Low-Coordinate Synthetic Models for Nitrogenase Activity

细菌固氮酶催化N/2还原（“固定”）为氨，这是一个令人惊讶的过程。 一种将前体转化为所有含氮生物分子的过程。由于固氮酶是多电子还原的终极过程，因此发现固氮酶的详细机制是生物化学中的一个重大挑战。N2还原发生在称为FeMoco的金属簇上。在添加电子和质子后，FeMoco以某种方式结合，断裂并将N2质子化为NH 4 *。FeMoco附近的突变表明，N2和其他底物结合在簇的富铁中心附近。基于文献晶体学，光谱学和固氮酶的机制研究，我们制定了一个合理的铁基还原和N2结合的机制。这种机制，基于低配位铁，作为我们的指导假设。关键的中间体含有只有3或4个连接的铁，其他的具有Fe-H键。然而，文献中很少有合成的3-配位铁化合物，也没有配位数为4或更少的Fe-H配合物。 该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，N2结合，N2反应和裂解，以及N-H键的形成。由于孤立的Fe-H复合物完全打破多重键，它们将被研究作为固氮酶中间体的反应模型。具有约束几何形状的多金属络合物将显示最有利于N2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，如在假设的FeMoco机制。这些研究将阐明低配位铁化学的基本原理，这对于理解FeMoco和大型合成簇的工作是必要的。

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.