Prediction of accurate pKa values of some α-substituted carboxylicacids with low cost of computational methods

The acidity constants (pKa) of thirty four (34) α-substituted carboxylic acids in aqueous solution have been calculated using conductor-like polarizable continuum (C-PCM) solvation model. The gasphase energies at the Density Functional Theory (DFT-MPW1PW91) and solvation energies at HartreeFock (HF) are combined to estimate the pKa values which are very close to the experimental values where, and the root-mean-square error (rmse) is less than 0.9. In addition, the pKa values predicted by Multilinear Regression (MLR), Principle Components Regression (PCR) and Partial Least Square Regression (PLSR) methods showed an excellent correlation to the experimental values where the root-mean-square error (rmse) decreases from 0.9 to 0.293, 0.326 and 0.319 respectively. Furthermore, the rmse of pKa values found less than 0.3 when the solvation models of some powerful electron withdrawing substituted acids are employed at the level of MPW1PW91 theory. The computation by different regression methods showed reasonably a better calculation of pKa values through the lower root-mean-square errors (rmse).