4-TERT-BUTYLPEROXYMETHYL-9-METHOXYPSORALEN AS INTERCALATING PHOTOCHEMICAL ALKOXYL-RADICAL SOURCE FOR OXIDATIVE DNA-DAMAGE

We describe the synthesis of a novel psoralen peroxide I that generate s on irradiation (350 nm) alkoxyl radicals, namely tert-butoxyl radica ls, as confirmed by electron spin resonance studies with the spin trap 5,5-dimethyl-pyrroline-N-oxide. The radical source intercalates into the DNA, which has been demonstrated by linear-flow-dichroism measurem ents. Thus, the alkoxyl radicals are formed advantageously directly in the DNA matrix. In supercoiled pBR322 DNA, the generation of strand b reaks by the photochemically or metal-catalyzed generated alkoxyl radi cals is demonstrated, Photosensitization by the psoralen chromophore w as excluded because similar substances that do not release radicals ca used no DNA damage, nor were the photoproducts of the peroxide 1 activ e. With calf thymus DNA, 8-oxoGua and small amounts of guanidine-relea sing products, e.g. oxazolone, were observed. However, in these reacti ons the photoproduct also displayed some DNA-oxidizing capacity.