Comparison of Isoelectronic 8-HO-G and 8-NH₂-G Derivatives in Redox Processes

Abstract

8-Oxo-7,8-dihydroguanine (8-oxo-G) is the major lesion of oxidatively generated DNA damage. Despite two decades of intense study, several fundamental properties remain to be defined. Its isoelectronic 8-aminoguanine (8-NH(2)-G) has also received considerable attention from a biological point of view, although its chemistry involving redox processes remains to be discovered. We investigated the one-electron oxidation and one-electron reduction reactions of 8-oxo-G and 8-NH(2)-G derivatives. The reactions of hydrated electrons (e(aq)(-)) and azide radicals (N(3)(*)) with both derivatives were studied by pulse radiolysis techniques, and the transient absorption spectra were assigned to specific tautomers computationally by means of time-dependent DFT (TD-B3LYP/6-311G**//B1B95/6-31+G**) calculations. The protonated electron adducts of 8-NH(2)-G and 8-oxo-G showed a substantial difference in their absorption spectra, the unpaired electron being mainly delocalized in the imidazolyl ring and in the six-membered ring, respectively. On the other hand, the deprotonated forms of one-electron oxidation of 8-NH(2)-G and 8-oxo-G showed quite similar spectral characteristics. In a parallel study, the one-electron reduction of 8-azidoguanine (8-N(3)-G) afforded the same transient of one-electron oxidation of 8-NH(2)-G, which represents another example of generation of one-electron oxidized guanine derivatives under reducing conditions. Moreover, the fate of transient species was investigated by radiolytic methods coupled with product studies and allowed self- and cross-termination rate constants associated with these reactions to be estimated.

Computational Study of the Radical Mediated Mechanism of the Formation of C8, C5, and C4 Guanine:Lysine Adducts in the Presence of the Benzophenone Photosensitizer

“…Compared to the extensive experimental investigations, there are only a limited number of computational studies related to guanine:lysine cross-links. , Jena and Mishra compared the gas phase stabilities of noncovalently bound guanine:lysine complexes in different charge states using density functional and Møller–Plesset perturbation theories . Their study showed that the spin and charge in a guanine:lysine radical cation complex were concentrated on the guanine subunit, which is consistent with the experimental observation that the ionization potential of guanine is lower than that of lysine. , The addition of ammonia to oxidized guanine forming 8-aminoguanine has been studied both computationally and experimentally . To the best of our knowledge, a full computational study of potential mechanisms for covalent guanine:lysine cross-link formation has not been reported yet.…”

Converging Fate of the Oxidation and Reduction of 8-Thioguanosine

“…Once the tautomeric radical E formed, this could lead back to the starting material 1 . In fact, this has been reported for similar intermediates for the other studied guanosine derivatives, which resulted in regeneration of the substrate with a still unclear mechanism [31,52]. This pathway could explain the absence of further consumption of 8-TG in the predominant presence of HO • radicals.…”

“…This pathway could explain the absence of further consumption of 8-TG in the predominant presence of HO • radicals. Additionally, the intermediate E could be directly formed by Br 2 •− and N 3 • and provide regeneration of 1 in the same fashion, explaining the comparable results in the presence of these two radical species [31,51,52].…”

“…In fact, in all the reactions we could observe similar results to the ones obtained in the previous experiments in terms of G values, while no further consumption of the substrate was achieved via side product formation. On the basis of our strong background of radical chemistry of guanosine derivatives [31,47,48,49,50,51,52], it was established that HO • radicals could perform hydrogen abstraction predominantly on the exocyclic NH 2 group [48,49,50], leading to the radical intermediate D (Scheme 5). This species could undergo tautomerization to the more stable radical E .…”

The Antioxidant Activity of Quercetin in Water Solution

“…Subsequently, we referred to the time-resolved UV–vis spectra obtained by pulse radiolysis by Jovanovic and co-workers during the reaction of quercetin with N 3 • radical in water at various pH [38]. In order to assign the experimental spectra to specific phenoxyl radicals of quercetin, we matched them with the spectra that we calculated for any transient, using TD-DFT methods, which are emerging as powerful tools to investigate radical reactions by allowing the assignment of transient UV–vis spectra [39,40,41,42].…”