VX (nerve Agent)
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VX is an extremely toxic
synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
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 class, specifically, a thiophosphonate. In the class of
nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...
s, it was developed for military use in chemical warfare after
translation Translation is the communication of the semantics, 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 English la ...
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 ...
toxicity in
pesticide Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for approximately 50% of all p ...
research. In its pure form, VX is an oily, relatively
non-volatile Non-volatile memory (NVM) or non-volatile storage is a type of computer memory that can retain stored information even after power is removed. In contrast, volatile memory needs constant power in order to retain data. Non-volatile memory typ ...
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 originated from pesticide development work at
Imperial Chemical Industries Imperial Chemical Industries (ICI) was a British Chemical industry, chemical company. It was, for much of its history, the largest manufacturer in Britain. Its headquarters were at Millbank in London. ICI was listed on the London Stock Exchange ...
(ICI). It was developed further at Porton Down in England during the early 1950s, based on research first done by Gerhard Schrader, a chemist working for
IG Farben I. G. Farbenindustrie AG, commonly known as IG Farben, was a German Chemical industry, chemical and Pharmaceutical industry, pharmaceutical conglomerate (company), conglomerate. It was formed on December 2, 1925 from a merger of six chemical co ...
in Germany during the 1930s. It is now one of a broader V-series of agents which are classified as
nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...
s. VX has been allegedly used in warfare and has been used in several assassinations. The brother of North Korean leader
Kim Jong Un Kim Jong Un (born 8 January 1983 or 1984) is a North Korean politician and dictator who has served as supreme leader of North Korea since 2011 and general secretary of the Workers' Party of Korea (WPK) since 2012. He is the third son of Kim ...
, Kim Jong Nam, had the substance thrown in his face in
Kuala Lumpur International Airport Kuala Lumpur International Airport is the main international airport serving Kuala Lumpur, the capital of Malaysia. It is located in the Sepang District of Selangor, approximately south of downtown Kuala Lumpur and serves the Greater Kuala L ...
on February 13, 2017, by two women. He died while being rushed to hospital approximately 15 minutes later. The substance is extremely deadly: VX fatalities occur with exposure to tens of milligram quantities via inhalation or absorption through skin. It is more potent than sarin, another nerve agent with a similar
mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...
. 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,
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 all the tissues and organs, some more rapidly than others. There are ...
. 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 war offensive and defensive and device used to prevent an adversary from occupying or traversing an area of land, sea or air. The specific method may not be totally effective in preventing passage, but is sufficient to ...
due to these physical and biochemical characteristics. 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 ...
, it is categorized as a
weapon of mass destruction A weapon of mass destruction (WMD) is a biological, chemical, radiological, nuclear, or any other weapon that can kill or significantly harm many people or cause great damage to artificial structures (e.g., buildings), natural structures ( ...
by the
United Nations The United Nations (UN) is the Earth, global intergovernmental organization established by the signing of the Charter of the United Nations, UN Charter on 26 June 1945 with the stated purpose of maintaining international peace and internationa ...
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 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 equilibrium vapor pressure is the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phases (solid or liquid) at a given temperature in a closed system. The equilibrium vapor pressure is an indicat ...
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. kaolinite, ). Most pure clay minerals are white or light-coloured, but natural clays show a variety of colours from impuriti ...
or
talc Talc, or talcum, is a clay mineral composed of hydrated magnesium silicate, with the chemical formula . Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thickening agent and lubricant ...
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 an ...
. It blocks the function of the
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, 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 th ...
(AChE). Normally, when a
motor neuron A motor neuron (or motoneuron), also known as 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 o ...
is stimulated, it releases the neurotransmitter
acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...
(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) 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 compone ...
and
choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...
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 A muscarinic acetylcholine receptor agonist, also simply known as a muscarinic agonist or as a muscarinic agent, is an agent that activates the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, lab ...
and nicotinic ACh receptors. This results in initial violent contractions, followed by sustained supercontraction restricted to the fluid ( sarcoplasm) of the subjunctional endplate and prolonged, depolarizing neuromuscular blockade. The prolonged blockade results in flaccid paralysis of all the muscles in the body, and it is such sustained paralysis of the diaphragm muscle that causes 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 all the tissues and organs, some more rapidly than others. There are ...
. Accumulation of acetylcholine in the brain also causes neuronal
excitotoxicity In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...
, due to activation of nicotinic receptors and
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
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 or sarin, VX undergoes relatively slow "aging". Aging is a time-dependent side reaction (loss of an alkoxyl group) that occurs on nerve agents after phosphorylation and renders the nerve agent-acetylcholinesterase complex highly resistant to regeneration by any known antidote. Slower aging by VX suggests it should be possible to develop more effective antidotes and treatments. The reaction products of acetylcholinesterase with VX before and after the "aging" reaction were solved in near atomic resolution by
X-ray crystallography X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
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 phosphorylation 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 language, Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is dist ...
at its
phosphorus Phosphorus is a chemical element; it has Chemical symbol, symbol P and atomic number 15. All elemental forms of phosphorus are highly Reactivity (chemistry), reactive and are therefore never found in nature. They can nevertheless be prepared ar ...
atom. The individual
enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...
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 a mixture that has equal amounts (50:50) 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 r ...
mixture of the two enantiomers. This entails a series of steps whereby phosphorus trichloride is
methylated Methylation, in the chemical sciences, is 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 term ...
to produce methyl phosphonous dichloride. The resulting material is reacted with
ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
to form a diester. This is then transesterified with ''N'',''N''-diisopropylaminoethanol to produce QL, a mixed phosphonite. Finally, this immediate precursor is reacted with
sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...
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 QL with sulfur 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 (known as NM) in the canceled XM736 8-inch projectile program.


Solvolysis

Like other organophosphorus 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 . It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly corrosive base (chemistry), ...
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 and both reactions are slow. In contrast, reaction with the
hydroperoxide Hydroperoxides or peroxols are Chemical compound, compounds of the form ROOH, where R stands for any group, typically Organic compound, organic, which contain the hydroperoxy functional group (). Hydroperoxide also refers to the hydroperoxide anio ...
anion (hydroperoxidolysis) leads to exclusive cleavage of the P–S bond and a more rapid overall reaction.


Symptoms of exposure

Early symptoms of 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 (American English), also spelled rhinorrhoea or rhinorrhœa (British English), or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is an extremely common condition. It is a common symptom of allergie ...
(runny nose) and 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 extremely toxic. 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 given substance. The value of LD50 for a substance is the dose re ...
(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 to 10 mg.


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 give ...
and pralidoxime (2-PAM), and in the case of convulsions an injected sedative or antiepileptic such as
diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...
. In several nations the nerve agent antidotes are issued for military personnel in the form of an autoinjector such as the United States military Mark I NAAK. Atropine blocks a subset of acetylcholine receptors known as
muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...
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 Functional group, groups, where R is an organic group (alkyl, aryl). If R is hydrogen then the compound is a Phosphite_ester#Chemistry_of_HP(O)(OR ...
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, the ''binding s ...
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), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
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 neurotransmitte ...
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
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 ...
compounds (organophosphate
esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...
of substituted aminoethanethiols). Like Gerhard Schrader, an earlier investigator of organophosphates, Ghosh found that they were quite effective
pesticide Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for approximately 50% of all p ...
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 government research facility at Porton Down in
Wiltshire Wiltshire (; abbreviated to Wilts) is a ceremonial county in South West England. It borders Gloucestershire to the north, Oxfordshire to the north-east, Berkshire to the east, Hampshire to the south-east, Dorset to the south, and Somerset to ...
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 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, is an island country, comprising the island of Cuba (largest island), Isla de la Juventud, and List of islands of Cuba, 4,195 islands, islets and cays surrounding the main island. It is located where the ...
was responsible for deploying VX against Angolan insurgents during the
Angolan Civil War The Angolan Civil War () was a civil war in Angola, beginning in 1975 and continuing, with interludes, until 2002. The war began immediately after Angola became independent from Portugal in November 1975. It was a power struggle between two for ...
. 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, officially the Republic of Iraq, is a country in West Asia. It is bordered by Saudi Arabia to Iraq–Saudi Arabia border, the south, Turkey to Iraq–Turkey border, the north, Iran to Iran–Iraq border, the east, the Persian Gulf and ...
against the Kurds in the Halabja chemical attack in 1988 under
Saddam Hussein Saddam Hussein (28 April 1937 – 30 December 2006) was an Iraqi politician and revolutionary who served as the fifth president of Iraq from 1979 until Saddam Hussein statue destruction, his overthrow in 2003 during the 2003 invasion of Ira ...
, including VX. Hussein later testified to UNSCOM 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 , better known by their former name , is a Japanese new religions, Japanese new religious movement and 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 respo ...
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 had suspected as a spy, was attacked at 7:00 am on December 12, 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 a Chemical terrorism, chemical domestic terrorism, domestic terrorist attack perpetrated on 20 March 1995, in Tokyo, Japan, by members of the Aum Shinrikyo cult. In five coordinated attacks, the perpetrators released sarin on three line ...
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 sarin gas (the Matsumoto incident and the attack on the Tokyo subway), VX was not used for mass murder. On February 13, 2017, Kim Jong-nam, half-brother of North Korean leader
Kim Jong-un Kim Jong Un (born 8 January 1983 or 1984) is a North Korean politician and dictator who has served as supreme leader of North Korea since 2011 and general secretary of the Workers' Party of Korea (WPK) since 2012. He is the third son of Kim ...
, died after an assault at
Kuala Lumpur International Airport Kuala Lumpur International Airport is the main international airport serving Kuala Lumpur, the capital of Malaysia. It is located in the Sepang District of Selangor, approximately south of downtown Kuala Lumpur and serves the Greater Kuala L ...
in
Malaysia Malaysia is a country in Southeast Asia. Featuring the Tanjung Piai, southernmost point of continental Eurasia, it is a federation, federal constitutional monarchy consisting of States and federal territories of Malaysia, 13 states and thre ...
. 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 Established in 1955, the Middlebury Institute of International Studies at Monterey (MIIS), formerly the Monterey Institute of International Studies, located in Monterey, California, is a Postgraduate education, graduate institute and satellite ...
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 (prior to 2022), Russia, North Korea, and Syria. A
Sudan Sudan, officially the Republic of the Sudan, is a country in Northeast Africa. It borders the Central African Republic to the southwest, Chad to the west, Libya to the northwest, Egypt to the north, the Red Sea to the east, Eritrea and Ethiopi ...
ese pharmaceutical facility, the Al-Shifa pharmaceutical factory, 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 , image = Flag of Jihad.svg , caption = Jihadist flag, Flag used by various al-Qaeda factions , founder = Osama bin Laden{{Assassinated, Killing of Osama bin Laden , leaders = {{Plainlist, * Osama bin Lad ...
. 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 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 (Cut Holes And Sink 'Em) program, in which old ships were filled with chemical weapons stockpiles and then scuttled. CHASE 8 was conducted on June 15, 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, sometimes referred to by its initials A.C., is a Jersey Shore seaside resort city (New Jersey), city in Atlantic County, New Jersey, Atlantic County, in the U.S. state of New Jersey. Atlantic City comprises the second half of ...
.
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 in the North Pacific with other incineration plants following at Deseret Chemical Depot, Pine Bluff Arsenal, Umatilla Chemical Depot and Anniston Army Depot with the last of the VX inventory at these facilities destroyed on December 24, 2008. After 2008 the United States' only remaining stockpile of chemical weapons was located at the Blue Grass Army Depot in
Kentucky Kentucky (, ), officially the Commonwealth of Kentucky, is a landlocked U.S. state, state in the Southeastern United States, Southeastern region of the United States. It borders Illinois, Indiana, and Ohio to the north, West Virginia to the ...
, which housed the last stockpiles of sarin (GB),
mustard gas Mustard gas or sulfur mustard are names commonly used for the organosulfur compound, organosulfur chemical compound bis(2-chloroethyl) sulfide, which has the chemical structure S(CH2CH2Cl)2, as well as other Chemical species, species. In the wi ...
(H) and VX. The Blue Grass stockpile consisted of 101,764 warheads and canisters containing a total of 523 tons of chemical agents loaded onto M55 (rocket), M104 155 mm caliber
howitzer The howitzer () is an artillery weapon that falls between a cannon (or field gun) and a mortar. It is capable of both low angle fire like a field gun and high angle fire like a mortar, given the distinction between low and high angle fire break ...
and M426 8-inch shell artillery shells. Efforts to destroy these agents began in 2019, with the goal of eliminating the United States entire stockpile of chemical weapons by September 30, 2023. The
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
announced in September of 2022 that the last of the United States' stockpile of VX gas had been destroyed, confirming that the last VX rocket was dismantled and destroyed on April 19, 2022.


Stockpile elimination

Worldwide, VX disposal has continued since 1997 under the mandate of 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 ...
. 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 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
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 ...
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 in Kentucky, part of the
Program Executive Office, Assembled Chemical Weapons Alternatives The Program Executive Office, Assembled Chemical Weapons Alternatives (PEO ACWA) was responsible for the safe and environmentally sound destruction of chemical weapons stockpiles previously stored at the Blue Grass Army Depot in Kentucky, and the ...
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 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. The last of the United States remaining stockpile of chemical agents was destroyed on July 7, 2023 with President Biden issuing a press statement that the last of the United States' chemical weapons had been destroyed. The United States was the last of the eight countries that signed the Chemical Weapons Convention to destroy its entire stockpile, this was due to adhering to higher safety protocols than other countries, the government wanted to ensure the protection of both the public and the workers above all, which actually put the United States in violation of the treaty as the last of the stockpile was destroyed after the deadline; the United States' stockpile was the last stockpile of chemical weapons in the world. Although the destruction of the stockpiles does not make the world completely free of chemical weapons, there are nations that have used chemical weapons covertly in recent years like
Syria Syria, officially the Syrian Arab Republic, is a country in West Asia located in the Eastern Mediterranean and the Levant. It borders the Mediterranean Sea to the west, Turkey to Syria–Turkey border, the north, Iraq to Iraq–Syria border, t ...
deploying chlorine gas during the Syrian civil war, Russia has used chemical agents for assassinations and
North Korea North Korea, officially the Democratic People's Republic of Korea (DPRK), is a country in East Asia. It constitutes the northern half of the Korea, Korean Peninsula and borders China and Russia to the north at the Yalu River, Yalu (Amnok) an ...
's leader
Kim Jong Un Kim Jong Un (born 8 January 1983 or 1984) is a North Korean politician and dictator who has served as supreme leader of North Korea since 2011 and general secretary of the Workers' Party of Korea (WPK) since 2012. He is the third son of Kim ...
used a VX-based nerve agent to kill his half brother Kim Jong-nam.


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, officially the City and County of San Francisco, is a commercial, Financial District, San Francisco, financial, and Culture of San Francisco, cultural center of Northern California. With a population of 827,526 residents as of ...
from the island of Alcatraz. The film uses artistic license, 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. Other references to VX are found in the 2012 film ''It's a Disaster'' in which it is revealed that a nearby dirty bomb 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 steals VX nerve gas from Chechen Republic of Ichkeria, Chechen separatists on their way to Syria. Also season 5 of the TV series ''24 season 5, 24'', has a similar storyline.24 - Day 5: 12:00 p.m.-1:00 p.m.
January 30, 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 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'' by the industrial music, industrial band Skinny Puppy contains a song about chemical weapons called "VX Gas Attack". The album ''Warhead'' by electronic-industrial band Phosgore contains a song titled "VX," using audio samples describing the nerve agent. In the BBC show ''Spooks (TV series), Spooks'', series 2 episode 5, a dirty bomb using VX is said to have gone off in a "training exercise". Artistic license is also used in this story, as VX is described as a gas, with "chlorine bonding" making it "almost indestructible." An incorrect formula is given, showing a diester rather than a thioester. In the video game ''Everybody's Gone to the Rapture'', 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 Series, VX plays a major role, as it is used by terrorists in an attempt to kill over half of the British government. In the book ''Ice Cold'', the eighth Rizzoli and Isles novel by Tess Gerritsen, VX gas is featured and responsible for many deaths. The second episode of the TV series ''SEAL Team (TV series), Seal Team'' (season 1) focuses on a chemical weapons lab in an abandoned hospital, producing VX gas. In the Netflix show ''Designated Survivor (TV series), Designated Survivor'', agent Hannah Wells is killed by VX in season 3, episode 7. In the CBS show ''MacGyver (2016 TV series), MacGyver'', season 2 episode 9, a VX canister is the main plot point. In the 2003 video game ''Tom Clancy's Rainbow Six 3: Raven Shield'', the acquisition of VX by terrorists is a major plot point in both versions of the game. In the Crackle (streaming service), Crackle show ''StartUp (TV series), Startup'', American soldiers discover a computer used by apparent terrorists in Aleppo, Aleppo, Syria. "VX components" are displayed as an item for purchase on the computer, which is logged into Araknet, a dark web created by the protagonists of the series. Metal Gear includes references to VX nerve gas in its plotlines, often as a lethal chemical threat within its espionage and warfare scenarios.


See also

* Dugway sheep incident * EA-1763 * EA-2192 * List of Rainbow Codes * Novichok agent


References


External links


VX
at Molecules of the Month, Chemistry IT Centre of the University of Oxford

€”Terrorism: Questions & Answers, Council on Foreign Relations
CDC Facts About VX

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

VX Factsheet
at CBWInfo

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