Low-Coordinate Synthetic Models for Nitrogenase Activity

描述（由申请人提供）：在固氮酶中，铁硫簇通过进行N2到NH3的多电子还原而超越了它们作为电子转移位点的通常作用。因此，这种酶显示了铁硫簇在生物学中的惊人催化潜力。 系统.除了其独特的还原N2的能力之外，固氮酶的FeMoco活性位点具有碳化物（C4-），这是生物化学中的新特征。在生物合成和催化机制的中间体可能有氢化物，卡宾，N2和肼部分，这是未知的其他酶。了解固氮酶的结构和功能之间的关系是通过与FeMoco具有特定相似性的合成分子来帮助的。虽然它们是简化的，但它们使测试结构成为可能。 特征在于一次一个，而没有其他辅因子和蛋白质的复杂化。我们的指导假设是，碳化物持有和释放低配位铁，可以形成Fe-N2和Fe-H中间体。在这个假设中，FeMoco中的硫化物供体给出反应性高自旋电子构型。我们将使用硫化物、氮化物、卡宾和碳化物桥的合成铁簇来测试这些想法。具有这些特征的合成化合物将显示所提出的铁硫簇合物上的官能团的可行性， 建立这些官能团的光谱特征，并显示它们的行为是否与FeMoco生物合成和机制的模型一致。在拟议的研究中，我们将创建具有以下每一种新功能的合成含铁化合物：不饱和铁-硫簇合物、铁-硫化物-氢化物簇合物、高自旋铁-卡宾和碳化物簇合物以及N2-裂解铁络合物。这些化合物的分离和表征通过使用大体积的支持基团而成为可能。大体积基团还促进结晶，并增强在可在低温下使用的溶剂中的溶解度。晶体学，动力学研究，电化学和反应性将被用来阐明小分子结合和还原的基本步骤的原子级细节。将通过ENDOR、红外、拉曼、穆斯堡尔和X射线吸收光谱对合成的复合物进行评价，以提供新型模型化合物的结构与固氮酶的已知数据之间的联系。我们预计，拟议的工作将导致有价值的先例固氮酶的反应途径。虽然在生物无机化学中对多电子氧化反应的机理已经有了很多的了解，但对多电子生物还原反应的认识还远远落后，特别是对铁硫簇合物小分子反应的研究还很有必要。因此，了解固氮酶中的硫化铁簇如何结合和转化生命所必需的小分子具有根本的重要性。从长远来看，了解生物系统中小分子还原的机制也可能导致用于化学合成的新催化剂，从而产生更广泛的影响。

DESCRIPTION (provided by applicant): In nitrogenases, iron-sulfur 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 iron-sulfur 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 specifi 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 low-coordinate iron, which can form Fe-N2 and Fe-H intermediates. In this hypothesis, sulfide donors in the FeMoco give reactive high-spin electronic configurations. We will test these ideas using synthetic iron clustes with combinations of sulfide, nitride, carbene and carbide bridges. Synthetic compounds with these features will show the feasibility of the proposed functional groups on iron-sulfur 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 iron-containing compounds with each of the following novel functionalities: unsaturated iron-sulfur clusters, iron-sulfide-hydride clusers, high- spin iron-carbene and carbide clusters, and N2-cleaving 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 solubilit in solvents that can be used at low temperature. Crystallography, kinetic studies, electrochemistry, and reactivity will be used to elucidate the atomic-level detail of the elementary steps of small-molecule binding and reduction. The synthetic complexes will be evaluated by ENDOR, infrared, Raman, M¿ssbauer, and X-ray 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 small-molecule reactions of iron-sulfur clusters. Therefore, there is fundamental importance in learning how the iron-sulfide cluster in nitrogenase binds and transforms small molecules that are essential for life. In the long run, understanding the mechanisms of small-molecule reduction in biological systems may also lead to new catalysts for use in chemical synthesis, giving an even broader impact.