Fe(II) Complexes That Mimic the Active Site Structure of Acetylacetone Dioxygenase: O₂ and NO Reactivity

Abstract

Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the dioxygen-dependent degradation of β-dicarbonyl compounds. The Dke1 active site contains a nonheme monoiron(II) center facially ligated by three histidine residues (the 3His triad); coordination of the substrate in a bidentate manner provides a five-coordinate site for O2 binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme-substrate intermediate of Dke1 (Park, H.; Baus, J.S.; Lindeman, S.V.; Fiedler, A.T. Inorg. Chem. 2011, 50, 11978–11989). The 3His triad was modeled with three different facially coordinating N3 supporting ligands, and substituted β-diketonates (acacX) with varying steric and electronic properties were employed. Here, we describe the reactivity of our Dke1 models toward O2 and its surrogate nitric oxide (NO), and report the synthesis of three new Fe(II) complexes featuring the anions of dialkyl malonates. Exposure of [Fe(Me2Tp)(acacX)] complexes (where R2Tp = hydrotris(pyrazol-1-yl)borate with R-groups at the 3- and 5-positions of the pyrazole rings) to O2 at −70 °C in toluene results in irreversible formation of green chromophores (λmax ~750 nm) that decay at temperatures above −60 °C. Spectroscopic and computational analyses suggest that these intermediates contain a diiron(III) unit bridged by a trans µ-1,2-peroxo ligand. The green chromophore is not observed with analogous complexes featuring Ph2Tp and PhTIP ligands (where PhTIP = tris(2-phenylimidazoly-4-yl)phosphine), since the steric bulk of the phenyl substituents prevents formation of dinuclear species. While these complexes are largely inert toward O2, Ph2Tp-based complexes with dialkyl malonate anions exhibit dioxygenase activity and thus serve as functional Dke1 models. The Fe/acacX complexes all react readily with NO to yield highspin (S = 3/2) {FeNO}7 adducts that were characterized with crystallographic, spectroscopic, and computational methods. Collectively, the results presented here enhance our understanding of the chemical factors involved in the oxidation of aliphatic substrates by nonheme iron dioxygenases.

Transition Metal Complexes and the Activation of Dioxygen

“…A similar intermediate was proposed in studies of an Fe(II)-acetylacetone model of β-diketone dioxygenase [190]. Indirect evidence for the intermediacy of an iron(II)-superoxo complex was also cited in studies of 52 ( Figure 27), which reacted with O 2 only in the presence of reductant and proton donors [191] or substrates with weak C-H bonds [192] to yield iron(III)-hydroperoxo or iron(IV)-oxo species.…”

Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective

“…28–29 The formation of a dimeric peroxo-bridged structure from the reaction of monomeric Fe II complex + O 2 was demonstrated in a separate study utilizing hydrotris-(pyrazol-1-yl)borate-bound iron(II)–diketonate complex. 97 …”

Utilizing the Trispyrazolyl Borate Ligand for the Mimicking of O2-Activating Mononuclear Nonheme Iron Enzymes

“…Within the Tp Ph2 Fe-(acac X ) series, it thus appeared that O 2 reactivity was primarily governed by the relative energies of acac x π-electrons, not the Fe redox potentials. 37 Concluding, it was confirmed that only activated, electronrich substrate ligands (malonates) can be cleaved in model systems for the Dke1 in the absence of supporting secondary interactions. 4.…”

“…37 When the reactions were carried out in acetonitrile as the solvent (with trace amounts of water), some [Tp Me2 Fe(acac x )] complexes finally yielded in trinuclear compounds with bridging carboxylate, oxido, and hydroxido ligands, related to 16. 33 Unlike the [Tp Me2 Fe(acac x )] series, complexes with Tp Ph2 or TlP ligands exhibited a significantly lower reactivity upon exposure to O 2 .…”