Nitrogen dioxide as an oxidizing agent of 8-oxo-7,8-dihydro-2′-deoxyguanosine but not of 2′-deoxyguanosine

The redox reactions of guanine and its widely studied oxidation product, the 8-oxo-7,8-dihydro derivative, are of significant importance for understanding the mechanisms of oxidative damage in DNA. Employing 2′-deoxyguanosine 5′-monophosphate (dGMP) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in neutral aqueous solutions as model systems, we have used nanosecond laser flash photolysis to demonstrate that neutral radicals, dGMP(-H)•, derived by the one-electron oxidation and deprotonation of dGMP, can oxidize nitrite anions (NO₂^-) to the nitrogen dioxide radical •NO₂. In turn, we show that •NO₂ can give rise to a one-electron oxidation of 8-oxo-G, but not of dGMP. The one-electron oxidation of dGMP was initiated by a radical cation generated by the laser pulse-induced photoionization of a pyrene derivative with enhanced water solubility, 7,8,9,10-tetrahydroxytetrahydrobenzo[α]pyrene (BPT). The dGMP(-H)• neutral radicals formed via deprotonation of the dGMP^•+ radical cations and identified by their characteristic transient absorption spectrum (λ_max ∼ 310 nm) oxidize nitrite anions with a rate constant of(2.6 ± 0.3) × 10⁶ M^-1 s^-1. The 8-oxo-dG is oxidized by •NO₂ with a rate constant of (5.3 ± 0.5) × 10⁶ M^-1 s^-1. The 8-oxo-dG(-H)• neutral radicals thus generated are clearly identified by their characteristic transient absorption spectra (λ_max ∼ 320 nm). The rate constant of 8-oxo-dG oxidation (k₁₂) by the •NO₂ one-electron oxidant (the •NO₂/NO₂^- redox potential, E° ≈ 1.04 V vs NHE) is lower than k₁₂ for a series of oxidizing aromatic radical cations with known redox potentials. The k₁₂ values for 8-oxo-dG oxidation by different aromatic radical cations derived from the photoionization of their parent compounds depend on the redox potentials of the latter, which were in the range of 0.8-1.6 V versus NHE. The magnitude of k₁₂ gradually decreases from a value of 2.2 × 10⁹ M^-1 s^-1 (E° = 1.62 V) to 5.8 × 10⁸ M^-1 s^-1 (E° = 1.13 V) and eventually to 5 × 10⁷ M^-1 s^-1 (E° = 0.91 V). The implications of these results, including the possibility that the redox cycling of the •NO₂/NO₂^- species can be involved in the further oxidative damage of 8-oxo-dG in DNA in cellular environments, are discussed.