Potential energy surfaces for the phosphonylation of sarin and acetylcholinesterase (AChE) have been
theoretically studied at the B3LYP/6-311G(d,p) level of theory. The obtained results show that the
phosphonylation process involves a two-step addition-elimination mechanism, with the first step (addition
process) being the rate-determining step, while by comparison, the ensuing steps are very rapid. Stable trigonal
bipyramidal intermediates are formed in the studied pathways. It is also revealed that the catalytic triad of
acetylcholinesterase plays the catalytic role in the reaction by speeding up the phosphonylation process, as it
does in the acylation reaction of ACh and AChE. The effect of aqueous solvation was accounted for via the
polarizable continuum model. It is concluded that the enzymatic reaction here is influenced strongly by the
solvent environment.