Theoretical Calculations of pKa Values for Substituted Carboxylic Acid


Six different calculation methods have been used for studying ten derivatives of carboxylic compounds. Semi-empirical methods (AM1 and PM3), Hartree Fock (HF/STO-3G and HF/3-21G), and Density Function Theory (DFT/STO-3G and DFT/6-31G) were employed to calculate many theoretical physical parameters. The calculated data were correlated with experimental values of pKa using different regression types (enter, stepwise and simple regression). Depending on the Fisher values, (HF/STO-3G) was considered as the best method to predict the pKa data compare to the (PM3) method using enter method. While (HF/3-21G) method had higher values of Fisher compared with (PM3) using (stepwise) and (simple) methods. So, Multiple linear regression was performed to obtain the prediction values using (enter) compare with (stepwise), and the two methods are the best compared with simple regression. The acid strength was affected by the type of substituent, with electron-withdrawing substituents lowering the pKa (increase the acidity of the carboxylic acid versus electron releasing groups increasing it (decreasing the acidity of the carboxylic acid).