Development of a chemometric correlation technique to estimate acid–base descriptors for cationic acids in non-aqueous media Original Research Article

We propose a procedure for estimating acid–base constants in organic solvents or mixture of solvents from the corresponding pKa values in aqueous medium and from certain properties of the organic solvents that characterize them. To accomplish this, we developed and validated a chemometric correlation for the calculation of the acid–base constants of different cationic acids in a broad variety of non-aqueous solvents. The parameters chosen for building the model were as follows: the acid–base constant of the compound in aqueous medium and those corresponding to the polarity–polarizability, basicity and acidity scales of the solvent. The results of the fitting were significant (p < 0.01), with a root mean error in cross-validation of 18%, with no overfitting. The prediction of the acid–base constants for an external set of compounds had a mean absolute prediction error value of less than 0.8 pKa units.