Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Am Chem Soc. 2011 Oct 19;133(41):16657-67. doi: 10.1021/ja207131g. Epub 2011 Sep 21.
An [Fe(IV)(2)(μ-O)(2)] diamond core structure has been postulated for intermediate Q of soluble methane monooxygenase (sMMO-Q), the oxidant responsible for cleaving the strong C-H bond of methane and its hydroxylation. By extension, analogous species may be involved in the mechanisms of related diiron hydroxylases and desaturases. Because of the paucity of well-defined synthetic examples, there are few, if any, mechanistic studies on the oxidation of hydrocarbon substrates by complexes with high-valent [Fe(2)(μ-O)(2)] cores. We report here that water or alcohol substrates can activate synthetic [Fe(III)Fe(IV)(μ-O)(2)] complexes supported by tetradentate tris(pyridyl-2-methyl)amine ligands (1 and 2) by several orders of magnitude for C-H bond oxidation. On the basis of detailed kinetic studies, it is postulated that the activation results from Lewis base attack on the [Fe(III)Fe(IV)(μ-O)(2)] core, resulting in the formation of a more reactive species with a [X-Fe(III)-O-Fe(IV)═O] ring-opened structure (1-X, 2-X, X = OH(-) or OR(-)). Treatment of 2 with methoxide at -80 °C forms the 2-methoxide adduct in high yield, which is characterized by an S = 1/2 EPR signal indicative of an antiferromagnetically coupled [S = 5/2 Fe(III)/S = 2 Fe(IV)] pair. Even at this low temperature, the complex undergoes facile intramolecular C-H bond cleavage to generate formaldehyde, showing that the terminal high-spin Fe(IV)═O unit is capable of oxidizing a C-H bond as strong as 96 kcal mol(-1). This intramolecular oxidation of the methoxide ligand can in fact be competitive with intermolecular oxidation of triphenylmethane, which has a much weaker C-H bond (D(C-H) 81 kcal mol(-1)). The activation of the [Fe(III)Fe(IV)(μ-O)(2)] core is dramatically illustrated by the oxidation of 9,10-dihydroanthracene by 2-methoxide, which has a second-order rate constant that is 3.6 × 10(7)-fold larger than that for the parent diamond core complex 2. These observations provide strong support for the DFT-based notion that an S = 2 Fe(IV)═O unit is much more reactive at H-atom abstraction than its S = 1 counterpart and suggest that core isomerization could be a viable strategy for the [Fe(IV)(2)(μ-O)(2)] diamond core of sMMO-Q to selectively attack the strong C-H bond of methane in the presence of weaker C-H bonds of amino acid residues that define the diiron active site pocket.
一种[Fe(IV)(2)(μ-O)(2)]金刚石核结构被假定为可溶性甲烷单加氧酶（sMMO-Q）的中间 Q，该氧化剂负责断裂甲烷的强 C-H 键及其羟化。通过扩展，类似的物质可能参与相关二铁羟化酶和去饱和酶的机制。由于定义明确的合成实例很少，如果有的话，那么对于具有高价[Fe(2)(μ-O)(2)]核的配合物氧化烃底物的机制研究就很少。我们在这里报告说，水或醇底物可以通过配位四面体三（吡啶-2-甲基）胺配体（1 和 2）支持的合成[Fe(III)Fe(IV)(μ-O)(2)]配合物，将 C-H 键氧化的级数提高几个数量级。基于详细的动力学研究，推测这种激活是由于路易斯碱对[Fe(III)Fe(IV)(μ-O)(2)]核的攻击，导致形成具有[X-Fe(III)-O-Fe(IV)═O]开环结构的更具反应性的物质（1-X、2-X，X = OH(-)或 OR(-)）。在-80°C 下用甲氧基处理 2 可高产率地形成 2-甲氧基加合物，其特征在于 S = 1/2 EPR 信号，表明反铁磁耦合[S = 5/2 Fe(III)/S = 2 Fe(IV)]对。即使在如此低的温度下，该配合物也能轻易地进行分子内 C-H 键断裂，生成甲醛，表明末端高自旋 Fe(IV)═O 单元能够氧化强至 96 kcal mol(-1)的 C-H 键。这种甲氧基配体的分子内氧化实际上可以与三苯甲烷的分子间氧化竞争，三苯甲烷的 C-H 键较弱（D(C-H) 81 kcal mol(-1)）。通过 2-甲氧基氧化 9,10-二氢蒽，强烈说明了[Fe(III)Fe(IV)(μ-O)(2)]核的激活，其二级速率常数比母体金刚石核配合物 2 大 3.6×10(7)倍。这些观察结果为基于 DFT 的观点提供了有力支持，即 S = 2 Fe(IV)═O 单元在 H 原子的夺取方面比其 S = 1 对应物更具反应性，并表明核异构化可能是 sMMO-Q 的[Fe(IV)(2)(μ-O)(2)]金刚石核选择性攻击甲烷强 C-H 键的可行策略存在定义二铁活性位点口袋的氨基酸残基较弱的 C-H 键。
