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. ► The gradient and intercept of the linear fitting lead to the scaling factor for the activity coefficient and the Gibbs energy of the proton in aqueous solution, respectively. ► The error between the experimental and fitted pKa values is no more than 0.2 pKa units. ► We applied this method to predict unknown pKa values of several 5-substitued uracils.