Calculations of pK_a’s and Redox Potentials of Nucleobases with Explicit Waters and Polarizable Continuum Solvation

The SMD implicit solvation model augmented with one and four explicit water molecules was used to calculate pK_a’s and redox potentials of N-methyl-substituted nucleic acid bases guanine, adenine, cytosine, thymine, and uracil. Calculations were carried out with the B3LYP/6-31+G­(d,p) level of theory. The same numbers of water molecules were hydrogen bonded to the neutral, protonated, and deprotonated nucleobases in their unoxidized and oxidized forms. The improvement in pK_a1 involving neutrals and cations was modest. By contrast, the improvement in pK_a2 involving neutrals and anions was quite significant, reducing the mean absolute error from 4.6 pK_a units with no waters, to 2.6 with one water and 1.7 with four waters. For the oxidation of nucleobases, adding explicit waters did little to improve E(X^•,H⁺/XH), possibly because both species in the redox couple are neutral molecules at pH 7.