Low-Coordinate Synthetic Models for Nitrogenase Activity

细菌固氮酶催化N/2还原(固定)为氨，这是一个令人惊叹的 形成所有含氮生物分子的前驱物质的过程。由于固氮酶是最终的多电子还原，因此对固氮酶的详细机理的发现在生物化学中是一个巨大的挑战。氮气还原发生在一种名为FeMoco的金属团簇上。在添加电子和质子后，FeMoco以某种方式结合、断裂并质子化N_2到NH_4*。FeMoco附近的突变表明，N2和其他底物在富铁的团簇中心附近结合。基于文献对固氮酶的结晶学、光谱和机理的研究，我们制定了一个合理的铁基还原和氮气结合机理。这种基于低配位铁的机制是我们的指导性假说。关键中间体中的铁只有3或4个键，其他的则有Fe-H键。然而，文献中很少有合成的三配位铁化合物，也没有配位数在四个或更少的铁-氢配合物。 本提案描述了合成低配位铁化合物的系统研究： 它们的性质、光谱特征、对固氮酶底物的反应性以及 典型的反应模式。选择实验来解决假设机制的几个步骤，包括还原活化、氮气结合、氮气反应和裂解以及N-H键的形成。由于孤立的Fe-H络合物完全断裂多个键，它们将作为固氮酶中间体的反应模型进行研究。几何构型受限的多金属络合物将显示出最有利于N_2裂解的排列。对关键反应的机理研究将澄清铁原子的允许和禁止反应，就像假设的FeMoco机理中的反应一样。这些研究将阐明低配位铁化学的基本原理，这是理解FeMoco和大型合成团簇的工作原理所必需的。

Bacterial nitrogenases catalyze the reduction ("fixation") of N/2 to ammonia, an amazing process that gives the precursor to all nitrogen-containing biomolecules. Because it is the ultimate multielectron reduction, discovery of the detailed mechanism of nitrogenase is a great challenge in biochemistry. N2 reduction occurs at a metal cluster called the FeMoco. After addition of electrons and protons, the FeMoco somehow binds, breaks, and protonates N2 to NH4*. Mutations near the FeMoco show that N2 and other substrates bind near the iron-rich center of the cluster. Based on literature crystallographic, spectroscopic, and mechanistic studies on nitrogenase, we have formulated a reasonable iron-based mechanism for reduction and N2 binding. This mechanism, based on low-coordinate iron, serves as our guiding hypothesis. Key intermediates have iron with only 3 or 4 attachments, and others with Fe-H bonds. However, the literature has few synthetic 3-coordinate iron compounds, and no Fe-H complexes with a coordination number of four or less. This proposal describes the systematic study of synthetic low-coordinate iron compounds: their properties, spectroscopic signatures, reactivity toward nitrogenase substrates, and characteristic reaction patterns. Experiments are chosen to address several steps of the hypothetical mechanism, including reductive activation, N2 binding, N2 reactions and cleavage, and N-H bond formation. Because isolated Fe-H complexes completely break multiple bonds, they will be studied as reactivity models for nitrogenase intermediates. Multimetallic complexes with constrained geometry will show the arrangement most conducive to N2 cleavage. Mechanistic studies on key reactions will clarify allowed and forbidden reactions of iron atoms like those in the hypotheticaL FeMoco mechanism. These studies will elucidate the fundamentals of low-coordinate iron chemistry, which is necessary to understand the workings of the FeMoco and large synthetic clusters.