Low-Coordinate Synthetic Models for Nitrogenase Activity

项目摘要 在固氮酶中，铁硫团簇通过执行电子转移位点，超越了它们通常的作用。 氮气的多电子还原为氨。因此，这种酶显示了铁硫惊人的催化潜力 生物系统中的团簇。除了其独特的还原氮气的能力外，FeMoco的活性中心 固氮酶具有碳化物(C4)，这是生物化学中的一个新特征。生物合成中的中间体 催化机理可能有氢化物、卡宾、氮气和肼，这些都是未知的 在其他酶中。了解固氮酶的结构和功能之间的关系是由 与FeMoco有特定相似性的合成分子。虽然它们被简化了，但它们做到了 可以一次测试一个结构特征，而不会出现其他辅因子和蛋白质的复杂情况。 我们的指导性假设是碳化物持有并释放低配位的铁，它可以形成Fe？N 2和 Fe-H中间体。在这个假说中，FeMoco中的硫化物施主给出了反应性的高自旋电子 配置。我们将使用合成铁簇和硫化物、氮化物、 卡宾和碳化物桥。具有这些特征的合成化合物将显示出建议的可行性 铁硫簇上的官能团，建立这些官能团的光谱特征，以及 展示他们的行为是否与FeMoco生物合成和机制的模型一致。 在这项拟议的研究中，我们将用每一种合成含铁化合物 以下新功能：不饱和铁硫团簇、硫化铁氢化物簇合物、高 自旋碳化铁和碳化物团簇，以及氮气裂解铁络合物。与世隔绝和 通过使用体积大的支撑基，这些化合物的表征成为可能。笨重的 基团还有助于结晶，并提高在可在低温下使用的溶剂中的溶解度。 将使用结晶学、动力学研究、电化学和反应性来阐明原子水平的细节 小分子结合和还原的基本步骤。合成的络合物将通过以下方式进行评估 Endor、红外、拉曼、穆斯堡尔和X射线吸收光谱，提供了 新模型化合物的结构和固氮酶的已知数据。 我们预计，拟议的工作将为固氮酶的反应途径带来有价值的先例。 尽管生物无机化学中的多电子氧化反应机理已为人们所熟知， 关于多电子生物还原的知识远远落后，特别需要 铁硫团簇的小分子反应研究。因此，从根本上讲， 了解固氮酶中的硫化铁簇如何结合和转化小分子，这些小分子对 生活。从长远来看，了解生物系统中小分子减少的机制也可能 导致了用于化学合成的新催化剂，产生了更广泛的影响。

Project Summary In nitrogenases, iron­sulfur clusters transcend their usual role as electron transfer sites, by performing the multielectron reduction of N2 to NH3. This enzyme thus shows the amazing catalytic potential of iron­sulfur clusters in biological systems. In addition to its unique ability to reduce N2, the FeMoco active site of nitrogenase has a carbide (C4­), a feature that is new in biological chemistry. Intermediates in the biosynthesis and catalytic mechanism are likely to have hydride, carbene, N2, and hydrazine moieties, which are unknown in other enzymes. Learning the relationship between the structure and function of nitrogenase is aided by synthetic molecules that have specific similarities to the FeMoco. Though they are simplified, they make it possible to test structural features one at a time without the complication of the other cofactors and protein. Our guiding hypothesis is that carbide holds and releases low­coordinate iron, which can form Fe­N2 and Fe­H intermediates. In this hypothesis, sulfide donors in the FeMoco give reactive high­spin electronic configurations. We will test these ideas using synthetic iron clusters with combinations of sulfide, nitride, carbene and carbide bridges. Synthetic compounds with these features will show the feasibility of the proposed functional groups on iron­sulfur clusters, establish the spectroscopic signatures of these functional groups, and show whether their behavior is consistent with the models for FeMoco biosynthesis and mechanism. In the proposed research, we will create synthetic iron­containing compounds with each of the following novel functionalities: unsaturated iron­sulfur clusters, iron­sulfide­hydride clusters, high­ spin iron­carbene and carbide clusters, and N2­cleaving iron complexes. The isolation and characterization of these compounds is made possible by the use of bulky supporting groups. The bulky groups also facilitate crystallization, and enhance solubility in solvents that can be used at low temperature. Crystallography, kinetic studies, electrochemistry, and reactivity will be used to elucidate the atomic­level detail of the elementary steps of small­molecule binding and reduction. The synthetic complexes will be evaluated by ENDOR, infrared, Raman, Mössbauer, and X­ray absorption spectroscopies to provide a link between the structures of novel model compounds and the known data for nitrogenases. We anticipate that the proposed work will lead to valuable precedents for reaction pathways in nitrogenases. Although much is known about the mechanisms of multielectron oxidation reactions in bioinorganic chemistry, the knowledge about multielectron biological reductions lags far behind, and there is particular need for research on small­molecule reactions of iron­sulfur clusters. Therefore, there is fundamental importance in learning how the iron­sulfide cluster in nitrogenase binds and transforms small molecules that are essential for life. In the long run, understanding the mechanisms of small­molecule reduction in biological systems may also lead to new catalysts for use in chemical synthesis, giving an even broader impact.