Mechanism of DNA cleavage by cationic manganese porphyrins: hydroxylations at the 1'-carbon and 5'-carbon atoms of deoxyriboses as initial damages.

Cationic manganese-porphyrin complexes, free or targetted with an intercalating agent, are able to cleave DNA using oxygen atom donors like potassium monopersulfate or magnesium monoperphthalate as coreactants. Detailed studies of the cleavage of calf thymus DNA, before and after a heating step, show that free bases and 5-methylene-2-furanone are the main reaction products, indicating that hydroxylation at the 1'-carbon atom is the main target of these chemical agents. These data confirm that metalloporphyrin derivatives interact with the minor groove of double-stranded DNA. Hydroxylation of one of the two C-H bonds at position-5' is another initial DNA damage, characterized by the formation of furfural as sugar degradation product. Besides these two main initial damage sites, a low contribution of a hydroxylation reaction at C4' can not be definitively discounted, while an hydroperoxidation route at C4' can be excluded.