THE SECONDARY AMINE GROUP OF BLEOMYCIN IS NOT INVOLVED IN INTRAMOLECULAR HYDROGEN-BONDING IN ACTIVATED BLEOMYCIN

The iron complexes of two designed ligands, PMAH and PMCH, that mimic the metal-chelating portion of the antitumor drug bleomycin (BLM) reac t with dioxygen to afford low-spin hydroperoxo-Fe(III) species that ex hibit EPR spectra very similar to that of the ''activated bleomycin''. Much like the Fe-BLMs, these active intermediates induce DNA damage v ia an oxidative pathway and also promote facile oxo transfer to olefin ic substrates. A recent theoretical study concluded that activation of Fe-BLM might involve internal hydrogen bonding between the secondary NH group and the coordinated hydroperoxo unit. This work demonstrates that the O2-activation capacity of the iron complex of PMCH, a ligand that contains a N-CH3 group instead of the N-H group of PMAH, is ident ical to that of the iron complex of PMAH. It is, therefore, evident th at the secondary amine group of PMAH (and BLM) does not assist the pro cess of O2 activation by forming an internal hydrogen bond.