Ferric bleomycin catalyzed reduction of 10-hydroperoxy-8,12-octadecadienoic acid: evidence for homolytic O-O bond scission.
10-Hydroperoxy-8,12-octadecadienoic acid (1) is reduced by ferric bleomycin in aqueous and methanol solutions to yield 10-oxo-8-decenoic acid (2) as the major product (80-90%). Trace amounts of 10-oxo-8,12-octadecadienoic acid (3) (5-10%) and 10-hydroxy-8,12-octadecadienoic acid (4) (5-10%) were also detected. The reduction product ratios remained relatively constant in the presence or absence of the reducing substrate phenol, over the pH range 6.5-8.5, in incubations from 30 s to 1 h, and over a series of ferric drug concentrations. In the presence of phenol, incubations of ferric bleomycin and 1 yielded 2,2'-biphenol and 4,4'-biphenol as oxidation products. In reactions where phenol was replaced with the drug's biological substrate DNA, 1 was found to support ferric bleomycin mediated DNA degradation. Extracts from these assays also found 2 to be the major reduction product derived from the oxidant, with trace quantities of 3 and 4 present. Control experiments demonstrated the reactions to be dependent on both 1 and ferric bleomycin. The reduction products 2 and 3 have previously been shown to originate from transient alkoxyl radicals formed by homolysis of the peroxy O-O bond. Product 4 results from heterolysis of the peroxy O-O bond [Labeque, R., & Marnett, L. J. (1987) J. Am. Chem. Soc. 109, 2828-2829]. The results of this investigation indicate that ferric bleomycin catalyzes the homolytic cleavage of the O-O bond of 1 almost exclusively while supporting various oxidative reactions.
Padbury
G
G
Department of Biochemistry, University of Illinois, Urbana 61801.
Sligar
S G
SG
Labeque
R
R
Marnett
L J
LJ
D001665:Binding Sites; D001761:Bleomycin / Q000494:pharmacology / Q000031:analogs & derivatives; D004247:DNA / Q000378:metabolism; D066298:In Vitro Techniques; D008041:Linoleic Acids; D010084:Oxidation-Reduction; D019800:Phenol; D010636:Phenols
D008041:Linoleic Acids; D010636:Phenols; C023503:iron bleomycin; D001761:Bleomycin; D019800:Phenol; D004247:DNA; C058335:10-hydroperoxy-8,12-octadecadienoic acid