Nerve gas, hydrolysis

M. Kataoka et al., Effect of pedological characteristics on aqueous soil extraction recovery and tert-butyldimethylsilylation yield for gas chromatography-mass spectrometry of nerve gas hydrolysis products from soils. Environ. Sci. Technol. 35, 1823-1829 (2001)... 

M. Kataoka, K. Tsuge and Y. Seto, Efficiency of pretreatment of aqueous samples using a macroporous strong anion-exchange resin on the determination of nerve gas hydrolysis products by gas chromatography-mass spectrometry after tert-butyldimethylsilylation, J. Chromatogr. A, 891, 295-304 (2000). 

M. Noami, M. Kataoka and Y. Seto, Improved tert-butyldimethylsilylation gas chromatographic/ mass spectrometric detection of nerve gas hydrolysis products from soils by pretreatment of aqueous alkaline extraction and strong anion-exchange solid-phase extraction, Anal. Chem., 74, 4709-4715 (2002). 

Kanamori-Kataoka, M., Seto, Y. (2008) Laboratory identification of the nerve gas hydrolysis prodncts alkyl methylphosphonic acids and methylphosphonic acid, by gas chromatography-mass spectrometry after tert-butyldimethylsUylation./oMmoZ of Health Science (Tokyo, /apan), 54(5), 513-523. 

The serine proteases act by forming and hydrolyzing an ester on a serine residue. This was initially established using the nerve gas diisopropyl fluorophosphate, which inactivates serine proteases as well as acetylcholinesterase. It is a very potent inhibitor (it essentially binds in a 1 1 stoichiometry and thus can be used to titrate the active sites) and is extremely toxic in even low amounts. Careful acid or enzymatic hydrolysis (see Section 9.3.6.) of the inactivated enzyme yielded O-phosphoserine, and the serine was identified as residue 195 in the sequence. Chy-motrypsin acts on the compound cinnamoylimidazole, producing an acyl intermediate called cinnamoyl-enzyme which hydrolyzes slowly. This fact was exploited in an active-site titration (see Section 9.2.5.). Cinnamoyl-CT features a spectrum similar to that of the model compound O-cinnamoylserine, on denaturation of the enzyme in urea the spectrum was identical to that of O-acetylserine. Serine proteases act on both esters and amides. 

Menger et al. synthesized a Ci4H29-attached copper(II) complex 3 that possessed a remarkable catalytic activity in the hydrolysis of diphenyl 4-nitrophenyl phosphate (DNP) and the nerve gas Soman (see Scheme 2) [21], When 3 was used in great excess (ca. 1.5 mM, which is more than the critical micelle concentration of 0.18 mM), the hydrolysis of DNP (0.04 mM) was more than 200 times faster than with an equivalent concentration of the nonmicellar homo-logue, the Cu2+-tetramethylethylenediamine complex 9, at 25°C and pH 6 (Scheme 4). The DNP half-life is calculated to be 17 sec with excess 1.5 mM 3 at 25°C and pH 6. The possible reasons for the rate acceleration with 3 were the enhanced electrophilicity of the micellized copper(II) ion or the acidity of the Cu2+-bound water and an intramolecular type of reaction due to the micellar formation. On the basis of the pH(6-8.3)-insensitive rates, Cu2+-OH species 3b (generated with pK3 < 6) was postulated to be an active catalytic species. In this study, the stability constants for 3 and 9 and the thermodynamic pvalue of the Cu2+-bound water for 3a —> 3b + H+ were not measured, probably because of complexity and/or instability of the metal compounds. Therefore, the question remains as to whether or not 3b is the only active species in the reaction solution. Despite the lack of a detailed reaction mechanism, 3 seems to be the best detoxifying reagent documented in the literature. 

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)... 

General Atomics U.S. Army IN, USA Bulk VX nerve gas agent hydrolysis, chemical agents, explosives, 949 kg h Commissioned 1999 (pilot plant 2000-2001)... 

A molecule of acetylcholinesterase normally hydrolyzes about 1,000 molecules of acetylcholine each seconD. After reacting with a nerve gas such as sarin, the hydrolysis rate of this enzyme would be about... 

Hoskin, F.C.G. and A.H. Rouch. 1982. Hydrolysis of nerve gas by squid type diiso-propylphosphorofluoridate hydrolyzing enzyme on agarose beads. Science 215 1255-1257. 

Acetylcholinesterase, the enzyme that catalyzes this hydrolysis, has a CH2OH group that is necessary for its catalytic activity. Diisopropyl fluorophosphate (DFP), a military nerve gas, inhibits acetylcholinesterase by reacting with the CH2OH group. 

CHOLINESTERASE REACTIVATORS Although the phosphorylated esteratic site of AChE undergoes hydrolytic regeneration at a slow or negligible rate, nucleophilic agents, such as hydroxylamine (NH OH), hydroxamic adds (RCONH-OH), and oximes (RCH=NOH), reactivate the enzyme more rapidly than does spontaneous hydrolysis. Reactivation with prahdoxime (Figure 8-1E) occurs at a million times the rate of that with hydroxylamine. Several h/s-quaternary oximes are even more potent as reactivators for insectidde and nerve gas poisoning (e.g., HI-6, used in Europe as an antidote). 

Naomi et al(2002) have reported a method of detection of hydrolysis products of nerve gas present in soil. The method involves extraction with an alkali, followed by an ion-exchange pretreatment of the aqueous soil extract and derivatization to tert-butyldi-methylsilyl derivatives. The derivatives of alkylmethylphosphonic acid and methylphos-phonic are analyzed by GC-MS. 

Of topical interest is the investigation of Vermillion and Crenshaw [146] on the analysis of nerve gas degradation products in soil samples. They investigated isopropylmethylphosphonic acid (IMPA) and methylphosphonic acid (MPA) that are formed via hydrolysis of GB (sarin) under environmental conditions (Figure 10.64). In the vicinity of former production sites and future incineration plants, these two components pose a potential environmental risk, so a simple... 

The hydrolysis of VX nerve gas on concrete has been followed by NMR spectroscopy. The P NMR signals of CysP and PhsP have been used to probe the acidity of Si02-Al203 monolayer catalysts. H-ZSM-5 was examined similarly using MesPO and Bu PO. ... 

GD is likely to undergo hydrolysis in most soils. As noted above, the rate of hydrolysis will be dependent upon temperature and pH. According to Morrill et al. (1985), evaporation is the primary mechanism for the loss of the GA and GB nerve agents from soil. Although the G agents are liquids under ordinary environmental conditions, their relatively high volatility and vapor pressure permits them to be disseminated in vapor form. Because of this volatility, GD is not expected to persist in soils. 

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... 

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