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 alpha-oxy-substituted derivatives through Norrish-type I cleavage.
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-O(t)Bu) lead to carbon-centered radicals by alpha 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 O(2), 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 alpha cleavage of the triplet ketone and subsequent O(2) 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.
Adam
Waldemar
W
Contribution from the Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany. adam@chemie.uni-wuerzberg.de
Arnold
Markus A
MA
Nau
Werner M
WM
Pischel
Uwe
U
Saha-Möller
Chantu R
CR
D000098:Acetophenones / Q000737:chemistry*; D001577:Benzophenones / Q000737:chemistry; D004249:DNA Damage; D003839:Deoxyadenosines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D010084:Oxidation-Reduction; D010782:Photolysis; D017382:Reactive Oxygen Species / Q000737:chemistry
D000098:Acetophenones; D001577:Benzophenones; D003839:Deoxyadenosines; D017382:Reactive Oxygen Species; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; C047723:benzophenone; D003849:Deoxyguanosine