Oximes (especially oximate anions) are used as potential reactivators of OP-inhibited AChE due to their
unique R-effect nucleophilic reactivity. In the present study, by applying the DFT approach at the B3LYP/
6-311G(d,p) level and the Møller-Plesset perturbation theory at the MP2/6-311G(d,p) level, the formoximateinduced
reactivation patterns of the sarin-AChE adduct and the corresponding reaction mechanism have been
investigated. The potential energy surface along the pathway of the reactivation reaction of sarin-inhibited
AChE by oxime reveals that the reaction can occur quickly due to the relatively low energy barriers. A
two-step process is a major pathway proposed for the studied reactivation reaction. Through the nucleophilic
attack, the oximate first binds to the sarin-AChE adduct to form a relatively stable phosphorus complex. The
regeneration of the serine takes place subsequently through an elimination step, which is expected to be
competitive with the nucleophilic attacking process. The polarizable continuum model (PCM) has been applied
to evaluate the solvate effects on the pathway. It is concluded that the reaction energy barriers are also low
enough for the reaction to easily occur in solvent. The results derived from both the gas-phase model and the
aqueous solvation model suggest that the studied oximate anion is an efficient antidote reagent for sarininhibited
AChE.