Favorable pendant-amino metal chelation in VX nerve agent model systems

We have performed DFT computational studies [B3LYP, 6-31+G] to obtain metal ion coordination isomers of VX-Me [MeP(O)(OMe)(SCH2CH2NMe2)], a model of two of the most lethal nerve agents: VX [MeP(O)(OEt)(SCH2CH2N(iPr)2)] and Russian-VX [MeP(O)(OCH2CHMe2)(SCH2CH2N(Et)2)]. Our calculations involved geometry optimizations of the neutral VX-Me model as well as complexes with H+, Li+, Na+, K+, Be2+, Mg2+, and Ca2+ that yielded 2-8 different stable chelation modes for each ion that involved mainly mono- and bidentate binding. Importantly, our studies revealed that the [O(P),N] bidentate binding mode, long thought to be the active mode in differentiating the hydrolytic path of VX from other nerve agents, was the most stable for all ions studied here. Binding energy depended mainly on ionic size as well as charge, with binding energies ranging from 364 kcal mol(-1) for Be2+ to 33 kcal mol(-1) for K+. Furthermore, calculated NMR shifts for VX-Me correlate to experimental values of VX.