A Reevaluation of the Ambident Reactivity of the Guanine Moiety Towards Hydroxyl Radicals
ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy.Angewandte Chemie International Edition (Impact Factor: 11.26). 03/2009; 48(12):2214-7. DOI: 10.1002/anie.200805372
Radically different: Contrary to previous proposals, the main reaction of the HO(*) radical with guanosine or 2'-deoxyguanosine is the hydrogen abstraction from the NH(2) moiety to give a guanyl radical. This radical, characterized by a broad band in the visible region (around 610 nm), undergoes tautomerization to the most stable isomer.
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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.Journal of the American Chemical Society 10/2009; 131(43):15895-902. DOI:10.1021/ja9065464 · 12.11 Impact Factor
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ABSTRACT: One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alternative approach for the site specific, independent generation of the guanine radical, utilizing N-hydroxypyrid-2(1H)-one as a photolabile modifier of guanine, is proposed. Novel photolabile 6-[(1-oxido-2-pyridinyl)oxo]-6-deoxy- and 2',6-dideoxy-guanosine derivatives capable of generating the neutral guanine radical (G(-H)*) upon photolysis were synthesized and characterized. The generation of G(-H)* proceeds through homolysis of the N-O bond and was confirmed through continuous photolysis product analysis and trapping studies, as well as laser flash photolysis experiments.Organic & Biomolecular Chemistry 12/2009; 7(23):4965-72. DOI:10.1039/b909138f · 3.56 Impact Factor
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