Editing Soman

{{short description|Chemical compound (nerve agent)}}
{{cs1 config|name-list-style=vanc}}
{{Other uses}}
{{chembox
| Verifiedfields = changed
| verifiedrevid  = 418119696
| ImageFile1     = Soman-3D-balls-by-AHRLS-2011.png
| ImageClass1 = bg-transparent
| ImageSize1     = 200px
| Name           = Soman
| ImageFile      = Soman-2D-by-AHRLS-2011.png
| ImageClass = skin-invert-image
| ImageSize      = 160px
| PIN            = 3,3-Dimethylbutan-2-yl methylphosphonofluoridate
| OtherNames     = <small>GD; Phosphonofluoridic acid, methyl-, 1, 2, 2-trimethylpropyl ester; 2-(Fluoromethylphosphoryl)oxy-3,3-dimethylbutane; Pinacolyl methylphosphonofluoridate; 1,2,2-Trimethylpropyl methylphosphonofluoridate; Methylpinacolyloxyfluorophosphine oxide; Pinacolyloxymethylphosphonyl fluoride; Pinacolyl methanefluorophosphonate; Methylfluoropinacolylphosphonate; Fluoromethylpinacolyloxyphosphine oxide; Methylpinacolyloxyphosphonyl fluoride; Pinacolyl methylfluorophosphonate; 1,2,2-Trimethylpropoxyfluoromethylphosphine oxide</small>
| Section1       = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 7032
| InChI = 1/C7H16FO2P/c1-6(7(2,3)4)10-11(5,8)9/h6H,1-5H3
| InChIKey = GRXKLBBBQUKJJZ-UHFFFAOYAY
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 15910
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H16FO2P/c1-6(7(2,3)4)10-11(5,8)9/h6H,1-5H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GRXKLBBBQUKJJZ-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 96-64-0 <!-- mixture of stereoisomers -->
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3OF3WXB67Q
| PubChem = 7305
| SMILES = FP(=O)(C)OC(C)C(C)(C)C
}}
| Section2       = {{Chembox Properties
| C=7 | H=16 | F=1 | O=2 | P=1
| Appearance = When pure, colorless liquid with odor resembling rotten fruit. With impurities, amber or dark brown, with odor of camphor oil.
| Density = 1.022 g/cm<sup>3</sup>
| MeltingPtC = -42
| BoilingPtC = 198
| Solubility = Moderate
| VaporPressure = 0.40 mmHg (53 Pa)
}}
| Section3       = {{Chembox Hazards
| MainHazards = Highly Toxic
| FlashPt = 
| AutoignitionPt = 
| NFPA-H = 4
| NFPA-F = 1
| NFPA-R = 1
| NFPA-S = 
}}
}}

'''Soman''' (or '''GD''', '''EA 1210''', '''Zoman''', '''PFMP''', '''A-255''', systematic name: ''O''-pinacolyl methyl{{shy}}phos{{shy}}phono{{shy}}fluoridate)<ref>[http://www.gulfweb.org/bigdoc/report/appgd.html] {{Webarchive|url=https://web.archive.org/web/20130912230529/http://www.gulfweb.org/bigdoc/report/appgd.html |date=2013-09-12 }} United States Senate, 103d Congress, 2d Session. (May 25, 1994). Material Safety Data Sheet -- Lethal Nerve Agents Somain (GD and Thickened GD). Retrieved Nov. 6, 2004.</ref> is an extremely toxic chemical substance. It is a [[nerve agent]], interfering with normal functioning of the mammalian [[nervous system]] by inhibiting the  enzyme [[cholinesterase|cholin{{shy}}esterase]]. It is an inhibitor of both [[acetylcholinesterase|acetyl{{shy}}cholin{{shy}}esterase]] and [[butyrylcholinesterase|butyryl{{shy}}cholin{{shy}}esterase]].<ref>{{cite journal  |vauthors=Millard CB, Kryger G, Ordentlich A |display-authors=etal |title=Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level |journal=Biochemistry |volume=38 |issue=22 |pages=7032–9 |date=June 1999 |pmid=10353814 |doi=10.1021/bi982678l|s2cid=11744952 }}</ref> As a [[chemical weapon]], it is classified as a [[weapon of mass destruction]] by the [[United Nations]] according to [[UN Resolution 687]]. Its [[Chemical weapon proliferation|production]] is strictly controlled, and stockpiling is outlawed by the [[Chemical Weapons Convention]] of 1993 where it is classified as a [[List of Schedule 1 substances (CWC)|Schedule 1 substance]]. Soman was the third of the so-called ''G-series'' nerve agents to be discovered along with [[tabun (nerve agent)|GA]] (tabun), [[sarin|GB]] (sarin), and [[cyclosarin|GF]] (cyclosarin).

When pure, soman is a [[Volatility (chemistry)|volatile]], corrosive, and colorless liquid with a faint odor like that of mothballs or rotten fruit.<ref name=":2">{{Cite web|url=https://emergency.cdc.gov/agent/soman/basics/facts.asp|title=CDC {{!}} Facts About Soman|website=emergency.cdc.gov|publisher=Centers for Disease Control and Prevention|language=en-us|archive-url=https://web.archive.org/web/20171222122436/https://emergency.cdc.gov/agent/soman/basics/facts.asp|archive-date=2017-12-22|url-status=live|access-date=2018-03-20}}</ref> More commonly, it is a yellow to brown color and has a strong odor described as similar to [[camphor]]. The [[LD50|LCt<sub><span style="font-size:100%;">50</span></sub>]] for soman is 70{{nbs}}mg·min/m<sup>3</sup> in humans. 

GD can be [[thickening|thickened]] for use as a chemical spray using an acryloid copolymer. It can also be deployed as a [[binary chemical weapon]]; its precursor chemicals are [[methylphosphonyl difluoride|methyl{{shy}}phos{{shy}}phonyl difluoride]] and a mixture of [[pinacolyl alcohol]] and an [[amine]].{{cn|date=October 2024}}

== History ==
After World War I, during which [[mustard gas]] and [[phosgene]] were used as chemical warfare agents, the 1925 [[Geneva Protocol]] was signed in an attempt to ban chemical warfare. Nevertheless, research into chemical warfare agents and the use of them continued. In 1936 a new, more dangerous chemical agent was discovered when  [[Gerhard Schrader]] of [[IG Farben]] in Germany isolated [[Tabun (nerve agent)|tabun]] (named GA for German Agent A by the United States), the first nerve agent, while developing new [[insecticide]]s. This discovery was followed by the isolation of [[sarin]] (designated GB by the United States) in 1938, also discovered by Schrader.

During World War II, research into nerve agents continued in the United States and Germany. In summer 1944, soman, a colorless liquid with a camphor odor (designated GD by the United States), was developed by the Germans. Soman proved to be even more toxic than tabun and sarin. Nobel Laureate [[Richard Kuhn]] together with [[Konrad Henkel]] discovered soman during research into the pharmacology of tabun and sarin at the Kaiser Wilhelm Institute for Medical Research at [[Heidelberg]].<ref>{{Cite journal|last=Schmaltz|first=Florian|date=September 2006|title=Neurosciences and research on chemical weapons of mass destruction in Nazi Germany|journal=Journal of the History of the Neurosciences|volume=15|issue=3|pages=186–209|doi=10.1080/09647040600658229|issn=0964-704X|pmid=16887760|s2cid=46250604}}</ref> This research was commissioned by the German Army. Soman was produced in small quantities at a pilot plant at the [[IG Farben]] factory in [[Ludwigshafen]]. It was never used in World War II.<ref name="Lukey">{{cite book|title=Chemical Warfare Agents: Chemistry, Pharmacology, Toxicology, and Therapeutics|author1=Lukey, Brian J.|author2=Salem, Harry|publisher=CRC Press|year=2007|isbn=9781420046618|pages=10–13}}</ref>

Producing or stockpiling soman was banned by the 1993 [[Chemical Weapons Convention]]. When the convention entered force, the parties declared worldwide stockpiles of 9,057 tonnes of soman. The stockpiles were destroyed by 2018.<ref>{{Cite web |date=2018-11-19 |title=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 2017 |url=https://www.opcw.org/sites/default/files/documents/2018/11/c2304%28e%29.pdf |access-date=2024-02-09 |publisher=Organisation for the Prohibition of Chemical Weapons |page=45}}</ref>

The crystal structure of soman complexed with [[acetylcholinesterase|acetyl{{shy}}cholin{{shy}}esterase]] was determined by Millard et al. in 1999 by X-ray crystal{{shy}}lography: [https://www.rcsb.org/structure/1som 1som]. Other solved acetyl{{shy}}cholin{{shy}}esterase structures with soman bound to them include [https://www.rcsb.org/structure/2wfz 2wfz], [https://www.rcsb.org/structure/2wg0 2wg0] and [https://www.rcsb.org/structure/2wg1 2wg1].

==Structure and reactivity==
[[File:Soman Structural Formulae Stereoisomers V.1.svg|left|thumb|260x260px|The stereoisomers of soman.]]
Soman (C(±)P(±)-soman) has four [[Stereoisomerism|stereoisomers]], each with a different toxicity, though largely similar. The stereoisomers are C(+)P(+)-soman, C(+)P(−)-soman C(−)P(−)-soman and C(−)P(+)-soman.<ref>{{Cite journal|date=1998-07-01|title=Inhalation Toxicokinetics of Soman Stereoisomers in the Atropinized Guinea Pig with Nose-Only Exposure to Soman Vapor|journal=Toxicology and Applied Pharmacology|language=en|volume=151|issue=1|pages=79–87|doi=10.1006/taap.1998.8451|pmid=9705889|issn=0041-008X|last1=Langenberg|first1=Jan P.|last2=Spruit|first2=Helma E.T.|last3=Van Der Wiel|first3=Herma J.|last4=Trap|first4=Henk C.|last5=Helmich|first5=Rob B.|last6=Bergers|first6=Wim W.A.|last7=Van Helden|first7=Herman P.M.|last8=Benschop|first8=Hendrik P.}}</ref><ref>{{Cite journal|date=1988-08-01|title=Hydrolysis of the four stereoisomers of soman catalyzed by liver homogenate and plasma from rat, guinea pig and marmoset, and by human plasma|journal=Biochemical Pharmacology|language=en|volume=37|issue=15|pages=2939–2948|doi=10.1016/0006-2952(88)90279-1|issn=0006-2952|last1=De Jong|first1=Leo P.A.|last2=Van Dijk|first2=Corry|last3=Benschop|first3=Hendrik P.|pmid=3395367}}</ref>

Soman has a phosphonyl group with a fluoride and a (large) hydrocarbon covalently bound to it. The structure is thus similar to that of sarin, which has only a smaller hydrocarbon group attached (isopropyl). Because of the similarity between the chemical structures, the reactivity of the two compounds is almost the same. Soman and sarin will both react using the phospho oxygen group, which can bind to amino acids like serine.

== Synthesis ==
The manufacture of soman is very similar to the manufacture of sarin. The difference is that the [[isopropanol]] from the sarin processes is replaced with [[pinacolyl alcohol]]:
[[File:GD-synthesis-by-AHRLS-2011.png|center|The synthesis of agent GD|thumb|600x600px]]
Soman is synthesized by reacting [[pinacolyl alcohol]] with [[methylphosphonyl difluoride|methyl{{shy}}phos{{shy}}phonyl difluoride]]. The result of this reaction is the forming of soman which is described as “colorless liquid with a somewhat fruity odor.” The low vapor pressure of soman will also produce the volatile gas form of soman. Also, the acid [[hydrogen fluoride]] will form due to the elimination of fluoride and a proton. This acid is indirectly dangerous to humans. Skin contact with hydrogen fluoride will cause an immediate reaction with water which produces [[hydrofluoric acid]].<ref name=Lukey/>

== Mechanisms of action==

Soman is an organo{{shy}}phosphorus nerve agent with a mechanism of action similar to tabun. Nerve agents inhibit [[acetylcholine esterase]] (AChE) by forming an [[adduct]] with the enzyme via a serine residue on that enzyme. These adducts may be decomposed hydrolytically or, for example, by the action of some oximes and thereby regenerate the enzyme. A second reaction type, one in which the enzyme–organo{{shy}}phosphate (OP) complex undergoes a subsequent reaction, is usually described as "aging". Once the enzyme–OP complex has aged it is no longer regenerated by the common, oxime reactivators. The rate of this process is dependent on the OP. Soman is an OP that stimulates the rate of aging most rapidly decreasing the half-life to just a few minutes.

AChE is an enzyme involved with neuro{{shy}}transmission. Because of the severe decrease of the half-life of this enzyme, neuro{{shy}}transmission is abolished in a matter of minutes.<ref name=Lukey/>

==Metabolism==
Once taken up in the human body, soman not only inhibits AChE, but it is also a substrate for other esterases. Reaction of soman with these esterases allows for the detoxication of the compound. No metabolic toxification reactions are known for soman.

Soman can be hydrolyzed by a so-called A-esterase, more specifically a diiso{{shy}}propyl{{shy}}fluoro{{shy}}phosphatase. This esterase, also called somanase, reacts with the anhydride bond between phosphorus and fluorine and accounts for the hydrolysis of the fluoride. Somanase also hydrolyses the methyl group of soman resulting in the formation of pinacolyl methyl{{shy}}phosphonic acid (PMPA), which is a less potent AChE inhibitor.<ref name=":0">{{Cite journal|last=Jokanović|first=M.|date=2001-09-25|title=Biotransformation of organophosphorus compounds|journal=Toxicology|volume=166|issue=3|pages=139–160|issn=0300-483X|pmid=11543910|doi=10.1016/s0300-483x(01)00463-2}}</ref><ref name=":1">{{Cite journal|last=Jokanović|first=Milan|date=2009-07-10|title=Current understanding of the mechanisms involved in metabolic detoxification of warfare nerve agents|journal=Toxicology Letters|volume=188|issue=1|pages=1–10|doi=10.1016/j.toxlet.2009.03.017|issn=1879-3169|pmid=19433263}}</ref>

Soman can also bind to other [[esterase]]s, e.g., [[Acetylcholinesterase|AChE]], [[cholinesterase|cholin{{shy}}esterase]] (ChE) and [[carboxylesterase|carboxyl{{shy}}esterase]]s (CarbE). In this binding, soman loses its fluoride. After binding to AChE or ChE soman also loses its phosphoryl group, leading to the formation of [[methylphosphonic acid|methyl{{shy}}phosphonic acid]] (MPA). Binding to CarbE reduce the total concentration of soman in the blood, thus resulting in a lower toxicity. Furthermore, CarbE are involved in the detoxication by [[Hydrolysis|hydrolysing]] soman to PMPA. So CarbE account for the detoxication of soman in two ways.<ref name=":0" /><ref name=":1" />

The importance of the detoxication of soman after exposure was illustrated in experiments of Fonnum and Sterri (1981). They reported that only 5% of [[Median lethal dose|LD50]] inhibited AChE in rats, resulting in acute toxic effects. This shows that metabolic reactions accounted for the detoxification of the remaining 95% of the dose.<ref>{{cite journal | author = Fonnum, F. |author2 = Sterri, S.H. | year = 1981 | title = Factors modifying the toxicity of organophosphorus compounds including soman and sarin | journal = Fundam. Appl. Toxicol. | volume = 1 | pages = 143–147 | doi = 10.1016/S0272-0590(81)80050-4 | pmid = 7184780 | issue = 2}}</ref>

[[File:Metabolisim of Soman.png|framed|center|The metabolism of soman.]]

==Signs and symptoms==
As soman is closely related to compounds such as sarin, indications for a soman poisoning are relatively similar. One of the first observable signs of a soman poisoning is [[miosis]]. Some, but not all of the later indications are vomiting, extreme muscle pain and peripheral nervous system problems.  Those symptoms show as soon as 10 minutes after exposure and may last for many days.<ref name="informahealthcare">{{Cite journal |doi = 10.3109/15563657408987971|pmid = 4838227|title = Soman and Sarin: Clinical Manifestations and Treatment of Accident of Accidental Poisoning by Organophosphates|journal = Clinical Toxicology|volume = 7|issue = 1|pages = 1–17|year = 1974|last1 = Sidell|first1 = Frederick R.}}</ref>

In addition to the direct toxic effects on the nervous system, people exposed to soman may experience long-term effects, most of which are psychological. Subjects who were exposed to a small dose of soman suffered severe toxic effects; once treated, the subjects often developed depression, had antisocial thoughts, were withdrawn and subdued, slept restlessly and had bad dreams. These symptoms lasted six months after exposure but disappeared without lasting damage.<ref>{{Cite journal|last=Sidell|first=F. R.|date=1974|title=Soman and sarin: clinical manifestations and treatment of accidental poisoning by organophosphates|journal=Clinical Toxicology|volume=7|issue=1|pages=1–17|doi=10.3109/15563657408987971|issn=0009-9309|pmid=4838227}}</ref>

==Toxicity and efficacy==
The [[Median lethal dose|LC<sub>50</sub>]] of soman in air is estimated to be 70&nbsp;mg min per m<sup>3</sup>. Compared with the LC<sub>50</sub> value for a rat, the human lethal concentration is much lower (954.3&nbsp;mg min/m<sup>3</sup> versus 70&nbsp;mg min/m<sup>3</sup>). For compounds such as soman, which may also be used as a weapon, often a fraction of the LC<sub>50</sub> dose is where the first effects appear. [[Miosis]] is one of the first symptoms of soman intoxication and can be seen in doses of less than 1% of the LC<sub>50</sub>.<ref>Bey TA, Sullivan JB, Walter FG (2001) Organophosphate and carbamate insecticides. In: Sullivan JB, Krieger GR (eds) Clinical environmental health
and toxic exposures. Lippincott Williams & Williams, Philadelphia, pp 1046–1057</ref>

==Effects on animals==
Experiments have been done in which rats were exposed to soman to test if behavioral effects could be seen at low doses without generating overt symptoms. Exposure of the rats to soman in a dose of less than 3 percent of the LD<sub>50</sub> caused alterations of the behavior. The active avoidance of the exposed rats was less than the avoidance of non-exposed rats (two-way shuttlebox experiment). Also the motor coordination (hurdle-stepping task), open field behavior and active as well as passive avoidance behavior were affected. One can conclude that rats that are exposed to soman performed with less success in tasks that require motor activity as well as the function of higher structures of the central nervous system (CNS) on the same time. In this, soman has a predominantly central effect.

The knowledge of the effects of low doses of soman and other choline esterase inhibitors on rats could possibly be used to explain the relatively high incidence of airplane accidents due to errors of agricultural pilots. If this knowledge could be applied to humans, one could explain this high incidence with depressed choline esterase activity due to exposure to pesticides. It is not known whether the extrapolation from rats to humans can be made.<ref>{{Cite journal|last1=WOLTHUIS|first1=O. L.|last2=VANWERSCH|first2=R. A. P.|date=1984-04-01|title=Behavioral Changes in the Rat after Low Doses of Cholinesterase Inhibitors|journal=Toxicological Sciences|language=en|volume=4|issue=2part2|pages=195–208|doi=10.1093/toxsci/4.2part2.195|pmid=6724212|issn=1096-6080}}</ref>

== References ==
{{reflist}}

==External links==
* United States Senate, 103d Congress, 2d Session (May 25, 1994). [http://www.gulfweb.org/bigdoc/report/appgd.html Material Safety Data Sheet -- Lethal Nerve Agents Somain (GD and Thickened GD)] ({{Webarchive|url=https://web.archive.org/web/20130912230529/http://www.gulfweb.org/bigdoc/report/appgd.html |date=2013-09-12 }}). Retrieved Nov. 6, 2004.
* [http://proteopedia.org/wiki/index.php/AChE_inhibitors_and_substrates AChE inhibitors and substrates] in [[Proteopedia]]
* [http://proteopedia.org/wiki/index.php/2wfz 2wfz] in [[Proteopedia]] 
* [http://proteopedia.org/wiki/index.php/2wg0 2wg0] in [[Proteopedia]]
* [http://proteopedia.org/wiki/index.php/2wg1 2wg1] in [[Proteopedia]]
* [http://proteopedia.org/wiki/index.php/1som 1som] in [[Proteopedia]]
*  https://somantoxicologia.wixsite.com/meusite {{In lang|pt}}

{{Chemical warfare}}
{{Acetylcholine metabolism and transport modulators}}

[[Category:Acetylcholinesterase inhibitors]]
[[Category:Cold War weapons of the Soviet Union]]
[[Category:G-series nerve agents]]
[[Category:German chemical weapons program]]
[[Category:German inventions of the Nazi period]]
[[Category:Methylphosphonofluoridates]]
[[Category:Pinacolyl esters]]
[[Category:Soviet chemical weapons program]]