Quantum-Chemical Insights into Mechanisms of the Nonenzymatic Hydrolysis of Phosphate Monoesters

Abstract

The interpretation of a large number of experiments that are generally considered to support the dissociative or metaphosphate mechanism of phosphate monoesters in aqueous solution is scrutinized using results of ab initio quantum chemical calculations. It is concluded that while it is currently not clear whether the associative or dissociative mechanism of phosphate monoester hydrolysis is operating in aqueous solution, the associative transition state can be better stabilized by the interaction between the equatorial oxygens and the proton donor groups in the enzyme active sites.

Keywords::

• dimethyl phosphate
• rate constant
• activation barrier
• ab initio calculations