In this theoretical investigation using density functional theory, the addition of the electron-donating methyl group in cytosine at carbon 5 of the ds-C−G pair does not affect the ionization potential threshold energy of guanine because of extensive intramolecular bonding.

Abstract

Gas-phase and aqueous vertical ionization potentials, vIP_gas and vIP_aq respectively and measurements of the molecular electrostatic and local ionization maps calculated at the DFT/B3LYP-D3/ 6–311+G** level of theory and the C-PCM reaction field model for single- and double-stranded CpG and 5MeCpG pairs show that the vIP_aq for single- and double-stranded pairs of C−G and 5MeC−G are practically the same, in the range of 5.79 to 5.81 eV. The aqueous adiabatic ionization potentials for single-stranded CpG and 5MeCpG are 5.52 eV and 5.51 eV respectively and they reflect the nuclear reorganization that takes place after the abstraction of the electron. The aqueous adiabatic ionization energy values that correspond to the CpG^+. radical cation and the hydrated electron, e^−,, being at infinite distance, adIP_aq+V_o, are 3.92 eV and 3.91 eV respectively with (V_o=−1.6 eV) Analysis of data suggest that the HOMO-LUMO energy gap in the hard/soft-acid/base (HSAB) concept cannot be used a priori to determine the effect of cytosine methylation on the guanine enhanced oxidative damage in DNA.