Structural behavior of sugar radicals formed by proton transfer reaction of deoxycytidine cation radical: detailed view from NBO analysis.

The cation radicals of DNA constituents generated by the ionizing radiation initiate the alteration of the bases, which is one main type of cytotoxic DNA lesions. These cation radical spices are known for their role in producing nucleic acid strand break, and it is important to identify the cation radical formation at particular atomic site in these molecules so that the major pathway for the nucleic acid damage may be trapped. In the present study, we explored theoretically energetic, structural, and electronic properties of the possible radicals formed via proton atom abstraction at various sites of sugar part of deoxycytidine cation radical by employing density functional theory at B3LYP/6-311++G (d,p) level. The computation revealed 0.0-22.6 kcal/mol energy disparity in these radicals. Radical-centered carbon increases the extent of bonding with its adjacent atoms. This tendency should be important in predicting the reactivity of sugar-based radicals. Based on DFT calculations, sugar radicals of deoxycytidine have following stability order: raH1′ > raH2′ > raH4′ > raH3′ > raH5′ > raO5′H > raO3′H. Furthermore, influence of cation radical formation on acidities of multiple sites in deoxycytidine nucleosides was investigated. For instance upon cation radical formation, ΔH of O3′H and O5′H sites of deoxycytidine varies from 348.6 and 351.5 to 228.8 and 227.5 kcal/mol, respectively. [ABSTRACT FROM AUTHOR]