DNA cleavage induced by photoirradiation of coenzyme B12 and organocobaloximes without dioxygen

Homolytic cobalt–carbon bond cleavages of methylcobalamin (coenzyme B12) and a B12 analogue, [(DH)2(CH3)Co(py)] ((DH)2 = bis(dimethylglyoximate), py = pyridine) by UVA irradiation induced effective DNA strand scission by generated methyl radical under anaerobic conditions. The efficiency of DNA strand scission is drastically changed depending on the type of generated radicals. For example, the photoexcitation of 5′-deoxyladenosylcobalamin (one of coenzyme B12) under anaerobic condition results in less effective DNA cleavage. No DNA cleavage has occurred under photoirradiation of (DH)2(PhCH2)Co(py), because the reactivity of benzyl radical formed by Co–C bond cleavage is much lower than that of methyl radical. The photoreactivity of coenzyme B12 and organocobaloximes toward DNA nucleotides was also examined in order to compare the reactivity with those of DNA cleavage. In contrast to the efficient DNA strand scission by photoirradiation of methylcobalamin and (DH)2(CH3)Co(py) in the absence of oxygen, the photoirradiation in the presence of oxygen under otherwise the same experimental conditions resulted in no DNA cleavage. This indicates that the DNA cleavage by alkyl radicals is suppressed by molecular oxygen, because alky radicals are converted to the much less reactive alkylperoxyl radicals.