Quantum chemical study for radical-induced DNA effects and damage.

Differences in molecular interaction between bases (adenine (A), guanine (G), and cytosine (C)) and the methyl (Me)-radical were investigated by perturbation analysis using the quantum chemical method. Part of the source of damage to the DNA was elucidated at the molecular level. In the reaction of each of the saccharide derivatives (dA, dG, and dC) with Me-radical, the reactivity of dG (≈dA) is more than about 10 times larger than that of dC. Therefore, it is expected that the base G (and A) was more than about 10 times than the base C in radical-reactivity of the base. For the reaction of dA and dG with the radical, the C(8) site of the partial purine ring of dA and dG, and the C(5) site of the pyrimidine ring of dC were the main reaction sites for methylation. In the reaction of DNA composed of hydrogen-bonded base pairs G-C and A-T with the radical, the purine ring in the constituent base G reacted preferentially with the radical to yield 8-methyl-guanines.