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

have introduced a new computational method to provide an acid dissociation constant (pK(a)) value of an imino-proton in 5-substituted uracil. A linear fitting is applied to the experimentally observed pK(a) 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 pK(a), the error falls within 0.5 pK(a) units except for X = O (X: ligand of C5). The predicted pK(a) values for other 5-substituted uracils are also found to agree well with experimental data. (C) 2010 Elsevier B.V. All rights reserved.