The Substrate-Assisted General Base Catalysis Model for Phosphate Monoester Hydrolysis: Evaluation Using Reactivity Comparisons

Abstract

Reactions of phosphate monoesters are ubiquitous in biological chemistry. Hence, this class of reactions has been subjected to extensive mechanistic analysis by physical organic chemists seeking to understand the nonenzymatic reactions and to apply this understanding to the corresponding enzymatic reactions. Substrate-assisted general base catalysis of phosphoryl transfer, in which a proton from the nucleophile is transferred to a nonbridging phosphoryl oxygen of the substrate prior to attack, has recently been proposed as a mechanism for both nonenzymatic and enzymatic reactions of phosphate monoester dianions and related compounds, in opposition to the previously accepted mechanism of direct nucleophilic reaction. We have evaluated this new mechanism for the hydrolysis of a phosphate monoester dianion in solution by considering the reactivity of the monoester monoanion that is a reaction intermediate in the proposed proton transfer. The monoanion of the monoester 2,4-dinitrophenyl phosphate (DNPP-) and ...