Estimation of Phosphate Ester Hydrolysis Rate Constants. II. Acid and General Base Catalyzed Hydrolysis

Abstract

AbstractSPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate acid and neutral hydrolysis rate constants of phosphate esters in water. The rate is calculated from the energy difference between the initial and transition states of the reactant molecule. This difference is a function of the reference rate and internal and external perturbations to the reference rate. The internal perturbations are comprised of electrostatic and resonance effects. The external perturbations quantify solute‐solvent interactions based on the dielectric constant of the solvent and the steric size of substituent groups. The neutral hydrolysis model has been tested against 89 observed hydrolysis rate constants at multiple temperatures. The RMS deviation of the calculated versus observed values was 1.08 log M−1 s−1. The acid hydrolysis model has been tested on 83 rate constants over a variety of temperatures. The RMS deviation of the acid hydrolysis model was 0.41 log M−1 s−1.