia, the U.S. provided support for these destruction activities with the Nunn-Lugar Global Cooperation Initiative. The Initiative has been able to convert a former chemical weapons depot at Shchuchye,

Kurgan Oblast Kurgan Oblast (russian: Курга́нская о́бласть, ''Kurganskaya oblast'') is a federal subject of Russia (an oblast). Its administrative center is the city of Kurgan. In June 2014, the population was estimated to be 874,100,Kurgan ...

into a facility to destroy those chemical weapons. The new facility, which opened in May 2009, has been working on eliminating the nearly of nerve agents held at the former storage complex. However, this facility only held about 14% of Russian chemical weapons, which were stored at seven sites.

In popular culture

One of the best-known references to VX in popular culture is its use in the 1996 film '' The Rock'', which centers on a threatened VX attack on

San Francisco San Francisco (; Spanish language, Spanish for "Francis of Assisi, Saint Francis"), officially the City and County of San Francisco, is the commercial, financial, and cultural center of Northern California. The city proper is the List of Ca ...

from the island of

Alcatraz Alcatraz Island () is a small island in San Francisco Bay, offshore from San Francisco, California, United States. The island was developed in the mid-19th century with facilities for a lighthouse, a military fortification, and a military pris ...

. The film uses

artistic license Artistic license (alongside more contextually-specific derivative terms such as poetic license, historical license, dramatic license, and narrative license) refers to deviation from fact or form for artistic purposes. It can include the alterat ...

, notably with VX being ascribed corrosive powers it does not possess, permitting an early scene in which a VX victim is shown with his face melting, rather than dying through asphyxiation. It is also shown as being bright green, a colour often used in Hollywood to represent 'danger' when applied to substances, rather than amber. As well, its delivery and dispersal mechanism is based around a chain of fictional glass balls that hold the substance as a gel solution. Other references to VX are found in the 2012 film ''

It's a Disaster ''It's a Disaster'' is a 2012 American art-house black comedy film written and directed by Todd Berger. The film was made by Los Angeles-based comedy group The Vacationeers and stars Rachel Boston, David Cross, America Ferrera, Jeff Grace, Erinn ...

'' in which it is revealed that a nearby

dirty bomb A dirty bomb or radiological dispersal device is a radiological weapon that combines radioactive material with conventional explosives. The purpose of the weapon is to contaminate the area around the dispersal agent/conventional explosion with ...

attack was a VX attack, prompting the four couples to contemplate a suicide pact, as well as the 2015 film '' Mission: Impossible – Rogue Nation'', in which series protagonist

Ethan Hunt Ethan Matthew Hunt is a fictional character and the protagonist of the ''Mission: Impossible'' film series. He is portrayed by Tom Cruise. Appearances ''Mission: Impossible'' (1996) In the first film, Hunt acts as the IMF point man for an ...

steals VX nerve gas from

Chechen separatists The Chechen Republic of Ichkeria (; ce, Нохчийн Республик Ичкери, Nóxçiyn Respublik Içkeri; russian: Чеченская Республика Ичкерия; abbreviated as "ChRI" or "CRI") was a ''de facto'' state that ...

on their way to Syria. Also season 5 of the TV series '' 24'', has a similar storyline.24 - Day 5: 12:00 p.m.-1:00 p.m.
30 January 2006. The fifth episode of the 2020 anime series '' The Millionaire Detective Balance: Unlimited'' features a tear gas bomb with canisters loaded with VX gas and placed inside a cabinet of a

safe room A safe room or panic room is a fortified room that is installed in a private residence or business to provide a safe shelter, or hiding place, for the inhabitants in the event of a break in, home invasion, tornado, terror attack, or other thr ...

within the embassy; the protagonist Daisuke Kambe and two other characters were trapped inside the room after relocating themselves due to security reasons, and figuring out how to escape before the bomb detonates. The album ''

VIVIsectVI ''VIVIsectVI'' (pronounced "vivisect six") is the fourth studio album by Canadian electro-industrial band Skinny Puppy. It was released on September 12, 1988 through Nettwerk. Despite tackling controversial topics like animal rights, chemical w ...

'' by the

industrial Industrial may refer to: Industry * Industrial archaeology, the study of the history of the industry * Industrial engineering, engineering dealing with the optimization of complex industrial processes or systems * Industrial city, a city dominate ...

band

Skinny Puppy Skinny Puppy is a Canadian industrial music group formed in Vancouver in 1982. The group is among the founders of the industrial rock and electro-industrial genres. Initially envisioned as an experimental side-project by cEvin Key (Kevin Crompton ...

contains a song about

chemical weapons A chemical weapon (CW) is a specialized Ammunition, munition that uses chemicals chemical engineering, formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be an ...

called "VX Gas Attack". In the

BBC #REDIRECT BBC #REDIRECT BBC Here i going to introduce about the best teacher of my life b BALAJI sir. He is the precious gift that I got befor 2yrs . How has helped and thought all the concept and made my success in the 10th board exam. ...

...

show '' Spooks'', series 2 episode 5, a dirty bomb using VX is said to have gone off in a 'training exercise'. In the video game ''

Everybody's Gone to the Rapture ''Everybody's Gone to the Rapture'' is an adventure video game developed by The Chinese Room and published by Sony Computer Entertainment for the PlayStation 4. It is a story-based game, taking place in a small English village whose inhabitants ...

'', VX is alluded to as a nerve agent used by the government to contain a pattern which infects and kills humans and other animals. In the book ''Nightshade'', the twelfth book in the

Alex Rider ''Alex Rider'' is a series of spy novels written by British author Anthony Horowitz. The novels revolve around a teenage spy named Alex Rider and is primarily aimed towards young adults. The series currently comprises thirteen novels, as we ...

Series, VX plays a major role, as it is used by terrorists in an attempt kill over half of the British government. The second episode of the TV series '' Seal Team'' (season 1) focuses on a chemical weapons lab in an abandoned hospital, producing VX gas. In the

Netflix Netflix, Inc. is an American subscription video on-demand over-the-top streaming service and production company based in Los Gatos, California. Founded in 1997 by Reed Hastings and Marc Randolph in Scotts Valley, California, it offers a fil ...

show ''

Designated Survivor In the United States, a designated survivor (or designated successor) is a named individual in the presidential line of succession, chosen to stay at an undisclosed secure location, away from events such as State of the Union addresses and pre ...

'', agent Hannah Wells is killed by VX in season 3, episode 7. In the

CBS CBS Broadcasting Inc., commonly shortened to CBS, the abbreviation of its former legal name Columbia Broadcasting System, is an American commercial broadcast television and radio network serving as the flagship property of the CBS Entertainm ...

show ''

MacGyver Angus "Mac" MacGyver is the title character and the protagonist in the TV series ''MacGyver''. He is played by Richard Dean Anderson in the 1985 original series. Lucas Till portrays a younger version of MacGyver in the 2016 reboot. In both po ...

'', season 2 episode 9, a VX canister is the main plot point. In the

Crackle Crackle or crackling may refer to: Foods * Cracklings, the tissue remaining after lard and tallow have been extracted from animal fats ** Pork rinds in American English, pork scratchings in British English when served in small pieces as a snac ...

show '' Startup'', American soldiers discover a computer used by apparent terrorists in

Aleppo, Syria )), is an adjective which means "white-colored mixed with black". , motto = , image_map = , mapsize = , map_caption = , image_map1 = ...

. "VX components" are displayed as an item for purchase on the computer, which is logged into Araknet, a

dark web The dark web is the World Wide Web content that exists on ''darknets'': overlay networks that use the Internet but require specific software, configurations, or authorization to access. Through the dark web, private computer networks can communi ...

created by the protagonists of the series.

References

External links

*
Oxford website on Nerve Agents

CDC Facts About VX

U.S. Army's Chemical Materials Agency (CMA)

CBW Info

– Article from ''The New York Times'' {{DEFAULTSORT:Vx (Nerve Agent) Acetylcholinesterase inhibitors V-series nerve agents Phosphonothioates Chemical weapons of the United States United Kingdom chemical weapons program British inventions Ethyl esters Diisopropylamino compounds