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

Abstract

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 (¹O₂) plays an important role in the formation of 8OG. 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 8OG. 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 ¹O₂ with the latter species located above the imidazole ring plane, and the complex of guanine with ³O₂ is much weaker than that with ¹O₂. Transition state calculations were carried out to study formation of 7,8-dihydro,8-hydroxyguanine (8OHG) and 2-oxo-imidazole. It has been shown that 8OG can be formed in two different ways: (i) due to interaction of the radical cation of guanine with O²_ where 8OHG complexed with ¹O₂ would occur as an intermediate, and (ii) due to interaction of guanine with ¹O₂ leading to the formation of guanine hydroperoxide that would react with a water molecule in the presence of two ¹O₂ molecules serving as a source of energy to overcome the barrier. It is shown that because the interaction strengths of ³O₂ and ¹O₂ 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 ¹O₂ is strongly decreased.