A Comparative Photomechanistic Study (Spin Trapping, EPR Spectroscopy, Transient Kinetics, Photoproducts) of Nucleoside Oxidation (dG and 8-oxodG) by Triplet-Excited Acetophenones and by the Radicals Generated from α-Oxy-Substituted Derivatives through Norrish-Type I Cleavage

• Published in: Journal of the American Chemical Society 2002-04, Vol.124 (15), p.3893-3904
• Main Authors: Adam, Waldemar, Arnold, Markus A, Nau, Werner M, Pischel, Uwe, Saha-Möller, Chantu R
• Format: Article
• Language: English
• Subjects: Acetophenones - chemistry; Benzophenones - chemistry; Biological and medical sciences; Chemistry; Deoxyadenosines - chemistry; Deoxyguanosine - chemistry; DNA Damage; Electron Spin Resonance Spectroscopy; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General and physical chemistry; Kinetics; Molecular biophysics; Oxidation-Reduction; Photochemistry; Photochemistry. Photosynthesis. Bioluminescence; Photolysis; Physical chemistry of induced reactions (with radiations, particles and ultrasonics); Radiation-biomolecule interaction; Reactive Oxygen Species - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja017600y

The photooxidation of 2‘-deoxyguanosine (dG) and its derivative 8-oxo-7,8-dihydro-2‘-deoxyguanosine (8-oxodG) by a series of acetophenones (AP-X) and benzophenone (BP) has been studied.The favorable absorption characteristics of the benzoyl chromophore enables time-resolved spectroscopy of the triplet ketones to assess their quenching kinetics by dG and 8-oxodG. Whereas the photolysis of acetophenone (AP), 2-acetoxyacetophenone (AP-OAc), and benzophenone (BP) does not produce radicals (group A ketones), the oxymethyl-substituted derivatives 2-hydroxyacetophenone (AP-OH) and 2-tert-butoxyacetophenone (AP-OtBu) lead to carbon-centered radicals by α cleavage (group B ketones). For the latter ketones, this was confirmed by EPR studies with the spin trap 5,5-dimethylpyrroline N-oxide (DMPO) and by their triplet lifetimes that were shorter than those for the unsubstituted acetophenone. Both groups of ketones photooxidize dG and 8-oxodG; the oxidation products are spiroiminodihydantoin and guanidine-releasing products (GRP) in the case of dG and AP-OH also 8-oxodG. In the presence of O2, the photooxidation by the group A ketones is efficient at high dG or 8-oxodG concentrations, whereas the group B ketones photooxidize dG and 8-oxodG also at low substrate concentrations. These results imply that peroxyl radicals are responsible for the photooxidation by the group B ketones, which are formed by α cleavage of the triplet ketone and subsequent O2 trapping of the carbon-centered radicals. At higher dG concentrations, direct electron transfer from dG to the triplet ketone, as observed for the group A ketones, competes with the radical activity.