Interaction of singlet oxygen and superoxide radical anion with guanine and formation of its mutagenic modification 8-oxoguanine

Formation of 8-oxoguanine (8OG) from guanine in biological systems is known to cause lethal mutation and cancer. It has been suggested earlier, on the basis of experimental studies, that the oxygen molecule in its lowest singlet excited state (O-1(2)) plays an important role in the formation of 80G. In order to understand the possible mechanisms in this context, B3LYP/6-31+G* and MP2/6-31+G* calculations were carried out on the structures and stabilities of different molecules and complexes involved in the formation of 80G. All the molecules, complexes, and transition states studied in the present report were solvated in aqueous media. Guanine has been found to make a strong complex with O-1(2), with the latter species located above the imidazole ring plane, and the complex of guanine with O-3(2) is much weaker than that with O-1(2). Transition state calculations were carried out to study formation of 7,8-dihydro,8-hydroxyguanine (80HG) and 2-oxo-imidazole. It has been shown that 80G can be formed in two different ways: (i) due to interaction of the radical cation of guanine with O-2(-) where 80HG complexed with O-1(2) would occur as an intermediate, and (ii) due to interaction of guanine with O-1(2) leading to the formation of guanine hydroperoxide that would react with a water molecule in the presence of two O-1(2) molecules serving as a source of energy to overcome the barrier. It is shown that because the interaction strengths of O-3(2) and O-1(2) with other molecules, e.g., guanine, are very different, a crossing of their potential energy surfaces takes place in both gas phase and aqueous media, as a result of which the lifetime of O-1(2) is strongly decreased. (c) 2004 Wiley Periodicals, Inc.