Quantum mechanical/effective fragment potential (QM/EFP) study of phosphate monoester aminolysis in aqueous solution

In this work, we investigated the P-O bond cleavage of dianionic p-nitrophenyl phosphate monoester (p-NPP), with attack of aqueous methylamine on phosphorus, by using the hybrid quantum mechanical/effective fragment potential (QM/EFP) approach. We explored the structures, energetic properties, reaction mechanism, and charge distribution along the entire reaction coordinate. Our B3LYP/6-31++G(d,p)/EFP results show that the cleavage of the P-O bond of p-NPP proceeds through a concerted mechanism with an activation energy of about 26 kcal/mol and an activation free energy at 39 degrees C of 23.6 kcal/mol, in good agreement with the experimental value of 27 kcal/mol. The reaction involves a trigonal bipyramidal (TBP) transition state with less initial bonding to the nucleophile than to the leaving group. The extent of the P-O(nitrophenolate) bond dissociation at the transition state, with methylamine as the nucleophile, is less than that with OH(-). The computed charge distribution along the reaction coordinate is consistent with a progressive charge transfer from the nitrogen atom of methylamine to the phosphate unit along the reaction coordinate. A new strategy to build the initial EFP cluster, by running a classical Monte Carlo simulation and analyzing the center-of-mass radial pair distribution function, was also used.