Calculation Of V-S,V-Max And Its Use As A Descriptor For The Theoretical Calculation Of Pka Values For Carboxylic Acids

The theoretical calculation of pKa values for BrOnsted acids is a challenging task that involves sophisticated and time-consuming methods. Therefore, heuristic approaches are efficient and appealing methodologies to approximate these values. Herein, we used the maximum surface electrostatic potential (V-S,V-max) on the acidic hydrogen atoms of carboxylic acids to describe the H-bond interaction with water (the same descriptor that is used to characterize sigma-bonded complexes) and correlate the results with experimental pKa values to obtain a predictive model for other carboxylic acids. We benchmarked six different methods, all including an implicit solvation model (water): Five density functionals and the MOller-Plesset second order perturbation theory in combination with six different basis sets for a total of thirty-six levels of theory. The B97X-D/cc-pVDZ level of theory stood out as the best one for consistently reproducing the reported pKa values, with a predictive power of 98% correlation in a test set of ten other carboxylic acids.