Inserting carbide in ligand templated iron-sulfur clusters and their reactivity towards hydrides and N2

项目摘要 固氮酶通过催化还原N2产生NH3来提供几乎所有的生物可利用氮。活性 N2还原位点是铁-钼辅因子（MoFe 7S 9 C或FeMoco），其特征在于高自旋铁中心 由硫化物（S2−）和一种有趣的碳化物（C4−）桥接，桥接六个铁中心。从生物学上讲， 前所未有的碳化物配体提出了关于其插入FeMoco的机制的问题。碳化物 来源于通过S-腺苷甲硫氨酸（SAM）酶转移到铁-硫簇的甲基。 然而，将这种甲基转化为最终间隙碳化物的机制，以及中间体， 沿着道路，仍然未知。自然系统将这种碳化物插入固氮酶的事实也导致了 碳化物对FeMoco反应性的结构和电子影响的问题。 这个提议的主要目的是研究铁硫簇合物中的碳化物插入，以了解铁硫簇合物中的碳化物是什么。 化学上可行的中间体可能与FeMoco的生物合成有关。在研究 FeMoco的生物合成在天然酶中是困难的，模型簇为我们提供了对特异性FeMoco的合成控制。 结构和电子因素来系统地测试我们的假设。我们的主要战略是设计和 合成可以模板化仅具有硫供体的三核铁簇的支架配体。硫 供体将产生高自旋的配位不饱和铁位点，其模拟铁的配位环境， 费莫科我们建议在铁-乙炔中安装甲基（CH 3）、卡宾（CH 2）、碳炔（CH）和碳化物（C）配体。 硫簇，并研究这些化合物之间的相互转化。这些物种被认为 FeMoco生物合成过程中的中间体，这些簇之间的相互转化将告诉我们， 在FeMoco的生物合成过程中，哪些化学转化是可行的。 最后，我们的目标是探索N2绑定的铁硫簇。我们建议，这些最好是从 桥连铁硫簇，在仿生机制，这将有助于阐明的能力，H2 消除以实现N2结合。我们将在这些仿生簇上安装氢化物配体， 还原消除H2以使N2结合。该过程模拟了N2还原过程中的E4中间体， 费莫科这些研究将推进我们对关键中间体和机制的基本理解 在FeMoco中的N2还原期间。 我在荷兰集团的培训将扩大我的技术研究能力，导师，和批判性写作 和演讲技巧。耶鲁大学的领先的生物无机和合成无机化学家的集合，使它成为一个 获得生物无机化学、配体设计和合成以及机械研究技能的理想环境。

PROJECT SUMMARY Nitrogenases provide nearly all bioavailable nitrogen by catalytically reducing N2 to produce NH3. The active site for N2 reduction is an iron-molybdenum cofactor (MoFe7S9C, or FeMoco) that features high-spin iron centers bridged by sulfide (S2−) and an intriguing carbide (C4−) that bridges six iron centers. This biologically unprecedented carbide ligand raises questions concerning its mechanism of insertion into FeMoco. The carbide originates from a methyl group transferred to an iron-sulfur cluster by a S-adenosylmethionine (SAM) enzyme. However, the mechanisms that convert this methyl group into the final interstitial carbide, and the intermediates along the way, remain unknown. The fact that natural systems insert this carbide into nitrogenases also leads to questions about the structural and electronic impact of carbide on the reactivity of FeMoco. A primary aim of this proposal is to study carbide insertion in iron-sulfur clusters to understand what chemically feasible intermediates may be relevant to the biosynthesis of FeMoco. While studying the biosynthesis of FeMoco is difficult in the native enzyme, model clusters provide us synthetic control over specific structural and electronic factors to systematically test our hypotheses. Our main strategy is to design and synthesize scaffold ligands that can template trinuclear iron clusters featuring only sulfur donors. The sulfur donors will yield high-spin, coordinately unsaturated iron sites that mimic iron's coordination environment in FeMoco. We propose to install methyl (CH3), carbene (CH2), carbyne (CH), and carbide (C) ligands in the iron- sulfur clusters and study the interconversion between these compounds. These species are proposed intermediates during the biosynthesis of FeMoco, and the interconversion between these clusters will inform us what chemical transformations are feasible during the biosynthesis of FeMoco. Finally, we aim to explore N2 binding by iron-sulfur clusters. We propose that these are best accessed from hydride-bridged iron-sulfur clusters, in a biomimetic mechanism that will help to elucidate the ability of H2 elimination for enabling N2 binding. We will install hydride ligands on these biomimetic clusters and exploit reductive elimination of H2 to enable N2 binding. This process mimics the E4 intermediate during N2 reduction by FeMoco. These studies will advance our fundamental understanding of key intermediates and mechanisms during N2 reduction in FeMoco. My training in the Holland group will expand my technical research aptitudes, mentorship, and critical writing and presentation skills. Yale's collection of leading bioinorganic and synthetic inorganic chemists renders it an ideal setting for gaining skills in bioinorganic chemistry, ligand design and synthesis, and mechanistic studies.