A Simple scheme for estimating the pKa values of 5-substituted uracils

We have introduced a new computational method to provide an acid dissociation constant (pKa) value of an imino-proton in 5-substituted uracil. A linear fitting is applied to the experimentally observed pKa to compute the Gibbs energy difference of a deprotonation reaction by a conductor-like polarizable continuum model (CPCM)-B3LYP/aug-cc-pVDZ level of theory. Despite its simplicity in our method for evaluating pKa, the error falls within 0.5 pKa units except for X = O− (X: ligand of C5). The predicted pKa values for other 5-substituted uracils are also found to agree well with experimental data.