vx (nerve agent) vx (nerve agent) vx<rekggjh f name=thiermann15/> sp-(−)-vx enantiomer names preferred iupac name s- o-ethyl methylphosphonothioate other names -o-ethyl methylphosphonothioate ethyl (methyl)phosphinateethyl n-2-diisopropylaminoethyl methylphosphonothiolate identifiers cas number 50782-69-9 y 3d model (jsmol) interactive imageinteractive image chebi chebi:136185 n chembl chembl483105 y chemspider 36386 y mesh vx pubchem cid 39793 unii 9a4381183b y comptox dashboard (epa) dtxsid80866161 inchi inchi=1s/c11h26no2ps/c1-7-14-15(6,13)16-9-8-12(10(2)3)11(4)5/h10-11h,7-9h2,1-6h3 ykey: jjiucejqjxnmhv-uhfffaoysa-n yinchi=1/c11h26no2ps/c1-7-14-15(6,13)16-9-8-12(10(2)3)11(4)5/h10-11h,7-9h2,1-6h3key: jjiucejqjxnmhv-uhfffaoyav smiles ccop(c)(=o)sccn(c(c)c)c(c)co=p(occ)(sccn(c(c)c)c(c)c)c properties chemical formula c11h26no2ps molar mass 267.37 g·mol−1 density 1.0083 g cm−3 melting point −51 °c (−60 °f; 222 k) boiling point 300 °c (572 °f; 573 k) log p 2.047 vapor pressure 0.09 pa hazards nfpa 704 (fire diamond) 4 1 1 flash point 159 °c (318 °f; 432 k) lethal dose or concentration (ld, lc): ld50 (median dose) 7 μg/kg (intravenous, rat) except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references part of a series onchemical agents lethal agents blood cyanogen chloride (ck) hydrogen cyanide (ac) arsine (sa) blister ethyldichloroarsine (ed) methyldichloroarsine (md) phenyldichloroarsine (pd) lewisite (l) mustard gas(hd h ht hl hq) nitrogen mustardhn1hn2hn3 nerve g-agents tabun (ga) sarin (gb) chlorosarin (gc) soman (gd) ethylsarin (ge) cyclosarin (gf) gv v-agents ea-3148 v-sub x/gd-7, ve vg vm vp vr vs vx novichok agents a-230 a-232 a-234 a-242 a-262 c01-a035 c01-a039 c01-a042 nettle phosgene oxime (cx) c01-a035 c01-a039 pulmonary/choking chlorine chloropicrin (ps) phosgene (cg) diphosgene (dp) disulfur decafluoride vomiting adamsite chloropicrin diphenylchlorarsine diphenylcyanoarsine diphenylamincyanoarsine incapacitating agents agent 15 (bz) dimethylheptylpyran (dmhp) ea-3167 kolokol-1 pava spray sleeping gas riot-control (rcas) xylyl bromide pepper spray (oc) cs cn (mace) cr list of chemical warfare agents vx is an extremely toxic synthetic chemical compound in the organophosphorus class, specifically, a thiophosphonate. in the class of nerve agents, it was developed for military use in chemical warfare after translation of earlier discoveries of organophosphate toxicity in pesticide research. in recent years, vx was found to be the agent used in the assassination of kim jong-nam. 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 by ranajit ghosh in england during the early 1950s based on research first done by gerhard schrader, a chemist working for ig farben in germany during the 1930s. it is now one of a broader v-series of agents which are classified as nerve agents and have been used as a chemical weapon 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, another nerve agent with a similar mechanism of action. on such exposure, these agents severely disrupt the body's signaling between the nervous and muscular systems, leading to a prolonged neuromuscular blockade, flaccid paralysis of all the muscles in the body including the diaphragm, and death by asphyxiation. 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 due to these physical and biochemical characteristics. as a chemical weapon, it is categorized as a weapon of mass destruction by the united nations and is banned by the chemical weapons convention of 1993, where production and stockpiling of vx exceeding 100 grams (3.53 oz) 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 10 kg (22 lb) 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 298 °c (568 °f), and a freezing point of −51 °c (−60 °f). 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 of 0.09 pascals (1.3×10−5 psi) 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 or talc thickening agent. mechanism of action vx is an acetylcholinesterase inhibitor. it blocks the function of the enzyme acetylcholinesterase (ache). normally, when a motor neuron is stimulated, it releases the neurotransmitter acetylcholine (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 and choline 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 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. accumulation of acetylcholine in the brain also causes neuronal excitotoxicity, due to activation of nicotinic receptors and glutamate 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 phosphonylation 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 near atomic resolution by x-ray crystallography 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 at its phosphorus atom. the individual enantiomers are identified as sp-(−)-vx, and rp-(+)-vx (where the "p" subscript highlights that the chirality is at phosphorus). vx is produced via the transester process, which gives a racemic mixture of the two enantiomers. this entails a series of steps whereby phosphorus trichloride is methylated to produce methyl phosphonous dichloride. the resulting material is reacted with ethanol to form a diester. this is then transesterified with n,n-diisopropylaminoethanol to produce the mixed phosphonite. 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 isopropyl aminoethylmethyl phosphonite (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 organophosphorus nerve agents, vx may be destroyed by reaction with strong nucleophiles. the reaction of vx with concentrated aqueous sodium hydroxide results in two competing solvolysis 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 anion (hydroperoxidolysis) leads to exclusive cleavage of the p–s bond and a more rapid overall reaction. p–s cleavage (non-toxic products) p-o cleavage (ea-2192 product is still toxic) medical aspects further information: nerve agent § biological effects 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 (runny nose) and/or tightness in the chest with shortness of breath (bronchial constriction). miosis (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 (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 5–10 mg (0.00035 oz), 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 and pralidoxime (2-pam), and in the case of convulsions an injected sedative/antiepileptic such as diazepam. 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 receptors (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 moiety from vx to the active site 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 ethyl methylphosphonic acid. r1 = ethyl, r2 = hydrogen, r3 = methyl. controlled studies in humans have shown that minimally toxic doses cause 70–75% depression of erythrocyte cholinesterase 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 further information: nerve agent § 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 discovery occurred when the chemists were investigating a class of organophosphate compounds (organophosphate esters of substituted aminoethanethiols). like gerhard schrader, an earlier investigator of organophosphates, ghosh found that they were quite effective pesticides. in 1954, ici put one of them on