The reactivity of the 5‐formylcytosine with hydroxyl radical: A theoretical perspective

Hydroxyl radical (?OH) damages DNA/RNA by attacking pyrimidine nucleobases through the addition reaction and H‐atom abstraction. It may attack on the new cytosine derivative (5‐formylCytosine [5‐fCyt]) causing DNA oxidative damage, whereas the study of the related mechanism is still in its infancy. In the present work, 2 distinct mechanisms of ?OH‐mediated 5‐fCyt at the complete basis set methods (CBS‐QB3) and CBS‐QB3/polarized continuum model approaches have firstly been explored, the addition reaction (paths R1 ~ R3) and the abstraction reaction (paths R4 ~ R6), respectively, and it shows that the addition of ?OH to the C5═C6 double bond of 5‐fCyt is more favourable than other reactions, indicating that the ?OH addition to the C5 and C6 atoms have relatively high probability to happen. The proportion of the C5 and C6 adducts is large and may be detectable experimentally, which is in agreement with the conclusions of ?OH‐mediated cytosine reaction reported experimentally and theoretically. These hint that the new DNA base (5‐fCyt) is easily damaged when exposed the surrounding of ?OH environment. Therefore, the reducing free radical production or the addition of some antioxidants should be taken in embryonic stem cells to resistance DNA damage. Our results provide some evidences between 5‐fCyt and tumor development for the experimental scientists.