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.