Mechanism of bleomycin suicide: a Car-Parrinello molecular dynamics investigation.

Using first-principles molecular dynamics simulations (Car-Parrinello method) we investigated the possible reaction pathways for decay of the active bleomycin-Fe(III)-OOH complex, so-called bleomycin suicide. The theoretical model of activated bleomycin contains the whole metal bonding domain of the bleomycin ligand. Simulations performed both in a vacuum and in water show that a facile decaying process involves a homolytic O-O bond cleavage with an almost simultaneous hydrogen atom abstraction. The formation of an intra- or intermolecular hydrogen bond appears to be crucial for the decay of the activated bleomycin. We did not observe any evidence of heterolytic cleavage of the O-O bond of the Fe(III)-OOH species.