Catalytic Oxidation with a Non-Heme Iron Complex That Generates a Low-Spin FeIIIOOH Intermediate

Abstract

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.

End-On and Side-On Peroxo Derivatives of Non-Heme Iron Complexes with Pentadentate Ligands: Models for Putative Intermediates in Biological Iron/Dioxygen Chemistry

“…Examination of the reactivity of 1b toward organic substrates has shown that this form is relatively inert compared to its conjugate acid. 38,71 A similar inertness has been noted for [Fe(EDTA)(η 2 -O 2 )] 3-. 39 A sideon peroxoiron(III) species has been postulated in the mechanism of arene cis-dihydroxylation by the Rieske dioxygenases 4, 74 and recently observed in the crystal structure of a ternary enzyme-substrate-O 2 complex of naphthalene dioxygenase.…”

“…In line with DFT calculations, [35][36][37] the low-spin iron(III) center plays a role in weakening the O-O bond and priming it for homolysis prior to substrate attack, a reactivity documented for 1a. 71 Comparison of 1a with activated bleomycin reveals major spectroscopic differences between the two complexes. First of all, the quadrupole splittings of both complexes (Table 2) differ substantially, and analysis of the g values with the Griffith model indicates that ∆/λ ≈ 12 for 1a compared to ∆/λ ≈ 8.74 20 for activated bleomycin.…”

Hydrocarbon Oxidation with H2O2, Catalyzed by Iron Complexes with a Polydentate Pyridine-Based Ligand

“…2, whereas more selective oxidants give substantially higher values. For example, values of 3.1-3.3 for [Fe(N4py)(CH 3 CN)](ClO 4 ) 2 were observed [15]. The relatively low C3/C2 ratio observed for catalyst 1 implies that the present catalytic reactions are distinct from a Fenton type free-radical oxidation reaction for which the typical C3/C2 ratios are higher than 20 [25].…”

“…Others include iron(II) complexes containing pyridine-based pentadentate ligands, with two to five pyridine rings [9][10][11][12][13][14][15][16]. These complexes can react with H 2 O 2 , forming metastable Fe-OOH intermediates, and in some cases to catalyze alkane hydroxylation [11,15].…”

Iron-catalysed oxidation and halogenation of organic matter in nature

“…[84,101] The very high Fe IV/III redox potentials [123,124] suggest that the bispidine-based ferryl complexes should even be able to oxidise the strong C-H bonds of alkanes. [89,124] With bispidines and several other ligand systems, [125][126][127] various possible high-valent iron species were proposed to be responsible for substrate activation, i.e. Fe V ¼O (heterolytic O-O cleavage in the Fe III -OOH intermediate), Fe IV ¼O together with OH radicals (homolytic O-O cleavage in the Fe III precursor) or the products of direct oxidation of the Fe II precursor to the catalytically active Fe IV oxidant (see above).…”