Abstract: Molecular geometries and electronic structures of adducts between the hydroxyl radical and the cytosine of 2’-deoxycytidine-5’-monophosphate acid (dCMP) were investigated by density functional theory, B3LYP/DZP++. Computational results reveal that the relative stability sequence of single hydroxyl radical adducts of cytosine of dCMP is C5>C6>>C4≥C2. The C5 atom of dCMP is most reactive for addition of the first hydroxyl radical whereas the C6 atomis not only the next most reactive site for addition of the first hydroxyl radical but also the second reactive site forthe second hydroxyl radical addition when one dCMP molecule is attacked by multiple hydroxyl radicals. This sequence was established by analyses of their stabilities, spin densities, electrostatic potentials of adducts and electron densities, electrostatic potentials, and charge distributions of dCMP. Once the C2-adduct of dCMP is produced either a fatal gene mutation during DNA replication or a DNA-DNA, DNA-protein cross-link leading to more complicated damage of DNA might occur. In contrast, neither the C5- nor C6-adduct of dCMP has a significant effect on the stability of DNA.

Key words: 2’-Deoxycytidine-5’-monophosphate acid, Hydroxyl radical adduct, Addition reaction, Gene mutation