Enantioselectively generating imidazolone dIz by the chiral DNA intercalating and "light-switching" Ru(II) polypyridyl complex via a novel flash-quench method.

The 2-aminoimidazolone is a major and ubiquitous in vitro product of guanine oxidation. The flash-quench method, combining spectroscopy and product analysis, offers a novel and tunable approach to study guanine oxidation on double helical DNA. Herein we found that imidazolone dIz (2-amino-5-[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-4H-imidazole-4-one) and dZ (2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone) were the major oxidation products of double-strand DNA from the visible-light irradiation of the well-known DNA intercalating and light-switching Ru(OP) ₂ dppz ²⁺ (OP = 1,10-phenanthroline, dppz = dipyrido [3,2-a:2',3'-c]phenazine) in the presence of a typical quencher methyl viologen (MV ²⁺ ). Using ESR spin-trapping method, the radical intermediate MV ^•+ with typical hyperfine pattern was detected which indicated the successful formation of the corresponding Ru ³⁺ intercalated oxidant. The formation of dIz and dZ decreased markedly with the addition of nitrotetrazolium blue chloride (NBT), a typical O ₂ ^•- reactant. With a more specific and highly sensitive O ₂ ^•- probe CT02-H, its ESR signal decayed rapidly in the presence of Ru(OP) ₂ dppz ²⁺ and MV ²⁺ , suggesting that O ₂ ^•- was indeed produced. More interestingly, enantio-selective generation of oxidation products from dsDNA was observed with the two chiral forms of Ru(OP) ₂ dppz ²⁺ . This represents the first report that the flash-quench technique with MV ²⁺ as the quencher can oxidize dsDNA effectively to form dIz and dZ via the Ru ³⁺ /O ₂ ^•- mediated mechanism. Our new findings provide a novel method to generate two radicals simultaneously, G (-H) ^• and O ₂ ^•- , in close proximity to one another in dsDNA.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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