Direct Formation of the C5′-Radical in the Sugar–Phosphate Backbone of DNA by High-Energy Radiation
2012
Adhikary, Amitava | Becker, David | Palmer, Brian J. | Heizer, Alicia N. | Sevilla, Michael D.
Neutral sugar radicals formed in DNA sugar–phosphate backbone are well-established as precursors of biologically important damage such as DNA strand scission and cross-linking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5′ (C5′•) is one of the most abundant (ca. 30%) sugar radicals formed by γ- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar–phosphate backbone, ESR and theoretical (DFT) studies of γ-irradiated dimethyl phosphate were carried out. CH₃OP(O₂–)OCH₂• is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. The formation of CH₃OP(O₂–)OCH₂• is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5′• found in DNA and of CH₃OP(O₂–)OCH₂• do not show an observable β-phosphorus hyperfine coupling (HFC). Furthermore, C5′• found in DNA does not show a significant C4′-H β-proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorus HFC in CH₃OP(O₂–)OCH₂• shows that in its minimum energy conformation, CH₃OP(O₂–)OCH₂•, has a negligible β-phosphorus HFC. On the basis of these results, the formation of radiation-induced C5′• is proposed to occur via a very rapid deprotonation from the directly ionized sugar–phosphate backbone, and the rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar–phosphate backbone to the DNA bases. Moreover, C5′• in irradiated DNA is found to be in a conformation that does not exhibit β-proton or β-phosphorus HFCs.
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