Guanine Oxidation by Electron Transfer: One‐ versus Two‐Electron Oxidation Mechanism

Abstract

The degeneracy of the guanine radical cation, which is formed in DNA by oxidation of guanine by electron transfer, was studied by a detailed analysis of the oxidation products of guanine on oligonucleotide duplexes and by labeling experiments. It was shown that imidazolone, the major product of guanine oxidation, is formed through a one-electron oxidation process and incorporates one oxygen atom from O2. The formation of 8-oxo-7,8-dihydroguanine by a two-electron oxidation process was a minor pathway. The two-electron oxidation mechanism was also evidenced by the formation of a tris(hydroxymethyl)aminomethane adduct.

Comparison of transition metal-mediated oxidation reactions of guanine in nucleoside and single-stranded oligodeoxynucleotide contexts

“…It was suggested that the compound arises from hydroxylation at C5 of a (G-H) + intermediate, leading to an unstable compound with one labeled oxygen atom from H 2 18 O added at C5. This intermediate was expected to rearrange at physiological pH into an Sp-like structure (Scheme 3) that would be sensitive to hydrolytic ring opening [62]. The Rokita laboratory also found the mass of G+34 as the major product of DNA oxidation with a dinuclear copper complex, [Cu 2 II (PD′O)(H 2 O) 2 ] 3+ where PD′OH is a pyridylalkylamine containing binucleating ligand [63].…”

Photolysis and Thermolysis of Platinum(IV) 2,2′‐Bipyridine Complexes Lead to Identical Platinum(II)–DNA Adducts

“…This method is highly sensitive and has previously allowed us to detect about 1 % of oxidative DNA damage. [39,40] Under these experimental conditions the short ODN was single-stranded.…”

“…The retention times and the mass data of oxidized ODN were known from previous work on 5'-CAGCTG. [39,40] Formation of an oxidized oligonucleotide strand (even 1 % yield, 0.1 mm) would have been detected by the method of analysis. The yield of www.chemeurj.org spontaneous reduction determines the subsequent concentration of diffusible oxidative species from the released axial ligands (HOCl or Cl 2 ).…”

Hawkins DS, Rajendran JG, Conrad III EU, Bruckner JD, Eary JF. Evaluation of chemotherapy response in pediatric bone sarcomas by [F‐18]‐fluorodeoxy‐D‐glucose positron emission tomography. Cancer. (2002) 94(12):3277–3284.

“…The retention times and the mass data of oxidized ODN were known from previous work on 5′‐CAGCTG 39. 40 Formation of an oxidized oligonucleotide strand (even 1 % yield, 0.1 μ M ) would have been detected by the method of analysis. The yield of spontaneous reduction determines the subsequent concentration of diffusible oxidative species from the released axial ligands (HOCl or Cl 2 ).…”