Hydrolysis organophosphorus compounds

Cheng, T.-C. and DeFrank, J.J. (2000) Hydrolysis of Organophosphorus Compounds by Bacterial Prolidases, in Enzymes in Action Green Solutions for Chemical Problems (eds... 

All these observations underscore the potential for application of appropriate OPAs to the destruction of organophosphorus compounds with anticholinesterase activity (Cheng and Calomiris 1996). However, since, hydrolysis results in release of fluoride, the possibility of its subsequent incorporation into organic substrates to produce fluoroacetate and 4-fluorothreonine (Reid et al. 1995) may be worth consideration. 

The toxicity of the P-halidc anhydrides, like that of phosphoroxychloride (POCl3) and of other organophosphorus compounds discussed earlier in this section, is due to their high efficiency as irreversible inactivators of acetylcholinesterase [157]. The main target organs for the lethal effects of these chemical weapons are the brain and diaphragm. As for the detoxification of the P-halide anhydrides, it can occur by a number of biochemical mechanisms, namely chemical hydrolysis, enzymatic hydrolysis, and binding to hydrolases such as carboxylesterases, cholinesterases, and albumin [68][158][159]. 

E. Walker, Soman Hydrolysis and Detoxication by a Thermophilic Bacterial Enzyme , in Enzymes Hydrolyzing Organophosphorus Compounds , Eds. E. Reiner, W. N. Aldridge, and F. C. G. Hoskin, Ellis Horwood, Chichester, UK, 1989, p. 53-64. 

Irreversible inhibition in an organism usually results in a toxic effect. Examples of this type of inhibitor are the organophosphorus compounds that interfere with acetylcholinesterase (see Box 7.26). The organophosphorus derivative reacts with the enzyme in the normal way, but the phosphory-lated intermediate produced is resistant to normal hydrolysis and is not released from the enzyme. 

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. 

Dr. P. Jeffers at the State University of New York at Cortland is gathering information to determine the persistence of organophosphorus compounds in groundwater and the effects of various soils on the degradation and transport of these compounds. Both neutral and base hydrolysis processes will be evaluated. Transport studies in soil columns will be conducted to determine the mobility of diazinon in soils. 

The onset of symptoms depends on the particular organophosphorus compound, but is usually relatively rapid, occurring within a few minutes to a few hours, and the symptoms may last for several days. This depends on the metabolism and distribution of the particular compound and factors such as lipophilicity. Some of the organophosphorus insecticides such as malathion, for example (chap. 5, Fig. 12), are metabolized in mammals mainly by hydrolysis to polar metabolites, which are readily excreted, whereas in the insect, oxidative metabolism occurs, which produces the cholinesterase inhibitor. Metabolic differences between the target and nontarget species are exploited to maximize the selective toxicity. Consequently, malathion has a low toxicity to mammals such as the rat in which the LD50 is about 10 g kg-1. 

Plant enzymes do not catalyze the hydrolysis of organophosphorus compounds greatly, but they do catalyze their oxidation. Consequently, the oxidation products accumulate more in plants than in animals, but they appear to be generally the same as those produced by animals. 

Cohen, E.M., P.J. Christen, and E. Mobach. 1971. The Inactivation of Oximes of Sarin and Soman in Plasma from Various Species. I. The Influence of Diacetylmonoxime on the Hydrolysis of Sarin. Pp. 113-131 in Proceedings of the Koninklijke Nederlandse Akademie Van Wetenschappen, Series C, Biological and Medical Sciences, Vol. 74. J.A. Cohen Memorial issue. Amsterdam North-Holland. Davies, D.R., P. Holland, and M.J. Rumens. 1960. The relationship between the chemical structure and neurotoxicity of alkyl organophosphorus compounds. Br. J. Pharmacol. 15 271-278... 

Hoskin, F.C.G., G. Chettur, S. Mainer, and K.E. Steinmann. 1989. Soman hydrolysis and detoxification by a thermophilic bacterial enzyme. In Enzymes Hydrolyzing Organophosphorus Compounds, E. Reiner, F.C.G. Hoskin, and N.W. Aldridge, Eds. Ellis Horwood, Chichester, U.K., pp. 53-64. 

Humic substances might sequester organic phosphorus-containing molecules and render phosphate available only through enzymatic hydrolysis. If so, production and release of organophosphorus compounds by the microflora would gradually result in decreased phosphate availability. Biotic equilibrium would be established after increases in alkaline... 

The classical methods of conversion of a carboxy group into an amino group, the Curtius, Hofmann, and Schmidt reactions, have frequently been used to prepare amino-substituted organophosphorus compounds. Thus, the reaction of diethyl l-(ethoxycarbonyl)akylphosphonates with hydrazine gives the corresponding hydrazides, which, after treatment with sodium nitrite and EtOH and hydrolysis with concentrated HCl, are converted into oc-aminoalkylphosphonic acids in yields of 16-80%... 

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

There are a number of reports of impurities being detected in organophosphorus compounds which are more powerful inhibitors of plasma cholinesterase than are the parent compounds (Table 22). Many of these impurities occur as a result of hydrolysis, transmethylation (H20), or other transformation during storage. 

Organophosphorus compounds are irreversible inhibitors of acetylcholine esterase and butyrylcholine esterase (BuChe, EC 3.1.1.8) because the phosphate group is irreversibly bound by the enzyme. Therefore, organophosphorus pesticides can be detected by using the free enzyme. Since the activity of cholinesterases (ChE) in normal serum is rather large (800 UA), untreated serum pools may be employed for inhibitor determination. Gruss and Scheller (1987) have shown that the hydrolysis of butyrylthiocholine iodide can be directly indicated at a membrane-covered platinum electrode polarized to +470 mV. Twenty seconds after sample addition a steady value proportional to the enzyme activity was obtained in the differentiated current-time curve. Injection of an inhibitor decreased the rate of thiocholine formation, so that the residual activity could be evaluated after 30 s (Fig. 115). 

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