Calculations of pKa values of carboxylic acids in aqueous solution using density functional theory

With the specific aim of calculating the acidity equilibrium constant (Ka) of carboxylic acids in aqueous solution we investigated the solute–solvent interactions of these acids and their corresponding anions. The pKa (−lg Ka) values have been calculated using density functional theory (DFT). The polarized continuum model (PCM) is used to describe the solvent. Using these methods, we successfully predicted the pKas of 66 carboxylic acids in aqueous with the average error of 0.5 in pKa units. Two different thermodynamic cycles have been studied. The theoretical values are in better agreement with the experimental results for those acids with moderate strength of acidity with the pKa value higher than 3.