Ionizing radiation results in electron ejection from DNA bases and the formation of DNA base cation radicals. Other oxidative species such as reactive oxygen radicals may also oxidize DNA bases. Among all of the parent natural DNA bases, guanine is found to have the lowest oxidation potential and thus recognized as the prime site for oxidative stress in DNA. Free electrons produced by radiation will also add to DNA bases forming the anion radicals. The accurate determination of redox potential of DNA bases, base pairs and their substituents provides information concerning the most probable sites for DNA oxidative and reductive damage. Thus, in this context we used ωb97x density functional theory in conjunction with 6-31++G(d) basis set to calculate the redox potentials of one-electron oxidized DNA bases, base pairs and analogs. SMD and polarized continuum model (PCM) were used as solvation models for calculation of the redox potential in water and in DMF (N, N-dimethylformamide). In comparison to SMD, the PCM model is found to be more accurate in matching the experimental redox potentials. Our calculated Eo(X•+/X) redox potential values using PCM were found to be in close agreement (within ca. 0.1-0.2 V) with those measured experimentally. We also find the reduction potential (Eo vs NHE) for the aqueous electron (e-aq), to be in good agreement with the experimental value of -2.87 V, using high level Gaussian-4 theory. Supported by NIH NCI under grant no. R01CA045424.

Reduction potentials of one-electron oxidized DNA bases, base pairs, and their analogs: A DFT and electrochemical study

250th National Meeting (2015)

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