Hydroxyl Radical (OH•) Reaction with Guanine in an Aqueous Environment: A DFT Study

摘要

The reaction of hydroxyl radical (OH^•) with DNA accounts for about half of radiation-induced DNA damage in living systems. Previous literature reports point out that the reaction of OH^• with DNA proceeds mainly through the addition of OH^• to the C=C bond of the DNA bases. However, recently it has been reported that the principal reaction of OH^• with dGuo (deoxyguanosine) is the direct hydrogen atom abstraction from its exocyclic amine group rather than addition of OH^• to the C=C bond. In the present work, these two reaction pathways of OH^• attack on guanine (G) in the presence of water molecules (aqueous environment) are investigated using the density functional theory (DFT) B3LYP method with 6-31G* and 6-31++G** basis sets. The calculations show that the initial addition of the OH^• at C4=C5 double bond of guanine is barrier free and the adduct radical (G-OH^•) has only a small activation barrier of ca. 1 – 6 kcal/mol leading to the formation of a metastable ion-pair intermediate (G^•+---OH⁻). The formation of ion-pair is a result of the highly oxidizing nature of the OH^• in aqueous media. The resulting ion-pair (G^•+---OH⁻) deprotonates to form H2O and neutral G radicals favoring G(N1-H)^• with an activation barrier of ca. 5 kcal/mol. The overall process from the G(C4)-OH^• (adduct) to G(N1-H)^• and water is found to be exothermic in nature by more than 13 kcal/mol. (G-OH^•), (G^•+---OH⁻), and G(N1-H)^• were further characterized by the CAM-B3LYP calculations of their UV-visible spectra and good agreement between theory and experiment is achieved. Our calculations for the direct hydrogen abstraction pathway from N1 and N2 sites of guanine by the OH^• show that this is also a competitive route to produce G(N2-H)^•, G(N1-H)^• and H2O.