Lippard Stephen J
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Philos Trans A Math Phys Eng Sci. 2005 Apr 15;363(1829):861-77; discussion 1035-40. doi: 10.1098/rsta.2004.1532.
Nature uses carboxylate-bridged diiron centres at the active sites of enzymes that catalyse the selective hydroxylation of hydrocarbons to alcohols. The resting diiron(III) state of the hydroxylase component of soluble methane monooxygenase enzyme is converted by two-electron transfer from an NADH-requiring reductase into the active diiron(II) form, which subsequently reacts with O2 to generate a high-valent diiron(IV) oxo species (Q) that converts CH4 into CH3OH. In this step, C-H bond activation is achieved through a transition state having a linear C...H...O unit involving a bound methyl radical. Kinetic studies of the reaction of Q with substrates CH3X, where X=H, D, CH3, NO2, CN or OH, reveal two classes of reactivity depending upon whether binding to the enzyme or C-H bond activation is rate-limiting. Access of substrates to the carboxylate-bridged diiron active site in the hydroxylase (MMOH) occurs through a series of hydrophobic pockets. In the hydroxylase component of the closely related enzyme toluene/o-xylene monooxygenase (ToMOH), substrates enter through a wide channel in the alpha-subunit of the protein that tracks a course identical to that found in the structurally homologous MMOH. Synthetic models for the carboxylate-bridged diiron centres in MMOH and ToMOH have been prepared that reproduce the stoichiometry and key geometric and physical properties of the reduced and oxidized forms of the proteins. Reactions of the diiron(II) model complexes with dioxygen similarly generate reactive intermediates, including high-valent species capable not only of hydroxylating pendant C-H bonds but also of oxidizing phosphine and sulphide groups.
自然界在催化碳氢化合物选择性羟基化为醇类的酶的活性位点使用羧酸盐桥连的二铁中心。可溶性甲烷单加氧酶的羟化酶组分的静止二铁（III）状态通过来自需要NADH的还原酶的双电子转移转化为活性二铁（II）形式，其随后与O2反应生成将CH4转化为CH3OH的高价二铁（IV）氧代物种（Q）。在这一步中，C-H键活化是通过具有涉及结合甲基自由基的线性C...H...O单元的过渡态实现的。对Q与底物CH3X（其中X = H、D、CH3、NO2、CN或OH）反应的动力学研究揭示了两类反应性，这取决于与酶的结合或C-H键活化是否是限速步骤。底物通过一系列疏水口袋进入羟化酶（MMOH）中羧酸盐桥连的二铁活性位点。在与甲苯/邻二甲苯单加氧酶（ToMOH）密切相关的酶的羟化酶组分中，底物通过蛋白质α亚基中的一个宽通道进入，该通道的走向与结构同源的MMOH中发现的相同。已经制备了MMOH和ToMOH中羧酸盐桥连二铁中心的合成模型，这些模型再现了蛋白质还原和氧化形式的化学计量以及关键的几何和物理性质。二铁（II）模型配合物与双氧的反应同样会生成反应中间体, 包括不仅能够羟基化侧链C-H键，而且能够氧化膦和硫化物基团的高价物种。
