Hydrolysis of nerve agents

This material is a general precursor for nerve agents. It is also commonly found as a decomposition product/impurity and degradation product from hydrolysis of nerve agents. 

Beck, J.M., Hadad, C.M. (2008). Hydrolysis of nerve agents by model nucleophiles a computational study. Chem. Biol. Interact. May 2. (Epub ahead of print)... 

TABLE 50.3. Catalytic constants for hydrolysis of nerve agents and rate constants of esterase inhibition... 

Besides direct enzymatic hydrolysis of nerve agent substrates numerous additional proteins are present in the... 

Both hydrolysis and oxidation can be speeded up by catalysts. Wagner-Jauregg et al. (1955) and Gustafson and co-workers (1959,1962,1963) have investigated the use of copper as a catalyst for the hydrolysis of nerve agents and sulphur mustard. Iron has been studied as a catalyst of oxidative decontamination the reader is referred to Yang et al (1992) for detailed comments. 

TABLE 2. Second-order rate coefficients for the hydrolysis of nerve agents with sodium hydroxide Compound A 2(OH)(mol s ) T(°C) Ref... 

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. 

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

Besides direct enz5unatic hydrolysis of nerve agent substrates, numerous additional proteins are present in organisms that allow covalent binding to OPCs, contributing to detoxification of the poison load (Figure 56.2). Serine esterases are especially predominant targets of... 

TABLE 56.3 Catalytic Constants for Hydrolysis of Nerve Agents and Rate Constants of Esterase Inhibition... 

Properties. Some physical properties of nerve agents are given in Table 2. The G-agents, miscible in both polar and nonpolar solvents, hydrolyze slowly in water at neutral or slightly acid pH and more rapidly under strong acid or alkaline conditions. The hydrolysis products are considerably less toxic than the original agent. 

Seven papers reviewed earlier here deal with chemistry about P—S bonds,251,254-257,261,263 i.e. the peroxyhydrolysis of nerve agent (284),251 the hydrolysis of di-S-butyl phosphorothioate,254 the formation of (290),255 hydrolysis of diethyl dithiophosphate,256 the isomerization/chlorination of O, O-dialkylthiophosphate (291),257 the hydrolysis of the monothioate analogues of 5 -O-methyluridine 2 - and 3 -dimethylphosphates (293) and (294),261 and the reactivity of the ribonucleotide analogue (295).263... 

M. Kataoka et al., Effect of cation-exchange pretreatment of aqueous soil extracts on the gas chromatographic-mass spectrometric determination of nerve agent hydrolysis products after tert.-butyldimethylsilylation. J. Chromatogr. A 824, 211-221 (1998)... 

Related to the Schedule 1 family of alkyl/cyclo-alkyl alkylphosphonofluoridates, are three important classes of compounds. These are the dialkyl/dicyclo-alkyl alkylphosphonates, the alkyl/cycloalkyl alkylphosphonates and the methyl alkyl/cycloalkyl alkylphosphonates, all belonging to the Schedule 2.B.4 chemicals. Per definition, Schedule 2.B.4 represents the largest number of chemicals of CWC interest. The first class consists of known impurities of nerve agents, the second class consists of the primarily formed hydrolysis products of nerve agents, and the third class, the corresponding methyl esters-DMMP (dimethyl methylphosphonate) and DIMP (diisopropyl methylphosphonate) (see Table 1) are... 

M. Katagi, M. Tatsuno, M. Nishikawa and H. Tsuchihashi, On-line solid-phase extraction liquid chromatography-continuous flow frit fast atom bombardment mass spectrometric and tandem mass spectrometric determination of hydrolysis products of nerve agents alkyl methylphosphonic acids by p-bromophenacyl derivatization, J. Chromatogr., A, 833, 169-179 (1999). 

The metabolism of nerve agents is much simpler than that of sulfur mustard. The major pathway for elimination is via enzyme-mediated hydrolysis by esterases, plus some chemical hydrolysis, as shown in Figure 10. In the case of the methylphosphonofluoridates and V agents, the major product is an alkyl methylphosphonic acid (alkyl MPA) (16). A small fraction of the nerve agent binds... 

A number of modifications/improvements to methods for the analysis of metabolites of sulfur and nitrogen mustards, and hydrolysis products of nerve agents, have been reported in a special issue of the Journal of Analytical Toxicology, 28 (5) (2004) pp. 305-392. 

Enzymatic hydrolysis is a primary route for elimination of nerve agents. Specifically, treatment for OP intoxication includes atropine, a muscarinic receptor antagonist, an anticonvulsant such as diazepam, and a cholinesterase reactivator, an oxime. It has been found that drag-induced inhibition of ACh release and accumulation in the synaptic cleft, such as adenosine receptor antagonist early in the OP intoxication, improves the chances of survival. Some AChE reactivators, such as bispyridinum oximes, HI 6 and HLo 7 with atropine, are quite effective. 

Stereoselective enzymatic degradation of nerve agents is also a current issue in developing both novel noncorrosive decontamination systems and new therapeutics making use of recombinant mutated enzymes optimized for fast and exhaustive hydrolysis of most toxic isomers (Blum and Richardt, 2008 Furlong, 2007 Ghanem and Raushel, 2005 Li et al, 2001 Tsugawa et al, 2000). 

As outlined in the toxicity section above the toxicological mechanism of action of nerve agents is based on the chemical reactivity of the nucleophilic leaving group. Therefore, metabolism in terms of degradation by hydrolysis and binding to proteins determines bioavailability and elimination processes thus regulating toxicity. 

These selected representative examples indicate that concentration-time profiles are variable despite common underlying basic chemical reactions of hydrolysis and adduct formation. Despite improving medical treatment of nerve agent poisoning the concurrence of numerous physiological and pathophysiological parameters should be understood. Therefore, establishment of a descriptive and predictive model is of importance for the medical defense of OP compounds. 

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