Ferric Bleomycin Catalyzed Reduction of 10-hydroperoxy-8,12-octadecadienoic Acid: Evidence For Homolytic 0–0 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 0–0 bond. Product 4 results from heterolysis of the peroxy 0–0 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 0–0 bond of 1 almost exclusively while supporting various oxidative reactions.