Computational methods modeled the hydrolysis of the organophosphate O, S-diethylphenyl phosphonothioate (DEPP) by the monomeric MoO42- molybdate. This was the first case of phosphonothioate hydrolysis by a high oxidation state group VI complex that proceeded with turnover under mild conditions (pH 7, 30 oC). DEPP serves as an analog of organophosphate neurotoxins that include agricultural pesticides and chemical warfare agents. Hydrolysis by MoO42- yields ethylphenyl phosphonate resulting from exclusive P – S scission which is the preferred bond cleavage for remediation of a toxic phosphonothioate. The mechanism for this hydrolysis was modeled with density functional theory methods for three possible hydrolytic routes. Two pathways wherein the Mo(VI) center serves as a Lewis acid to activate the phosphorus center are proposed. Alternatively, the oxoanion of MoO42- could attack the phosphorus center of DEPP in a SN2(P) fashion to form a mixed molybdate-phosphonate anhydride intermediate; this is followed by rapid hydrolysis. DFT calculations (B3LYP, TPSSh, TPSS and BP86) at the G++(d,p) level indicate this nucleophilic route is a viable pathway for the catalytic hydrolysis of DEPP by MoO42-. The initial SN2(P) nucleophilic attack was successfully modeled that included a transition state search. This was followed by hydroxide attack on the molybdate-phosphonate intermediate that was located as a local minima.

Computational investigation of phosphonothioate-neurotoxin hydrolysis by monomeric MoO42-

253rd National Meeting (2017)

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