Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53201-1881, USA.
Inorg Chem. 2012 Oct 1;51(19):10279-89. doi: 10.1021/ic3012712. Epub 2012 Sep 13.
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-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 (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 (λ(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 μ-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.
乙酰丙酮双加氧酶(Dke1)是一种细菌酶,能催化β-二羰基化合物的双氧依赖降解。Dke1 的活性部位含有一个非血红素单核铁(II)中心,由三个组氨酸残基(3His 三联体)配位;底物以双齿配位方式提供五配位位点以结合 O2。最近,我们发表了一系列亚铁β-二酮配合物的合成和表征,这些配合物忠实地模拟了 Dke1 的酶-底物中间体(Park,H.;Baus,J.S.;Lindeman,S.V.;Fiedler,A.T. Inorg. Chem.2011,50,11978-11989)。3His 三联体由三个不同的面配位 N3 支撑配体模拟,并用具有不同空间位阻和电子性质的取代β-二酮(acac(X))。在此,我们描述了我们的 Dke1 模型对 O2 和其替代物一氧化氮(NO)的反应性,并报告了三种具有二烷基丙二酸根阴离子的新型 Fe(II)配合物的合成。在 -70°C 的甲苯中,将 [Fe((Me2)Tp)(acac(X))] 配合物(其中 (R2)Tp = 氢三(吡唑-1-基)硼酸,吡唑环的 3-和 5-位有 R-基团)暴露于 O2 下,会不可逆地形成绿色发色团(λ(max)∼750nm),这些发色团在温度高于-60°C 时会衰减。光谱和计算分析表明,这些中间体含有通过反式μ-1,2-过氧桥联的二铁(III)单元。用具有 (Ph2)Tp 和 (Ph)TIP 配体(其中 (Ph)TIP = 三(2-苯基咪唑-4-基)膦)的类似配合物则观察不到绿色色团,因为苯基取代基的空间位阻阻止了双核物种的形成。虽然这些配合物对 O2 基本没有反应,但具有二烷基丙二酸根阴离子的 (Ph2)Tp 基配合物表现出双加氧酶活性,因此可用作功能性 Dke1 模型。Fe/acac(X) 配合物均与 NO 快速反应,生成高自旋(S = 3/2){FeNO}(7)加合物,并用晶体学、光谱学和计算方法进行了表征。总的来说,这里呈现的结果增强了我们对非血红素铁双加氧酶氧化脂肪族底物所涉及的化学因素的理解。