Theoretical Determination of One-Electron Oxidation Potentials for Nucleic Acid Bases

The oxidation potentials for N-methyl substituted nucleic acid bases guanine, adenine, cytosine, thymine, uracil, xanthine, and 8-oxoguanine were computed using B3LYP and CBS-QB3 with the SMD solvation model. Acid-base and tautomeric equilibria present in aqueous solution were accounted for by combining standard redox potentials with calculated plc and tautomerization energies to produce an ensemble averaged pH dependent potential. Gas phase free energies were computed using B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d,p) and CBS-QB3. Solvation free energies were computed at the SMD/B3LYP/6-31+G(d,p) level of theory. Compared to experimental results, calculations with the CBS-QB3 level of theory have a mean absolute error (MAE) of ca. 1 kcal/mol for the gas phase proton affinity/gas phase basicity and an MAE of ca. 0.04 eV for the adiabatic/vertical ionization potentials. The B3LYP calculations have a MAE similar to 2 of kcal/mol for the proton affinity/gas phase basicity data but systematically underestimated ionization potentials by 0.14-0.21 eV. Solvent cavities for charged solute species were rescaled uniformly by fitting computed pK(a) data to experimentally measured pK(a), values. After solvent cavity scaling, the MAEs for computed pK(a)'s compared to experimental results are 0.7 for B3LYP and 0.9 for CBS-QB3. In acetonitrile, the computed E degrees(XH+center dot/XH) redox potentials are systematically lower than experimentally measured potentials by 0.21 V for CBS-QB3 and 0.33 V for B3LYP. However, the redox potentials relative to adenine are in very good agreement with experimental results, with MAEs of 0.10 V for CBS-QB3 and 0.07 V for B3LYP. In aqueous solution, B3LYP and CBS-QB3 have MAEs of 0.21 and 0.19 V for E-7(X-center dot,H+/XH). Replacing the methyl substituent with ribose changes the calculated E-7 potentials by 0.1-0.2 V. The calculated difference between the guanine and adenine oxidation potentials is too large compared to experimental results, but the calculated difference between guanine and 8-oxoguanine is in good agreement with the measured values.