Generation of 8-oxo-7,8-dihydroguanine in G-Quadruplexes Models of Human Telomere Sequences by One-electron Oxidation

Abstract

The mechanistic aspects of one-electron oxidation of G-quadruplexes in the basket (Na⁺ ions) and hybrid (K⁺ ions) conformations were investigated by transient absorption laser kinetic spectroscopy and HPLC detection of the 8-oxo-7,8-dihydroguanine (8-oxoG) oxidation product. The photo-induced one-electron abstraction from G-quadruplexes was initiated by sulfate radical anions (SO₄ ˙^- ) derived from the photolysis of persulfate ions by 308 nm excimer laser pulses. In neutral aqueous solutions (pH 7.0), the transient absorbance of neutral guanine radicals, G(-H)˙, is observed following the complete decay of SO₄ ˙^- radicals (~10 μs after the actinic laser flash). In both basket and hybrid conformations, the G(-H)˙ decay is biphasic with one component decaying with a lifetime of ~0.1 ms, and the other with a lifetime of 20-30 ms. The fast decay component (~0.1 ms) in G-quadruplexes is correlated with the formation of 8-oxoG lesions. We propose that in G-quadruplexes, G(-H)˙ radicals retain radical cation character by sharing the N1-proton with the O⁶ -atom of G in the [G˙⁺ : G] Hoogsteen base pair; this [G(-H)˙: H⁺ G $\rightleftarrows$ G˙⁺ : G] leads to the hydration of G˙⁺ radical cation within the millisecond time domain, and is followed by the formation of the 8-oxoG lesions.