The Equally Important Role of Adenine Derivatives to That of Pyrimidine Derivatives in Near-0 eV Electron-Induced DNA Lesions

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• 作者：Shoushan Wang ; Peiwen Zhao ; Changzhe Zhang and Yuxiang Bu
• 刊名：ChemPhysChem
• 出版年：2016
• 出版时间：June 3, 2016
• 年：2016
• 卷：17
• 期：11
• 页码：1669-1677
• 全文大小：1303K
• ISSN：1439-7641

文摘

The role of adenine (A) derivatives in DNA damage is scarcely studied due to the low electron affinity of base A. Experimental studies demonstrate that low-energy electron (LEE) attachment to adenine derivatives complexed with amino acids induces barrier-free proton transfer producing the neutral N₇-hydrogenated adenine radicals rather than conventional anionic species. To explore possible DNA lesions at the A sites under physiological conditions, probable bond ruptures in two models—N₇-hydrogenated 2′-deoxyadenosine-3′-monophosphate (3′-dA(N7H)MPH) and 2′-deoxyadenosine-5′-monophosphate (5′-dA(N7H)MPH), without and with LEE attachment—are studied by DFT. In the neutral cases, DNA backbone breakage and base release resulting from C_3′−O_3′ and N₉−C_1′ bond ruptures, respectively, by an intramolecular hydrogen-transfer mechanism are impossible due to the ultrahigh activation energies. On LEE attachment, the respective C_3′−O_3′ and N₉−C_1′ bond ruptures in [3′-dA(N7H)MPH]⁻ and [5′-dA(N7H)MPH]⁻ anions via a pathway of intramolecular proton transfer (PT) from the C_2′ site of 2′-deoxyribose to the C₈ atom of the base moiety become effective, and this indicates that substantial DNA backbone breaks and base release can occur at non-3′-end A sites and the 3′-end A site of a single-stranded DNA in the physiological environment, respectively. In particular, compared to the results of previous theoretical studies, not only are the electron affinities of 3′-dA(N7H)MPH and 5′-dA(N7H)MPH comparable to those of hydrogenated pyrimidine derivatives, but also the lowest energy requirements for the C_3′−O_3′ and N₉-glycosidic bond ruptures in [3′-dA(N7H)MPH]⁻ and [5′-dA(N7H)MPH]⁻ anions, respectively, are comparable to those for the C_3′−O_3′ and N₁-glycosidic bond cleavages in corresponding anionic hydrogenated pyrimidine derivatives. Thus, it can be concluded that the role of adenine derivatives in single-stranded DNA damage is equally important to that of pyrimidine derivatives in an irradiated cellular environment.