title: Mechanism of bleomycin suicide: a Car-Parrinello molecular dynamics investigation.
abstract: 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.
authors.affiliation: Gorlaeus Laboratories, Leiden Institute of Chemistry, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Karawajczyk
authors.forename: Christian
authors.initials: C
authors.lastname: Gossens
authors.forename: Ursula
authors.initials: U
authors.lastname: Roethlisberger
authors.forename: Francesco
authors.initials: F
authors.lastname: Buda
mesh_terms: D001761:Bleomycin / Q000737:chemistry*; D003198:Computer Simulation; D005290:Ferric Compounds / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular
chemical_list: D005290:Ferric Compounds; D008024:Ligands; D001761:Bleomycin