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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 ?-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 O(2) binding. Recently, we published the synthesis and characterization of a series of ferrous ?-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 ?-diketonates (acac(X)) with varying steric and electronic properties were employed. Here, we describe the reactivity of our Dke1 models toward O(2) 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((Me2)Tp)(acac(X))] complexes (where (R2)Tp = hydrotris(pyrazol-1-yl)borate with R-groups at the 3- and 5-positions of the pyrazole rings) to O(2) at -70 °C in toluene results in irreversible formation of green chromophores (?(max) ?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 ?-1,2-peroxo ligand. The green chromophore is not observed with analogous complexes featuring (Ph2)Tp and (Ph)TIP ligands (where (Ph)TIP = 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 O(2), (Ph2)Tp-based complexes with dialkyl malonate anions exhibit dioxygenase activity and thus serve as functional Dke1 models. The Fe/acac(X) complexes all react readily with NO to yield high-spin (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.

SUBMITTER: Park H

PROVIDER: S-EPMC3965333 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Fe(II) complexes that mimic the active site structure of acetylacetone dioxygenase: O2 and NO reactivity.

Park Heaweon H Bittner Michael M MM Baus Jacob S JS Lindeman Sergey V SV Fiedler Adam T AT

Inorganic chemistry 20120913 19

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 O(2) binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme-substr ...[more]

PMID: 22974346

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Project description:Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

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Fe(II) complexes that mimic the active site structure of acetylacetone dioxygenase: O2 and NO reactivity.

Publications

Fe(II) complexes that mimic the active site structure of acetylacetone dioxygenase: O2 and NO reactivity.

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