Aminolysis of a Model Nerve Agent: A Computational Reaction Mechanism Study of <i>O</i>,<i>S</i>‑Dimethyl Methylphosphonothiolate

The mechanism for the aminolysis of a model nerve agent, <i>O</i>,<i>S</i>-dimethyl methylphosphonothiolate, is investigated both at density functional level using M062X method with 6-311++G­(d,p) basis set and at ab initio level using the second-order Møller–Plesset perturbation theory (MP2) with the 6-311+G­(d,p) basis set. The catalytic role of an additional NH₃ and H₂O molecule is also examined. The solvent effects of acetonitrile, ethanol, and water are taken into account employing the conductor-like screening model (COSMO) at the single-point M062X/6-311++G­(d,p) level of theory. Two possible dissociation pathways, methanethiol and methyl alcohol dissociations, along with two different neutral mechanisms, a concerted one and a stepwise route through two neutral intermediates, for each pathway are investigated. Hyperconjugation stabilization that has an effect on the stability of generated transition states are investigated by natural bond order (NBO) approach. Additionally, quantum theory of atoms in molecules analysis is performed to evaluate the bond critical (BCP) properties and to quantify strength of different types of interactions. The calculated results predict that the reaction of <i>O</i>,<i>S</i>-dimethyl methylphosphonothiolate with NH₃ gives rise to parallel P–S and P–O bond cleavages, and in each cleavage the neutral stepwise route is always favorable than the concerted one. The mechanism of NH₃ and H₂O as catalyst is nearly similar, and they facilitate the shuttle of proton to accelerate the reaction. The steps involving the H₂O-mediated proton transfer are the most suitable ones. The first steps for the stepwise process, the formation of neutral intermediate, are the rate-determining step. It is observed that in the presence of catalyst the reaction in the stepwise path possesses almost half the activation energy of the uncatalyzed one. A bond-order analysis using Wiberg bond indexes obtained by NBO calculation predicts that usually all individual steps of the reactions occur in a concerted fashion showing equal progress along different reaction coordinates