Valence Anion of Thymine in the DNA π-Stack

Abstract

Most of theoretical data on the stability of radical anions supported by nucleic acid bases have been obtained for anions of isolated nucleobases, their nucleosides, or nucleotides. This approach ignores the hallmark forces of DNA, namely, hydrogen bonding and pi-stacking interactions. Since these interactions might be crucial for the electron affinities of nucleobases bound in DNA, we report for the first time on the stability of the thymine valence anion in trimers of complementary bases possessing the regular B-DNA geometry but differing in base sequence. In order to estimate the energetics of electron attachment to a trimer, we developed a thermodynamic cycle employing all possible two-body interaction energies in the neutral and anionic duplex as well as the adiabatic electron affinity of isolated thymine. All calculations were carried out at the MP2 level of theory with the aug-cc-pVDZ basis set. The two-body interaction energies were corrected for the basis set superposition error, and in benchmark systems, they were extrapolated to the basis set limit and supplemented with correction for higher order correlation terms calculated at the CCSD(T) level. We have demonstrated that the sequence of nucleic bases has a profound effect on the stability of the thymine valence anion: the anionic 5'-CTC-3' (6.0 kcal/mol) sequence is the most stable configuration, and the 5'-GTG-3' (-8.0 kcal/mol) trimer anion is the most unstable species. On the basis of obtained results, one can propose DNA sequences that are different in their vulnerability to damage by low energy electron.