Vertical Ionization Energies and Electron Affinities of Native and Damaged DNA Bases, Nucleotides, and Pairs from Density Functional Theory Calculations: Model Assessment and Implications for DNA Damage Recognition and Repair.

To assess the effect of an 8-oxoguanine (8OG) defect base on the vertical ionization energies (VIEs) and electron affinities (VEAs) of DNA, density functional theory calculations were carried out for native and defect DNA bases and nucleotides, as well as for larger fragments containing one or multiple pairs. Absolute values of VIE and VEA under implicit solvation did not converge as a function of model size even up to the largest systems taken into consideration (3 base pairs/2 nucleotide pairs). Nonetheless, a consistent trend was observed for the relative difference in the VIE of native and damaged DNA showing that the defect was lowering the VIE by -0.1 eV for the largest fragments. This strongly suggests that the presence of 8OG makes the DNA more easily oxidizable and is in line with experimental evidence that a defect region can act as a sink of oxidative damage. In contrast, relative differences in VEA were very small and varied inconsistently around 0.01 eV. This seems to indicate that insertion of 8OG has a negligible effect on the electron capturing properties of DNA. Similar conclusions can be drawn by the adiabatic IEs and EAs computed for some of the larger fragments. Analysis of the hole and excess electron distributions was consistent with the above trends. The findings presented here support the possibility that a mechanism based on hole transport through DNA may be efficiently employed by the cell for the detection of defect bases.