VX (nerve agent)
SP-(−)-VX enantiomer
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Names | |
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Preferred IUPAC name
S-{2-[Di(propan-2-yl)amino]ethyl} O-ethyl methylphosphonothioate | |
Other names
[2-(Diisopropylamino)ethyl]-O-ethyl methylphosphonothioate
Ethyl {[2-(diisopropylamino)ethyl]sulfanyl}(methyl)phosphinate Ethyl N-2-diisopropylaminoethyl methylphosphonothiolate | |
Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
MeSH | VX |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C11H26NO2PS | |
Molar mass | 267.37 g·mol−1 |
Appearance | amber liquid |
Odor | odourless |
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) | |
Flash point | 159 °C (318 °F; 432 K)[3] |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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7 μg/kg (intravenous, rat)[2] |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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VX is an extremely toxic
VX, short for "venomous agent X",
The substance is extremely deadly; VX fatalities occur with exposure to tens of milligram quantities via inhalation or absorption through skin; VX is more potent than
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
Physical properties
VX is an odorless and tasteless[15][16] chiral organophosphorous chemical with a molecular weight of 267.37 g/mol.[17] 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).[18] Its density is similar to that of water.[19] It has a log P value of 2.047, meaning it is relatively hydrophobic with about 100-fold more partitioning into octanol, over water.[20] 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.[21]
When weaponized, it can be dispersed as a liquid, aerosol or as a mixture with a clay or talc thickening agent.[21]
Mechanism of action
VX is an acetylcholinesterase inhibitor.[22] It blocks the function of the
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).[25] 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.[26]
The reaction products of acetylcholinesterase with VX before and after the "aging" reaction were solved in near atomic resolution by X-ray crystallography to aid in antidote development.[27][28] 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
VX is produced via the
, a mixed phosphonite. Finally, this immediate precursor is reacted with sulfur to form VX.VX can also be delivered in
Solvolysis
Like other
Medical aspects
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 (runny nose) and 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.[32]
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.[5] 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 duration of time exposed, is estimated to be 10–15 mg·min/m3 for VX at an exposure time of two minutes and a minute-volume of respiration of 15 L (minute-volume of 15 L corresponds to slight physical activity, i.e., slow walking).[33][34][5]
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.[35][36][37]
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 or antiepileptic such as diazepam.[38] 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.[32]
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.[citation needed] 2-PAM reactivates the acetylcholinesterase enzyme (AChE), thus reversing the effects of VX.[citation needed] 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.[citation needed] Pralidoxime (2-PAM) removes this phosphate group.[citation needed]
Diagnostic tests
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.[39]
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.[citation needed] 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.[citation needed]
The discovery occurred when the chemists were investigating a class of
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.[42]
Use as a weapon
In 1988, a United Nations inquiry established that Cuba was responsible for deploying VX against Angolan insurgents during the Angolan Civil War.[43][44] 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.[43] Patients demonstrating symptoms of exposure to nerve agents first began appearing in Angolan hospitals around 1984.[45]
There was evidence of a combination of chemical agents having been used by
In December 1994 and January 1995,
On 13 February 2017,
Worldwide stockpiles
Some countries known to possess VX are the United States, Russia,
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 15 June 1967, in which the steamship Cpl. Eric G. Gibson was filled with 7,380 VX rockets and scuttled in 2,200 m (7,200 ft) of water off the coast of Atlantic City, New Jersey. Incineration 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 destroyed on 24 December 2008.[57]
Stockpile elimination
Worldwide, VX disposal has continued since 1997 under the mandate of the Chemical Weapons Convention. When the convention entered force, the parties declared worldwide stockpiles of 19,586 tonnes (21,590 short tons) of VX. As of December 2015, 98% of the stockpiles had been destroyed.[58]
In fiscal year 2008, the
The Newport Chemical Depot 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.[60]
The remaining VX stockpile in the U.S. was treated by the
In Russia, the U.S. provided support for these destruction activities with the
In popular culture
One of the best-known references to VX in popular culture is its use in the 1996 film
Other references to VX are found in the 2012 film
The album
In the BBC 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, 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 (season 1) focuses on a chemical weapons lab in an abandoned hospital, producing VX gas.
In the Netflix show Designated Survivor, agent Hannah Wells is killed by VX in season 3, episode 7.
In the CBS show 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
See also
- Dugway sheep incident
- EA-1763
- EA-2192
- List of Rainbow Codes
- Novichok agent
References
- ^ ISBN 978-0128004944. Retrieved March 22, 2017.)
{{cite book}}
: CS1 maint: multiple names: authors list (link - ^ a b Chambers, Michael. "Substance Name: VX". ChemIDplus. U.S. National Library of Medicine, National Institutes of Health. Retrieved 24 February 2017.
- ^ "Material Safety Data Sheet: Nerve Agent (VX)". ilpi.com. Interactive Learning Paradigms Incorporated. December 22, 2000 [1998]. Retrieved October 25, 2007.
- ^ "CDC | Facts About VX". emergency.cdc.gov. Centers for Disease Control and Prevention. Archived from the original on 2018-03-07. Retrieved 2018-03-20.
- ^ a b c FAS Staff (2013). "Types of Chemical Weapons: Nerve Agents [Table. Toxicological Data]". Washington, D.C.: Federation of American Scientists [FAS]. Archived from the original on November 26, 2016. Retrieved March 22, 2017.
- ^ "Nerve Agent VX | U.S. Army Chemical Materials Activity". Retrieved 2023-11-04.
- .
- PMID 32506210.
- ISSN 0362-4331. Retrieved 2023-11-04.
- ISSN 0362-4331. Retrieved 2023-11-04.
- ^ a b Sidell, Frederick R. (1997). "Chapter 5: Nerve Agents" (PDF). Medical Aspects of Chemical and Biological Warfare. p. 142ff.
- ^ Takafuji, Ernest T.; Kok, Allart B. (1997). "Chapter 4: The Chemical Warfare Threat and the Military Healthcare Provider" (PDF). Medical Aspects of Chemical and Biological Warfare. p. 123.
Given favorable weather conditions, the use of persistent agents such as mustard and VX may pose a threat for many days. Such agents can deny or interfere with enemy occupation of terrain or use of equipment
- ^ "Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction. Annex on Chemicals". United Nations Organisation for the Prohibition of Chemical Weapons.
- ^ OPCW (2005). "Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction" (PDF). OPCW.org. Organization for the Prohibition of Chemical Weapons (OPCW). p. 122. Retrieved 26 August 2016.
- ^ "CDC | Facts About VX". emergency.cdc.gov. 2019-05-16. Retrieved 2022-04-27.
- ISSN 0362-4331. Retrieved 2022-04-27.
- ^ PubChem. "O-Ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-04-27.
- ^ "Tx 60 | C11H26NO2PS". PubChem. Retrieved 2017-04-13.
- ^ "Tx 60 | C11H26NO2PS". PubChem. Retrieved 2017-04-13.
- ^ "Tx 60 | C11H26NO2PS". PubChem. Retrieved 2017-04-13.
- ^ a b Croddy, Eric (October 1, 2002). "Dusty Agents and the Iraqi Chemical Weapons Arsenal". Nuclear Threat Initiative [NTI]. Washington, DC and Monterey, California: Middlebury Institute of International Studies, James Martin Center for Nonproliferation Studies. Retrieved March 22, 2017 – via NTI.org.
- ^ McDowall, Jennifer (November 2005). "Acetylcholine Recepetors". European Molecular Biology Laboratory/European Bioinformatics Institute.
- ^ Rash, John; Elmund, Julie (July 7, 1988). "Pathophsyiology of Anticholinesterase Agents" (PDF). Colorado State University Department of Anatomy and Neurobiology. Archived (PDF) from the original on April 12, 2022.
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- ISBN 978-0-8493-1434-6. Retrieved 2014-02-21.
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- ^ a b "US Army Toxic Chemical Agent Safety Standards" (PDF). DA PAM 385-61. Section 7-8 Self/Buddy Aid Procedures. US Army. Archived from the original (PDF) on December 24, 2003. Retrieved December 15, 2007.
- ISBN 9780429632969.
- ^ Toxicology, National Research Council (US) Committee on (1997). Review of Acute Human-Toxicity Estimates for VX. National Academies Press (US).
- ^ "CDC | Facts About VX". emergency.cdc.gov. 2019-05-16. Retrieved 2019-12-22.
- ^ "ATSDR - Medical Management Guidelines (MMGs): Nerve Agents (GA, GB, GD, VX)". www.atsdr.cdc.gov. Retrieved 2019-12-22.
- ^ "Facts About Nerve Agents". www.health.ny.gov. Retrieved 2019-12-22.
- ^ "VX Recognition and Treatment" (PDF). Physicians for Human Rights. Retrieved December 14, 2019.
- ^ R. Baselt (2017). Disposition of Toxic Drugs and Chemicals in Man (11th ed.). Seal Beach, CA: Biomedical Publications. pp. 2264–65.
- ^ Ghosh, R.; Newman, J.E. (Jan 29, 1955). "A new group of organophosphorus pesticides". Chemistry and Industry: 118.
- ^ Usborne, Tim (2016-06-28), Inside Porton Down: Britain's Secret Weapons Research Facility, Michael Mosley, Jonathan Lyle, Rob Evans, retrieved 2018-03-20
- ^ Kazuo K. Kimura, Bernard P. McNamara, Van M. Sim (1960-07-01). "Intravenous Administration of VX in Man". Archived from the original on March 26, 2017. Retrieved 2017-03-25.
{{cite web}}
: CS1 maint: multiple names: authors list (link) - ^ ISBN 978-0-8173-1837-6. Retrieved October 11, 2014.
- Washington D.C.: Government Printing Office. 2002. p. 22. Retrieved 28 March 2018.
Already in 1988, the United Nations Security Council has been informed of use of toxic weapons by Soviet-supported Cuba in Angola. Belgian toxicologists had certified that residue of chemical weapons—including sarin and VX gas—had been found in plants, water and soil where Cuban troops were alleged to have used chemicals against Savimbi's troops.
- ^ "Cubans using poison gas in Angola". The Lewiston Journal. Lewiston–Auburn, Maine. August 26, 1988. Retrieved July 28, 2015.
- ^ BBC (March 16, 1988). "1988: Thousands die in Halabja gas attack". Retrieved March 1, 2012.
- ^ CIA (May 2, 2007). "Intelligence Update: Chemical Warfare Agent Issues Chemical Warfare Issues During the Persian Gulf War". Archived from the original on June 13, 2007. Retrieved Oct 22, 2012.
- ^ Pamela Zurer. "Japanese cult used VX to slay member". Chemical and Engineering News. 1998, Vol 76 (no. 35), 7.
- ISSN 0362-4331. Retrieved 2017-02-24.
- ^ "Kim Jong-nam killing: VX nerve agent 'found on his face'". BBC News. 24 February 2017. Retrieved 2017-02-24.
- ^ One suspect in Kim Jong Nam murder suffered effects of VX agent. The Star. 2017-2-24. Retrieved 23 February 2017.
- ^ McCurry, Justin (2017-02-20). "What is the VX nerve agent that killed North Korean Kim Jong-nam?". The Guardian. Retrieved 2017-02-25.
- ^ "VX". Council on Foreign Relations. Archived from the original on January 31, 2009. Retrieved June 12, 2007.
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- ^ "VX Destruction Milestone". U.S. Army Chemical Materials Agency. March 20, 2009. Archived from the original on 2009-03-27.
- ^ "Annex 3". Report of the OPCW on the Implementation of the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction in 2015 (Report). Organisation for the Prohibition of Chemical Weapons. 30 November 2016. p. 42. Retrieved 8 March 2017.
- ^ "App_Q_Sea_Disposal_final" (PDF). denix.osd.mil. Retrieved September 7, 2009.
- U.S. Army Chemical Materials Agency. Retrieved January 7, 2013.
- ^ Schneidmiller, Chris (April 18, 2001). "U.S. Chemical Weapons Disposal Slippage "No Surprise," Expert Says". Nuclear Threat Initiative. Retrieved Oct 11, 2012.
- USSTRATCOM Center for Combating WMD. Retrieved 23 May 2012.
- ^ Levy, Clifford J. (May 27, 2009). "In Siberia, the Death Knell of a Complex Holding a Deadly Stockpile". The New York Times. Retrieved April 9, 2010.
- ^ "Molecular dynamics to combat chemical terrorism". Chemistry World. Royal Society of Chemistry. 31 January 2012.
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- ^ 24 - Day 5: 12:00 p.m.-1:00 p.m., 30 January 2006.
External links
- VX at Molecules of the Month, Chemistry IT Centre of the University of Oxford
- Questions and Answers for VX—Terrorism: Questions & Answers, Council on Foreign Relations
- CDC Facts About VX
- U.S. Army's Chemical Materials Agency (CMA)
- VX Factsheet at CBWInfo
- Decommissioning Surplus VX – Article from The New York Times