RESUMO
The antitumor drug bleomycin (BLM) is proposed to act via a low-spin iron(III) hydroperoxide intermediate called "activated bleomycin". To gain more insight into the mechanistic aspects of catalytic oxidation by these intermediates we have studied the reactivity of [(N4Py)Fe(CH3CN)](ClO4)2 (1) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) with excess H2O2. Under these conditions a transient purple species is generated, [(N4Py)FeOOH]2- (2), which has spectroscopic features and reactivity strongly reminiscent of activated bleomycin. The catalytic oxidation of alkanes such as cyclohexane, cyclooctane, and adamantane by 1 with H2O2 gave the corresponding alcohols and ketones in up to 31% yield. It was concluded, from the O2 sensitivity of the oxidation reactions, the formation of brominated products in the presence of methylene bromide, and the nonstereospecificity of the oxidation of cis- or trans-dimethylcyclohexane, that long-lived alkyl radicals were formed during the oxidations. Oxidation of alkenes did not afford the corresponding epoxides in good yields but resulted instead in allylic oxidation products in the case of cyclohexene, and cleavage of the double bond in the case of styrene. Addition of hydroxyl radical traps, such as benzene and acetone, led to only partial quenching of the reactivity. The kinetic isotope effects for cyclohexanol formation, ranging from 1.5 in acetonitrile to 2.7 in acetone with slow addition of H2O2, suggested the involvement of a more selective oxidizing species in addition to hydroxyl radicals. Monitoring the UV/Vis absorption of 2 during the catalytic reaction showed that 2 was the precursor for the active species. On the basis of these results it is proposed that 2 reacts through homolysis of the O-O bond to afford two reactive radical species: [(N4Py)Fe(IV)O]2+ and *OH. The comparable reactivity of 1 and Fe-BLM raises the possibility that they react through similar mechanistic pathways.
