Theoretical calculation of the pKa values of some drugs in aqueous solution

Abstract In this work, calculations of p K a values have been performed on benzoic acid and its para‐substituted derivatives and some drugs by using Gaussian 98 software package. Gas‐phase energies were calculated with HF/6‐31 G** and B3LYP/6‐31 G** levels of theory. Free energies of solvation have been computed using the polarizable continuum model (PCM), conductor‐like PCM (CPCM), and the integral equation formalism‐PCM at the same levels which have been used for geometry determination in the gas‐phase. The results that show the calculated p K a values using the B3LYP are better than those using the corresponding HF. In comparison to the other models, the results obtained indicate that the PCM model is a suitable solvation model for calculating p K a values. For the investigated compounds, a good agreement between the experimental and the calculated p K a values was also observed. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011