Formation of S鈥揅l Phosphorothioate Adduct Radicals in dsDNA S-Oligomers: Hole Transfer to Guanine vs Disulfide Anion Radical Formation

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• 作者：Amitava Adhikary ; Anil Kumar ; Brian J. Palmer ; Andrew D. Todd ; Michael D. Sevilla
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：August 28, 2013
• 年：2013
• 卷：135
• 期：34
• 页码：12827-12838
• 全文大小：569K
• 年卷期：v.135,no.34(August 28, 2013)
• ISSN：1520-5126

文摘

In phosphorothioate-containing dsDNA oligomers (S-oligomers), one of the two nonbridging oxygen atoms in the phosphate moiety of the sugar鈥損hosphate backbone is replaced by sulfur. In this work, electron spin resonance (ESR) studies of one-electron oxidation of several S-oligomers by Cl₂^{鈥⑩€?/sup> at low temperatures are performed. Electrophilic addition of Cl₂鈥⑩€?/sup> to phosphorothioate with elimination of Cl鈥?/sup> leads to the formation of a two-center three-electron 蟽2蟽*1-bonded adduct radical (-P-S-虈Cl). In AT S-oligomers with multiple phosphorothioates, i.e., d[ATATAsTsAsT]₂, -P-S-虈Cl reacts with a neighboring phosphorothioate to form the 蟽2蟽*1-bonded disulfide anion radical ([-P-S-虈S-P-]鈭?/sup>). With AT S-oligomers with a single phosphorothioate, i.e., d[ATTTAsAAT]₂, reduced levels of conversion of -P-S-虈Cl to [-P-S-虈S-P-]鈭?/sup> are found. For guanine-containing S-oligomers containing one phosphorothioate, -P-S-虈Cl results in one-electron oxidation of guanine base but not of A, C, or T, thereby leading to selective hole transfer to G. The redox potential of -P-S-虈Cl is thus higher than that of G but is lower than those of A, C, and T. Spectral assignments to -P-S-虈Cl and [-P-S-虈S-P-]鈭?/sup> are based on reaction of Cl₂鈥⑩€?/sup> with the model compound diisopropyl phosphorothioate. The results found for d[TGCGsCsGCGCA]₂ suggest that [-P-S-虈S-P-]鈭?/sup> undergoes electron transfer to the one-electron-oxidized G, healing the base but producing a cyclic disulfide-bonded backbone with a substantial bond strength (50 kcal/mol). Formation of -P-S-虈Cl and its conversion to [-P-S-虈S-P-]鈭?/sup> are found to be unaffected by O₂, and this is supported by the theoretically calculated electron affinities and reduction potentials of [-P-S-S-P-] and O₂.}