Preferred dissociative mechanism of phosphate monoester hydrolysis in low dielectric environments

Phosphate monoester hydrolysis is studied theoretically with particular focus on solvent effects on the reaction mechanism. Free energy profiles for methyl monophosphate and triphosphate anions are calculated at the DFT/COSMO level by determining the reaction path with a chain-of-replicas method. The result suggests that in low dielectric environments, the stepwise mechanism involving prior metaphosphate dissociation is preferred over concerted one that involves a penta-coordinated transition state. It is discussed that the above preference for stepwise mechanism may be relevant for a dramatic increase in phosphate hydrolysis rate observed in low dielectric media.