Disulfoton hydrolysis

Disulfoton causes neurological effects in humans and animals. The mechanism of action on the nervous system depends on the metabolism of disulfoton to active metabolites. The liver is the major site of metabolic oxidation of disulfoton to disulfoton sulfoxide, disulfoton sulfone, demeton S-sulfoxide and demeton S-sulfone, which inhibit acetylcholinesterase in nervous tissue. These four active metabolites are more potent inhibitors of acetylcholinesterase than disulfoton. Cytochrome P-450 monooxygenase and flavin adenine dinucleotide monooxygenase are involved in this metabolic activation. The active metabolites ultimately undergo nonenzymatic and/or enzymatic hydrolysis to more polar metabolites that are not toxic and are excreted in the urine. 

Three different pathways are associated with the metabolism of disulfoton (I) oxidation of the thioether sulfur to produce sulfoxides and sulfones (2) oxidation of the thiono sulfur to produce the oxygen analogs and (3) hydrolysis of the P-S-C linkage to produce the corresponding phosphorothionate or phosphate (WHO 1976) (see Figure 2-3). These pathways have been elucidated from data obtained in humans exposed to disulfoton and from in vivo and in vitro metabolism studies in rats and mice. 

The three processes responsible for the transformation and degradation of disulfoton in water are abiotic hydrolysis, photosensitized oxidation, and biodegradation. Disulfoton is most stable towards... 

After a fire in a chemical storehouse at Schweizerhalle, Switzerland, in November 1986, several tons of various pesticides, solvents, dyes, and other raw and intermediate chemicals were flushed into the Rhine River (Capel et al., 1988 Wanner et al., 1989). Among these chemicals was the insecticide disulfoton, of which 3500 kg were introduced into the river water (11°C, pH 7.5). During the 8 days travel time from Schweizerhalle to the Dutch border, 2500 kg of this compound were eliminated from the river water. Somebody wants to know how much of this elimination was due to abiotic hydrolysis. Since in the literature you do not find any good kinetic data for the hydrolysis of disulfoton, you make your own measurements in the laboratory. Under all selected experimental conditions, you observe (pseudo)first-order kinetics, and you get the results given below. 

With deeper understanding of the rate laws applicable to these hydrolases, now we need to deduce the parameters that combine to give corresponding khl0 values for Michaelis-Menten cases (Eq. 17-80). We may now see that the mathematical form we used earlier to describe the biodegradation of benzo[f]quinoline (Eq. 17-82) could apply in certain cases. Further we can rationalize the expressions used by others to model the hydrolysis of other pollutants when rates are normalized to cell numbers (e.g., Paris et al., 1981, for the butoxyethylester of 2,4-dichlorophenoxy acetic acid) or they are found to fall between zero and first order in substrate concentration (Wanner et al., 1989, for disulfoton and thiometon). 

Disulfoton is relatively stable in water at neutral and acidic pH. It is resistant to hydrolysis with a half-life of 323 days at pH 7. Alkalinity enhances hydrolysis. Disulfoton has been shown to persist for 1 week in sandy loam soil. 

Let us now turn to an example of nucleophilic substitution involving a group of pollutants other than alkyl halides. We consider the hydrolysis of thiometon and disulfoton, two insecticides that were among the major contaminants that entered the Rhine River after the famous accident at Schweizerhalle in Switzerland in 1986 (Capel et al., 1988). This example is representative for the hydrolysis of a variety of phosphoric and thiophosphoric acid derivatives (e.g., esters, thioesters, see Fig. 1), and it illustrates that hydrolysis of a more complex molecule may be somewhat more complicated. The kinetic data, as well as the proposed mechanisms of hydrolysis of thiometon and disulfoton, are presented in Table 4 and Figure 2, respectively. In these cases, the base catalyzed reaction... 

TABLE 4. Kinetic Data for the Abiotic Hydrolysis of Disulfoton and Thiometon... 

Figure 2. Possible hydrolysis mechanisms for disulfoton (R = CH3) and thiometon (R = H). I Nucleophilic displacement SN2) at the ethyl or methyl group (C-O cleavage). II Nucleophilic displacement (SN2) at the phosphorus atom (P-S cleavage). Ill Nucleophilic displacement (SN2, Ilia SNi, IHb) at the 2-(ethylthio)-ethyl group (C-S cleavage). For details, see Wanner et al. (1989).

It is considerably more sensitive to hydrolysis than disulfoton, as a result of the mercaptal structure. Its metabolism in plants is identical with that of disulfoton and, sulfoxide and sulfone derivatives, more readily soluble in water, are formed. 

Intramolecular nucleophilic substitution reactions also are thought to compete with hydrolysis (i.e., 8 2 reaction with H2O) in the hydrolysis of several or-ganophosphorus esters. For example, the C-S cleavage of thiometen (R = H) and disulfoton (R = CH3) can occur by intramolecular nucleophilic substitution by the sulfur atom of the electron-withdrawing group, which results in the formation of the cyclic sulfonium ion which subsequently reacts with water to give 2-(ethylthio)ethanol (Wanner et al., 1989). 

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