Phosphorothioates, hydrolysis

The rat LD qS are 13, 3.6 (oral) and 21, 6.8 (dermal) mg/kg. Parathion is resistant to aqueous hydrolysis, but is hydroly2ed by alkah to form the noninsecticidal diethjlphosphorothioic acid and -nitrophenol. The time required for 50% hydrolysis is 120 d ia a saturated aqueous solution, or 8 h ia a solution of lime water. At temperatures above 130°C, parathion slowly isomerizes to 0,%diethyl 0-(4-nitrophenyl) phosphorothioate [597-88-6] which is much less stable and less effective as an insecticide. Parathion is readily reduced, eg, by bacillus subtilis ia polluted water and ia the mammalian mmen to nontoxic 0,0-diethyl 0-(4-aminophenyl) phosphorothioate, and is oxidized with difficulty to the highly toxic paraoxon [511-45-5] diethyl 4-nitrophenyl phosphate d 1.268, soluble ia water to 2.4 mg/L), rat oral LD q 1.2 mg/kg. 

Plapp FW, Casida JE. 1958. Hydrolysis of the alkyl-phosphate bond in certain dialkyl aryl phosphorothioate insecticides by rats, cockroaches, and alkali. J Econ Entomol 51 800-803. 

Finally, non-racemic phosphorothioic and phosphonothioic acids 98 were obtained via a PTE-catalysed stereoselective hydrolysis of the prochiral substrates 97 (Equation 48). ° The absolute configurations of the thioacids 98 depended on whether native PTE or its mutants were used. 

The first step in the degradation of phosphate and phosphorothioate esters is hydrolysis, and substantial effort has been directed to all groups. Investigations have also been directed to the use of their degradation products as a source of phosphate for the growth of bacteria, and a wide range of phosphates, dialkylphosphates, and phosphorothioates has therefore been examined as sources of phosphorus (Cook et al. 1978). 

It is important to emphasize that the initial metabolites after hydrolysis may be both toxic and sometimes resistant to further degradation. Examples include nitrophenols, whose degradation is discussed in Chapter 9, Part 5 and 3,5,6-trichloropyridin-2-ol (Feng et al. 1997), which is produced by the hydrolysis of chlorpyrifos (0,0-diethyl-0-[3,5,6-trichlo-2-pyridyl]phosphorothioate). 

Fig. 9.12. Mechanism of monooxygenase-catalyzed oxidative desulfuration and dephosphorylation of phosphorothioates (9.67, X = O) and phosphorodithioates (9.67, X = S). The first step is believed to be an 5-oxygenation followed by rearrangement with sulfur expulsion (oxidative desulfuration) or hydrolysis to form phosphate and phosphorothioic 0,0-acid diesters.

F. Hollfelder, D. Herschlag, The Nature of the Transition State for Enzyme-Catalyzed Phosphoryl Transfer. Hydrolysis of O-Aryl Phosphorothioates by Alkaline Phosphatase , Biochemistry 1995, 34, 12255-12264. 

Mechanistic studies of the acid hydrolysis of S -butyl phosphorothioate (286) have been reported. 

The hydrolysis half-life in three different natural waters was approximately 48 d at 25 °C (Macalady and Wolfe, 1985). At 25 °C, the hydrolysis half-lives were 120 d at pH 6.1 and 53 d at pH 7.4. At pH 7.4 and 37.5 °C, the hydrolysis half-life was 13 d (Freed et al, 1979). At 25 °C and a pH range of 1-7, the hydrolysis half-life was about 78 d (Macalady and Wolfe, 1983). However, the alkaline hydrolysis rate of chlorpyrifos in the sediment-sorbed phase were found to be considerably slower (Macalady and Wolfe, 1985). In the pH range of 9-13, 3,5,6-trichloro-2-pyridinol and 0,0-diethyl phosphorothioic acid formed as major hydrolysis products (Macalady and Wolfe, 1983). The hydrolysis half-lives of chlorpyrifos in a sterile 1% ethanoFwater solution at 25 °C and pH values of 4.5, 5.0, 6.0, 7.0, and 8.0 were 11, 11, 7.0, 4.2, and 2.7 wk, respectively (Chapman and Cole, 1982). 

Chlorpyrifos is stable to hydrolysis in the pH range of 5-6 (Mortland and Raman, 1967). However, in the presence of a Cu(lf) salt (i.e., cupric chloride) or when present as the exchangeable Cu(II) cation in montmorillonite clays, chlorpyrifos is completely hydrolyzed via first-order kinetics in <24 h at 20 °C. It was suggested that chlorpyrifos decomposition in the presence of Cu(II) was a result of coordination of molecules to the copper atom with subsequent cleavage of the side chain containing the phosphorus atom forming 3,5,6-trichloro-2-pyridinol and 0,0-ethyl-0-phosphorothioate (Mortland and Raman, 1967). 

Plant Diaziuou was rapidly absorbed by and translocated in rice plants. Metabolites identified in both rice plants and a paddy soil were 2-isopropyl-4-methyl-6-hydroxypyrimidine (hydrolysis product), 2-(l -hydroxy-l -methyl)ethyl-4-methyl-6-hydroxypyrimidine, and other polar compounds (Laanio et al, 1972). Oxidizes in plants to diazoxon (Laanio et al., 1972 Ralls et al, 1966 Wolfe et al., 1976) although 2-isopropyl-4-methylpyrimidin-6-ol was identified in bean plants (Kansouh and Hopkins, 1968) and as a hydrolysis product in soil (Somasundaram et al., 1991) and water (Suffet et al., 1967). Five d after spraying, pyrimidine ring-labeled C-diazinon was oxidized to oxodiazinon which then hydrolyzed to 2-isopropyl-4-methylpyrimidin-6-ol which, in turn, was further metabolized to carbon dioxide (Ralls et al, 1966). Diazinon was transformed in field-sprayed kale plants to hydroxydiazinon 0,0-diethyl-0-[2-(2 -hydroxy-2 -propyl)-4-methyl-6-pyrimidinyl] phosphorothioate which was not previously reported (Pardue et al., 1970). 

Based on pseudo-first-order kinetics of phorate hydrolysis, the following half-lives were reported 52 h at pH 5.7, 61 h at pH 8.5, 62 h at pH 9.4, and 33 h at pH 10.25. The major hydrolysis product is ethanethiol which quickly oxidizes to diethyl disulfide. In addition, diethyl dithiophosphate and diethyl phosphorothioate are potential products of phorate hydrolysis (Hong and Pehkonen, 1998). 

Parathion (0,0-diethyl 0-/7-nitrophenyl phosphorothioate) is degraded in the near subsurfaee aerobie environment via hydrolysis, where two degradation products are observed, diethylthiophosphoric acid and p-nitrophenol, according to the schematic pathway described in Fig. 16.35. Abiotic hydrolysis of parathion in the subsurface is a result of a surface-mediated transformation (see Sect. 16.1) or a biodegradation process. 

Chlorpyrifos, 0-0-diethyl 0-(3,5,6-trichloro-2-pyridyl) phosphorothioate, is the compound for which the most exhaustive kinetic investigations were conducted (10). The kinetics of the hydrolysis as a function of pH in distilled and buffered distilled water systems is summarized by the pH-rate profile shown in Figure 2 (7j. The value, k jg=(6.22 0.09) x 10 min is the neutral hydrolysis rate constant for chlorpyrifos in distilled water at 25°C. 

Diazinon and Ronnel. The conclusion that neutral hydrolysis of sorbed chlorpyrifos is characterized by a first-order rate constant similar to the aqueous phase value is strengthened and made more general by the results for diazinon, 0,0-diethyl 0-(2-iso-propyl-4-methyl-6-pyrimidyl) phosphorothioate, and Ronnel, 0,0-dimethyl 0-(2,4,5-trichlorophenyl) phosphorothioate (10). The results for the pH independent hydrolysis at 35°C for these compounds in an EPA-26 sediment/water system (p=0.040) are summarized in Table IV. Because the aqueous (distilled) values of k for diazinon and Ronnel are similar in magnitude to the value for chlorpyrifos, and because these values were shown by the chlorpyrifos study to be slow compared to sorption/desorption kinetics, computer calculations of were not deemed necessary and were not made for these data. 

Goethite (surface are 50 m g" ) has been reported to catalyse the hydrolysis of carboxylate and phosphorothioate esters (Torrents and Stone, 1994). The authors suggest that the sulphur of the thioester binds to the surface Fe of the goethite and thereby reduces the electron density at the P atom which in turn facilitates the nucleophilic attack by OH and promotes hydrolysis. 

Torrents, A. Stone, A.T (1994) Oxide surface-catalysed hydrolysis of carboxylate esters and phosphorothioate esters. Soil Sd. Soc. Am. J. 58 738-745... 

Stereochemical studies support in-line mechanisms for both the transesterification and hydrolysis steps of ribonuclease catalysis. For example, chiral uridine 2, 3 -cyclic phosphorothioates are hydrolyzed with inversion of configuration, with the diastereoisomer shown yielding a 2 -monophosphothioate of the R configuration at phosphorus. 

A distinctive feature of the alkaline phosphatase-catalyzed hydrolysis is that the relative rates of hydrolysis of the many different phosphate and S-phosphorothioate esters are nearly the same (it is difficult to get precise rate values because of product inhibition by phosphate, the Km... 

In contrast to the above, Neumann 109), using an enzyme solution (pH 8.7, 0.1 M tris, 25°C) 3000 times more concentrated than that of Breslow and Katz, did not detect hydrolysis of O-p-nitrophenyl phosphorothioate after 2 hr. She also reported the isolation of an extremely stable enzyme-nitrophenyl phosphorothioate complex. One might speculate that in the light of the extreme stability of the proposed enzyme-phosphorothioate complex, the complex may actually be a covalent species... 

Hydrolysis Products of Various 0- and S-Substituted Monoesters of Phosphorothioic Acid by Alkaline and Acid Phosphatases ... 

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