Effect of nucleobase sequence on the proton-transfer reaction and stability of the guanine–cytosine base pair radical anion

The formation of base pair radical anions is closely related to many fascinating research fields in biology and chemistry such as radiation damage to DNA and electron transport in DNA. However, the relevant knowledge so far mainly comes from studies on isolated base pair radical anions, and their behavior in the DNA environment is less understood. In this study, we focus on how the nucleobase sequence affects the properties of the guanine–cytosine (GC) base pair radical anion. The energetic barrier and reaction energy for the proton transfer along the N1(G)–H⋯N3(C) hydrogen bond and the stability of GC˙− (i.e., electron affinity of GC) embedded in different sequences of base-pair trimer were evaluated using density functional theory. The computational results demonstrated that the presence of neighboring base pairs has an important influence on the behavior of GC˙− in the gas phase. The excess electron was found to be localized on the embedded GC and the charge leakage to neighboring base pairs was very minor in all of the investigated sequences. Accordingly, the sequence behavior of the proton-transfer reaction and the stability of GC˙− is chiefly governed by electrostatic interactions with adjacent base pairs. However, the effect of base stacking, due to its electrostatic nature, is severely screened upon hydration, and thus, the sequence dependence of the properties of GC˙− in aqueous environment becomes relatively weak and less than that observed in the gas phase. The effect of geometry relaxation associated with neighboring base pairs as well as the possibility of proton transfer along the N2(G)–H⋯O2(C) channel have also been investigated. The implications of the present findings to the electron transport and radiation damage of DNA are discussed.