Structure-dependent reactivity of oxyfunctionalized acetophenones in the photooxidation of DNA: base oxidation and strand breaks through photolytic radical formation (spin trapping, EPR spectroscopy, transient kinetics) versus photosensitization (electron transfer, hydrogen-atom abstraction).
The photooxidative damage of DNA, specifically guanine oxidation and strand-break formation, by sidechain-oxyfunctionalized acetophenones (hydroxy, methoxy, tert-butoxy and acetoxy derivatives), has been examined. The involvement of triplet-excited ketones and their reactivity towards DNA has been determined by time-resolved laser-flash spectroscopy. The generation of carbon-centered radical species upon Norrish-type I cleavage has been assessed by spin-trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide, coupled with electron paramagnetic resonance spectroscopy. The observed DNA-base oxidation and strand-break formation is discussed in terms of the peroxyl radicals derived from the triplet-excited ketones by alpha cleavage and molecular oxygen trapping, as well as direct interaction of the excited states by electron transfer and hydrogen-atom abstraction. It is concluded that acetophenone derivatives, which produce radicals upon photolysis, in particular the hydroxy (AP-OH) and tert-butoxy (AP-O(t)Bu) derivatives, are more effective in oxidizing DNA.
Adam
W
W
Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany. adam@chemie.uni-wuerzburg.de
Arnold
M A
MA
Nau
W M
WM
Pischel
U
U
Saha-Möller
C R
CR
D000098:Acetophenones / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010777:Photochemistry; D010782:Photolysis; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000737:chemistry; D013997:Time Factors
D000098:Acetophenones; D007659:Ketones; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; C038699:acetophenone