Characterization of an Fe-III-OOH species and its decomposition product in a bleomycin model system

To model the mononuclear Fe-III-OOH species identified in the catalytic cycle of the anticancer drug bleomycin, the iron chemistry of the pentadentate ligand N-[bis(2-pyridylmethyl)aminoethyl]pyridine-2-carboxamide (H-PaPy3) has been investigated. The complex [Fe-III(PaPy3)OCH3](ClO4) was reacted with H2O2 to form a red species (lambda(max)=480 nm, epsilon=1800 M-1 cm(-1)) with an S=1/2 EPR signal at g=2.25, 2.17, and 1.95. This species has been identified by electrospray ionization mass spectrometry as [Fe-III(PaPy3)OOH](ClO4) and further characterized by resonance Raman and EXAFS analysis. The decomposition of this intermediate leads to the modification of the ligand, as revealed by H-1 NMR. One hydrogen atom is substituted by a solvent-derived methoxy group. The substitution at this site is a result of the two-electron oxidation of the ligand following the heterolytic cleavage of the O-O bond of the Fe-III-OOH species. This is a plausible mechanism to rationalize related ligand modifications that have been proposed in the decay of activated bleomycin.