Effect of sulfur substitution for methanolysis of paraoxon: CO vs. PO bond cleavage from density-functional theory

Density functional theory calculations have been used to explore the intrinsic reactivity for the methanolysis of paraoxon (native) and the analogous reactions with sulfur substitutions at key oxygen positions (bridging O2′, O2″, O5′ and nonbridging OP) in the gas phase and in solution. P-path involving the nucleophilic attack at the phosphorus atom and C-path involving the attack at the beta carbon atom are taken into account for the series of reactions. The reactions proceed through the SN2-type mechanism for both of the two pathways. It is found that except for the reaction of sulfur substitution at O5′ position the P-path is more favorable than the C-path kinetically. The products of the C-path are more accessible than the P-path thermodynamically, except for the reaction of sulfur substitution at the leaving (O2′ or O2″) position. The bond-forming is more advanced than the bond-breaking for all of the P-paths, while the bond-breaking is more advanced for all of the C-paths. The calculations provide a comprehensive data set, which are consistent with the previous experimental and theoretical studies and allow interpretation of measured thio effects.