Low-Coordinate Synthetic Models for Nitrogenase Activity

固氮酶活性的低坐标合成模型

• 批准号: 9892347
• 负责人: PATRICK L HOLLAND
• 金额: $ 8.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892347
• 关键词: Acetylene; Active Sites; Address; Amaze; Ammonia; Anabolism; Atmosphere; Behavior; Binding; Biochemistry; Bioinorganic Chemistry; Biological; Biology; Chemicals; Cleaved cell; Communities; Complement component C4a; Complex; Complication; Coupling; Crystallization; Crystallography; Data; Electrochemistry; Electron Nuclear Double Resonance; Electron Transport; Environment; Enzyme Reactivation; Enzymes; Goals; Iron; Kinetics; Knowledge; Lead; Learning; Life; Link; Modeling; Molybdenum; Nitrogen; Nitrogen Fixation; Nitrogenase; Nuclear; Pathway interactions; Periodicity; Process; Protein Conformation; Proteins; Reaction; Research; Roentgen Rays; Role; Site; Solubility; Solvents; Specific qualifier value; Spectrum Analysis; Structure; Sulfides; Sulfur; Support Groups; Testing; Time; Transcend; Work; absorption; adduct; analog; biological systems; carbene; catalyst; chemical synthesis; cofactor; cold temperature; electron nuclear double resonance spectroscopy; fascinate; functional group; insight; novel; oxidation; small molecule; spectroscopic data; spectroscopic survey

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.

项目摘要 在氮酶中，铁硫簇通过执行 将N2降低到NH3。因此，该酶显示了ironsulfur的惊人催化潜力 生物系统中的簇。除了其独特的降低N2的能力外，Femoco的活性位点 氮酶具有碳化物（C4），这是一种在生物化学中的新特征。生物合成中的中间体 和催化机制可能具有氢化物，碳烯，N2和氢津部分，这是未知的 在其他酶中。学习氮酶结构和功能之间的关系由 与Femoco具有特定相似之处的合成分子。尽管它们是简化的，但他们做到了 可以一次测试一个结构特征，而无需其他辅助因子和蛋白质的并发症。 我们的指导假设是碳化物固定并释放低坐标铁，可以形成Fen2和 FEH中间体。在这个假设中，股骨中的硫化物供体给出了反应性高速电子电子 配置。我们将使用与硫化物，氮化物，氮化物组合的合成铁簇测试这些想法 卡宾桥和卡比德桥。具有这些功能的合成化合物将显示提出的可行性 iRonsulfur簇上的官能团，建立这些官能团的光谱特征，并 证明其行为是否与Femoco生物合成和机制的模型一致。 在拟议的研究中，我们将与每种的合成铁化合物创建合成的化合物 以下新型功能：不饱和的ironsulfur簇，ironsulfidehydride簇，高 旋转铁赛和碳化物簇，以及N2裂解铁配合物。隔离和 通过使用笨重的支撑组，使这些化合物的表征成为可能。笨重 组还促进结晶，并提高可在低温下使用的溶液中的溶解度。 晶体学，动力学研究，电化学和反应性将用于阐明原子细节 小分子结合和还原的基本步骤。合成复合物将通过 Endor，Infrared，Raman，Mössbauer和X射线抽象光谱镜头，以提供在该链接之间 新型模型化合物的结构和氮酶的已知数据。 我们预计拟议的工作将导致氮酶反应途径的宝贵先例。 尽管对生物无机化学中多电体氧化反应的机制知之甚少，但 关于多电子生物学降低的知识远远落后，特别需要 关于铁硫簇的小分子反应的研究。因此，在 了解氮基酶中的Ironsulfide簇如何结合并转化针对的小分子 生活。从长远来看，了解生物系统减少小分子的机制也可能 导致新的催化剂用于化学合成，从而产生更广泛的影响。