Estimation of pKa for organic oxyacids using calculated atomic charges

A method for the estimation of pKa from empirically calculated atomic charges has been developed and tested on a diverse set of organic oxyacids. The approach involves a comparison of the atomic charges calculated for both the acid and the negative ion that is formed after loss of the acidic proton. These charges have been used in conjunction with the familiar concepts of induction and resonance to develop an accurate formula to predict pKa. Results for a set of 135 compounds, including alcohols, phenols, and carboxylic acids, yielded a fit of pKa with r = 0.993 and an rms error of 0.455. © John Wiley & Sons, Inc.