Theoretical determination of activation free energies for alkaline hydrolysis of cyclic and acyclic phosphodiesters in aqueous solution

The activation free energies for alkaline hydrolysis of cyclic and acyclic phosphodiesters in aqueous solution were investigated using the first principles electronic structure calculations. For all the phosphodiesters followed a one-step bimolecular mechanism initiated by the attack of hydroxide ion at the phosphorus atom of the ester. It was observed that the hydroxide ion-catalyzed hydrolysis involved a pentacoordinated phosphorus intermediate for all examined compounds, except paraoxon. Results show that solvent effects decreases the activation free energies for the alkaline hydrolysis of phosphodiesters.