Easy to Use DFT Approach for Computational pKa Determination of Carboxylic Acids

In pKa computational determination, the challenge in exploring and fostering new methodologies and approaches goes in parallel with the amelioration of computational performances. In this paper a "ready to use methodology" has been compared to other strategies, such as the re-shaping in solvation cavity (Bondi radius re-shaping), wanting to assess its reliability in predicting the pKa of a broad list of carboxylic acids. Thus, the functionals B3LYP and CAM-B3LYP have been selected, using SMD as continuum solvation model. Exploiting our previous results, two water molecules were made explicit on the reaction centre. Data show that our model (CAM-B3LYP/2H