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 p<i>K</i>_a 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 of ∼2 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 p<i>K</i>_a data to experimentally measured p<i>K</i>_a values. After solvent cavity scaling, the MAEs for computed p<i>K</i>_a's compared to experimental results are 0.7 for B3LYP and 0.9 for CBS-QB3. In acetonitrile, the computed <i>E°</i>(XH^+•/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 <i>E</i>₇(X^•,H⁺/XH). Replacing the methyl substituent with ribose changes the calculated <i>E</i>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