Soman

For other uses, see Soman (disambiguation).

Soman
Preferred IUPAC name 3,3-Dimethylbutan-2-yl methylphosphonofluoridate
Other names 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
Identifiers
PubChem	7305
ChemSpider	7032 Y
ChEMBL	CHEMBL15910
Jmol-3D images	Image 1
SMILES FP(=O)(OC(C)C(C)(C)C)C
InChI InChI=1S/C7H16FO2P/c1-6(7(2,3)4)10-11(5,8)9/h6H,1-5H3 Y Key: GRXKLBBBQUKJJZ-UHFFFAOYSA-N Y InChI=1/C7H16FO2P/c1-6(7(2,3)4)10-11(5,8)9/h6H,1-5H3 Key: GRXKLBBBQUKJJZ-UHFFFAOYAY
Properties
Molecular formula	C7H16FO2P
Molar mass	182.17 g mol−1
Appearance	When pure, colorless liquid with fruity odor. With impurities, amber or dark brown, with oil of camphor odor
Density	1.022 g/cm³
Melting point	-42 °C, 231 K, -44 °F
Boiling point	198 °C, 471 K, 388 °F
Solubility in water	Moderate
Vapor pressure	0.40 mmHg (53 Pa)
Hazards
Main hazards	Toxic
NFPA 704	1 4 1
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Soman, or GD (systematic name: O-Pinacolyl methylphosphonofluoridate), is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the cholinesterase enzyme. It is an inhibitor of both acetylcholinesterase and butyrylcholinesterase. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN Resolution 687. Its production is strictly controlled, and stockpiling is outlawed by the Chemical Weapons Convention of 1993 where it is classified as a Schedule 1 substance. Soman was the third of the so-called G-series nerve agents to be discovered along with GA (tabun), GB (sarin), and GF (cyclosarin).

It is a volatile, corrosive, and colorless liquid with a faint odor when pure. More commonly, it is a yellow to brown color and has a strong odor described as similar to camphor. The LCt₅₀ for soman is 70 mg·min/m³ in humans. It is both more lethal and more persistent than sarin or tabun, but less so than cyclosarin.

GD can be 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 and a mixture of pinacolyl alcohol and an amine.

History

After World War I, in which mustard agent and phosgene were used as chemical warfare agents, the Geneva protocol (1925) was signed in an attempt to ban chemical warfare. Nevertheless, research into chemical warfare agents and the use of them continued. It wasn’t until 1936 before new, more dangerous chemical agents were discovered: Dr. Gerhard Schrader (I.G. Farben, Germany) isolated Tabun (named GA for German Agent A by the United States) the first nerve agent while developping new insecticides. 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 the research into nerve agents continued in the United States and Germany. In 1944, Soman, a colourless liquid with a camphor odor, (designated GD by the United States) was developped by the Germans. Soman showed to be even more toxic than Tabun and Sarin. Nobel Laureate Dr. Richard Kuhn discovered Soman during research into the pharmacology of Tabun and Sarin. This research was commisioned by the German Army. Although Soman was produced and stored by the Germans, it was never used in World War II, just like Tabun and Sarin were never used as chemical warfare agents.

The crystal structure of soman complexed with acetylcholinesterase was determined by Millard et al. (1999) by X-ray crystallography (PDB codes: 2wfz, 2wg0, 2wg1, and 1som).

Structure and reactivity

Soman, or 3,3-Dimethylbutan-2-yl methylphosponofluoridate, has a phosphonyl group with a fluoride and a (large) hydrocarbon covalently bound to it. The structure is therefore similiar like Sarin; which only has a smaller hydrocarbon group attached (isopropyl).

Because of the similarity between the chemical structures, the reactivity of both toxines is (almost) the same. Soman and Sarin will both react by 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:

The synthesis of soman from pinacolyl alcohol

Soman is synthesized by reacting pinacolyl alcohol with methylphosphonyl difluoride. The result of this reaction is the forming of Soman (3,3-Dimethylbutan-2-yl methylphosponofluoridate) 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 and inmediate reaction with water which produces hydrofluoric acid.

Available Forms

Soman is a liquid under standard conditions with a somewhat fruity aroma. On the battlefield, it is nebulized and thus not a gaseous substance. Soman has four stereo isomers, each with a different toxicity, though largely similar.

Mechanisms of action

Soman is a organophosphorous 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–OrganoPosphate (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 proces is dependant on the OP. Soman is an OP that stimulates the rate of aging most rapidly decreasing the halflife to just a few minutes.

AChE is an enzyme involved with neurotransmission. Because of the severe decrease of the half-life of this enzyme, neurotransmission is abolished in a matter of minutes.

Metabolism

Once taken up in the human body, soman doesn’t only inhibit AChE, but it is also a substrate for other esterases. Reaction of soman with these esterases allows for the detoxication of the compound. There aren’t any metabolic toxification reactions known for soman.

Soman can be hydrolysed by a so called A-esterase, more specific a diisopropylfluorophosphatase. This esterase, also called somanase, reacts with the anhydride bond between phosphorus and fluor and accounts for the hydrolysis of the fluoride. Somanase also hydrolyses the methyl group of soman resulting in the formation of pinacolyl methylphosphonic acid (PMPA), which is a less potent AChE inhibitor.

Soman can also bind to other esterases, e.g., AChE, cholinesterase (ChE) and carboxylesterases (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 (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 hydrolysing soman to PMPA. So CarbE account for the detoxication of soman in two ways.

The importance of the detoxication of soman after exposure was illustrated in experiments of Fonnum and Sterri (1981). They reported that only 5% of 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.

The metabolisim of soman

Indications

As Soman is closely related to compunds such as Sarin, indications for are Soman poisoning are relatively similar. One of the first observable sings of a soman poisoning is miosis. Some, but not all of the later indications are throwing up, extreme muscle pain and peripheral nervous system problems. Those symptoms show as fast as 10 minutes after exposure and may last for many days.

Toxicity and efficacy

Soman is a very effective compund, raising problems with very little doses. The LC50 of soman in air is 70 mg min per m³. For compounds such as soman, which may also be used as a weapon, oftenly the fraction of the LC50 dosis where the first effect shows, is noted. Miosis, is one of the first symptoms of soman intoxication and already shows on a dosis less than 1% of the LC50.

By using animal models, it is able to predict the LD50 value of Soman (GD). Table 1 shows LD50 values of several exposed organisms via different administration routes. Most LD50 values via the same administration route give somewhat different lethal doses, which means the organisms metabloize the compounds differently.

There is an estimate of the LCt50 value for humans, which is determined at 70 mg min/m³. Compared with the LCt50 value of a rat, the human lethal concentration is much lower (954.3 mg min/m³ versus 70 mg min/m³).

Side effects

Exept for the direct toxic effects concerning the nervous system, people exposed to soman might experience some long term effects, most of which are psychological.

People that were exposed to a very little dose of soman suffered severe toxic effects, once those were treated and long gone the same persons often developed a depression, admitted they had antisocial thoughts, were withdrawn and subdued, slept restlessly and had bad dreams. Those symptomes lasted until half a year after exposure but left without any life long damages.

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 LD50 caused alterations of the behaviour.. 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 behaviour and active as well as passive avoidance behaviour 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 air plane 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. Wether the extrapolation from rats to humans can be made is unknown.

External links

• 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.
• AChE inhibitors and substrates in Proteopedia
• 2wfz in Proteopedia
• 2wg0 in Proteopedia
• 2wg1 in Proteopedia
• 1som in Proteopedia