Estimation of empirically fitted parameters for calculating p K a values of thiols in a fast and reliable way

Two empirically fitted parameters (m and C 0) for the calculation of pK a values for thiols are provided for the first time, at 74 levels of theory. The coefficients were obtained by least-squares fits of the difference in Gibbs energy between each acid and its conjugated base versus experimental pK a values. The reliability of this fitted parameters approach (FPA) was confirmed using an independent test set of molecules. It was found that deviations from experiments are systematically lower than 0.5 pK a units, in terms of mean unsigned errors. In addition, all the tested levels of theory produced maximum absolute errors lower than 1 pK a unit. The parameters estimated here are expected to facilitate pK a calculations, using electronic structure-based strategies, with uncertainties close to the experimental ones. Albeit the present study deals only with molecules of modest complexity, i.e., the reliability of the FPA for more complex systems remains to be tested, it seems to be a promising approach for obtaining pK a values of thiols in a fast and reliable way.