Theoretical Modeling on the Reaction Mechanism of p-Nitrophenylmethylphosphate Alkaline Hydrolysis and its Kinetic Isotope Effects

Abstract

We have studied the alkaline hydrolysis of p-nitrophenylmethylphosphate (p-NPmP) in aqueous solution by means of polarizable continuum models and by hybrid quantum-mechanical/molecular-mechanical (QM/MM) methods. The theoretical predictions of kinetic isotope effects (KIEs) are in very good agreement with the experimental data, confirming a concerted asynchronous molecular mechanism. In addition, comparison of high level DFT theory with semiempirical AM1/d Hamiltonian has allowed checking the reliability of the later to be used in modeling very large molecular models containing phosphorus atoms.