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

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 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.