Bleomycin, metal-dioxygen complexes

The antitumor antibiotic bleomycin (BLM) is believed to cause cytotoxicity through its ability, in the combined presence of dioxygen and a metal ion cofactor (204), to bind to and degrade DNA (205). Iron complexes of BLM have aroused special attention, as such complexes are the first (vide supra concerning the discussion of hemerythrin and hemocyanin) non-heme-iron complexes with a significant capacity for dioxygen activation (206). 

Bleomycin is a clinically useful family of glycopeptide antibiotic congeners with antitumoral activity. Cytotoxicity results from oxidative DNA damage. Bleomycin and transition metal ions form complexes that react with dioxygen and oxidize DNA. DNA damage is due to an activated form of iron bleomycin which forms from Fe -bleomycin in the presence of dioxygen and a source of electrons or from Fe -bleomycin in the presence of H2O2. 

Time-resolved Raman spectroscopy has been utilized to detect v(Fe-0) in an early intermediate in the reduction of O2 by cytochrome oxidase. " Consideration of other data on dioxygen adducts indicates that this species is most likely the cytochrome al -02 complex. The i/(Fe -02) frequency is elevated relative to that observed for other systems from which it may be concluded that at 10 /jls into the oxidase reaction the 0=0 bond is weakened. The ligand, HAPH (1) (R = H, R = 4-imidazolyl), has been been employed as a model for the metal binding site of Bleomycin [Fe(II)(HAPH)] and [Fe(BLM)] were subjected to oxida-... 

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