title: Characterization of an Fe III-OOH species and its decomposition product in a bleomycin model system.
abstract: 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-PaPy(3)) has been investigated. The complex [Fe(III)(PaPy(3))OCH(3)](ClO(4)) was reacted with H(2)O(2) 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)(PaPy(3))OOH](ClO(4)) and further characterized by resonance Raman and EXAFS analysis. The decomposition of this intermediate leads to the modification of the ligand, as revealed by (1)H 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.
authors.affiliation: Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bukowski
authors.forename: Shourong
authors.initials: S
authors.lastname: Zhu
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Koehntop
authors.forename: William W
authors.initials: WW
authors.lastname: Brennessel
authors.forename: Lawrence
authors.initials: L
authors.lastname: Que
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001761:Bleomycin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000577:Amides; D000903:Antibiotics, Antineoplastic; D005290:Ferric Compounds; C431605:N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide; D011725:Pyridines; D001761:Bleomycin; C021024:ferric hydroxide; D006861:Hydrogen Peroxide