Hydroxyl Radical Addition to Thymine and Cytosine and Photochemistry of the Adducts at the C6 Position

Abstract

AbstractOxidative damage can compromise the biological function of DNA/RNA nucleobases. Among the several agents that can cause oxidative damage in cells, the hydroxyl radical (.OH) is considered one of the most reactive species able to add at either the C5 or C6 positions of the C5=C6 double bond of pyrimidine nucleobases. The present work tackles, firstly, the ground state reactivity of the thymine and cytosine nucleobases with .OH using the DFT method. We find that the most favorable attack occurs at the C5 atom in both cases, although C6 is also probable, as observed in previous experimental studies. Secondly, the photochemistry of the C6OH. and T6OH. adducts (which can absorb visible light) is studied at the CASPT2//CASSCF level of theory. In C6OH., the most probable decay corresponds to the return to the initial geometry, whereas in T6OH., distinct processes can compete: (i) return to the Franck‐Condon region, (ii) deactivation by fluorescence emission, (iii) reversion of the oxidation lesion and (iv) the formation of an unstable ketene photoproduct reported herein for the first time.