Estimating the acidity of singly and multiply substituted benzoic acids via electrostatic potential at the nucleus

We established two good linear relationships between pKa and acidic atom’s electrostatic potential (MEP) in the gas phase by DFT methods at B3LYP/6-31+G(d, p) level of theory. We studied 13 experimentally well-characterized singly substituted benzoic acids to determine the best level of theory. A good linear relationship between MEP and the experimental pKa data has been revealed (standard deviation (STD) = 0.081, R2 = 0.937 for model 1; STD = 0.081, R2 = 0.934 for model 2), better than the computational results in the literatures. Our models also showed that it is reliable to estimate the pKa values of multiply substituted benzoic acids.