Hydrolysis of tabun

This material is a precursor for some G-series, GV-series, and V-series nerve agents and is also commonly found as a decomposition product/impurity resulting from hydrolysis of Tabun (C01-A001). 

This material is commonly found as a degradation product from hydrolysis of Tabun (C01-A001). 

Hoskin, F.C.G. and G.S. Trick. 1955. Stereospecificity in the enzymatic hydrolysis of tabun and acetyl-B-methylcholine chloride. Can. T. Biochem. Physiol. 3 963-969. 

Base-induced hydrolysis (and direct water hydrolysis) of tabun has been studied (Sanchez et al., 1993 McNaughton and Brewer, 1994). Analyzed by GC-MS, a number of previously unrecognized materials have been observed (D Agostino and Provost, 1992). Larsson (1952) has reported a spectrophotometric study of tabun hydrolysis. 

Benes, J. 1963. Kinetics of the hydrolysis of tabun in acid solutions. Acta Chemica Scandinavica, 17 1783-1785. 

The (+)-isomer is obtained similarly by the use of a phosphorylphosphatase. The stereoselectivity of the hydrolysis of tabun enantiomers by phosphorylphosphatases is species dependent. It was observed that incubation with rat plasma was the only method that produced (+)-tabun with adequate optical purity (92-99% ee). 

There is a considerable amount of published data available on the hydrolysis of tabun, its analogues and the organophosphorus fluoridates. However, the variation in experimental conditions under which the data were measured, and in some instances the contradictory nature of the data, make direct comparisons of rate data difficult. Some second-order rate coefficients for the basic hydrolysis of nerve agents are given in Table 2. 

B. 0. Holmstead1 has carried out investigations on the rate of hydrolysis of cyano-phosphorus compounds. First of all, mention may be made of the hydrolysis of diethyl phosphorocyanidate2 which proceeds rapidly in a buffer solution at pH 7-2 giving rise to the CN ion. Some 90 per cent hydrolysis takes place at this pH in 1 hr. Under similar conditions tabun is also hydrolysed to cyanide to the extent of about 80 per cent in 12 hr. There is a concurrent diminution of toxicity as the hydrolysis proceeds. Even in distilled water 50 per cent of the cyanide is split off in 9 hr. This instability would seem to render this compound ineffective as a toxic agent for use on a large scale. 

The ester group is then hydrolysed, and the hydrolysis normally stops at the MePO(OH)2 stage. More vigorous conditions are required to rupture the Me—P bond. Thus the normal hydrolysis product of D.F.P. and of tabun, namely, phosphoric acid, will give a positive test with ammonium molybdate, whereas the product from sarin, namely, methylphosphonic acid, will not respond to this test. Vigorous reagents such as hot nitric acid and ammonium persulphate will break the C—P link and then a positive test for phosphate is obtained with ammonium molybdate. Sarin can be prepared in a variety of ways. Three... 

Irreversible cholinesterases are mostly organophosphorus compounds and combine only with esteratic site of cholinesterase and that site gets phosphorylated. The hydrolysis of phosphorylated site produces irreversible inhibition of cholinesterase. And, because, of this property, the therapeutic usefulness is very limited. Most of the compounds are used as insecticides e.g. parathion, malathion and war gases e.g. tabun, sarin, soman etc. 

H20, and multiple adduct ions using ESI. 0-Ethyl (V,(V-dimethylphosphoramidic acid, the hydrolysis product of tabun, gave an abundant MH+ plus polymeric ions (28). 

Nerve agents are hydrolyzed by the enzyme organophosphate (OP) hydrolase. The hydrolysis of GB, soman (GD), tabun (GA), and diisopropyl flu-orophosphate occurs at approximately the same rate. The isomers of the asymmetric OPs may differ in overall toxicity, rate of aging, rate of cholinesterase inhibition, and rate of detoxification. The rates of detoxification differ for different animal species and routes of administration. The onset of effects from nerve agents depends on the route, duration, and amount of exposure. The effects can occur within seconds to several minutes after exposure. There is no... 

Tabun has a stereogenic (chiral) phosphoms atom and exists as a pair of enantiomers. A gas chromatograph study of the enantiomers of tabun has been reported (Degenhardt et al., 1986). Separation was achieved through the use of bis[(l/f)-3-(heptafluorobutyryl-camphorate)nickel(II). This approach also separated stereoisomers of both sarin and soman. These authors also reported the stereospecific hydrolysis of racemic tabun using phosphorylphosphatases. They noted the species (mouse, rat, horse) dependence of the hydrolysis. Dilute solutions of tabun in inert solvents (e.g., carbon tetrachloride) exhibit optical stability for months at — 25°C. 

The reaction of sarin with hydrogen chloride has been reported and kinetics determined by NMR imaging (Bard et al., 1970). With rate constants determined at 25°C, 81.5°C, and 100°C, Arrhenius analysis led to a calculated activation energy of 17.8 kcal/mole. The base-induced hydrolysis of sarin analogs and tabun was studied by Larsson (1958b) and the half-life of GA has been estimated to be 1.5 min at pH = 11 at 25°C. Ultimately, and depending on conditions (pH, reaction times, and so forth), hydrolysis products may include fluoride ion (or hydrogen fluoride), the 1-methylethyl ester of methylphosphonic acid, methylphosphonic acid, and 2-propanol. 

Larsson, L. 1952. A spectrophotometric study in infra-red of the hydrolysis of dimethylamido-ethoxy-phos-phoryl cyanide (tabun). Acta Chemica Scandinavica, 6 1470-1476 and references cited therein see also The hydrolysis of dimethylamido-ethoxy-phosphoryl cyanide (tabun). Acta Chemica Scandinavica, 1953, 7 306-314. 

Larsson, L. 1958a. The alkaline hydrolysis of two sarin analogues and of tabun. Acta Chemica Scandinavia, 12 783-785. 

Augustinsson, K.-B. and Heimburger, G., The enzymic hydrolysis of organophosphorus compounds. 1. Occurrence of enzymes hydrolyzing tabun, Acta Chem. Scand., 8, 753, 1954. 

The reaction of tabun with nucleophiles is more complex than that of the simple phos-phorylfluoridates. The courses of such reactions are pH dependent and, according to the conditions, cleavage of either the P—N bond or the P—CN bond can predominate , as shown in Scheme 11. At low pH, in aqueous acid, protonation of the basic nitrogen atom leads to initial P—N cleavage with loss of dimethylamine, with further displacement of cyanide and ultimately the ethoxy group (under more forcing conditions). Under basic conditions, cyanide ion is displaced preferentially. At pH 7, the hydrolysis is slow and proceeds by non-selective multiple reaction pathways. 

The primary factor for the hydrolysis of nerve agents is their aqueous solubility. Sarin is more soluble than soman or tabun. 

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