Low-Coordinate Synthetic Models for Nitrogenase Activity

固氮酶活性的低坐标合成模型

• 批准号: 10218187
• 负责人: PATRICK L HOLLAND
• 金额: $ 32.4万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218187
• 关键词: Active Sites; Address; Alkynes; Amaze; Ammonia; Anabolism; Behavior; Binding; Binding Sites; Biochemistry; Biological; Carbon; Catalysis; Characteristics; Chemicals; Chemistry; Cleaved cell; Collaborations; Complex; Data; Electron Nuclear Double Resonance; Environment; Enzymes; Excision; Funding; Hydrogen; Individual; Ions; Iron; Life; Ligands; Link; Literature; Metals; Modeling; Molybdenum; Molybdoferredoxin; Nature; Nitrogen; Nitrogenase; Pathway interactions; Planet Earth; Process; Property; Reaction; Research; Role; Series; Shapes; Site; Solvents; Spectrum Analysis; Structure; Sulfides; Sulfur; Testing; Thermodynamics; Time; Work; analog; biological systems; carbene; cofactor; electron nuclear double resonance spectroscopy; feasibility testing; metalloenzyme; mutant; oxidation; spectroscopic data; spectroscopic survey

Project Summary Biological reduction of N2 to NH3 is performed solely by nitrogenase enzymes, which have unusual iron- sulfide-carbide clusters as active sites. We focus here on the FeMoco cofactor in iron-molybdenum nitrogenase, which accomplishes this multielectron catalytic reaction through an unknown mechanism. The FeMoco is the only example of a carbide (formally C4–) in biological chemistry. This carbide is presumably inserted by way of Fe-CH3, Fe-CH2, and Fe-CH intermediates that are unprecedented in iron-sulfide compounds. The unusual coordination chemistry in the FeMoco presumably contributes to its ability to reduce N2, but the lack of precedents for the putative species in the biosynthetic and catalytic pathways hinders the ability to evaluate whether the proposed mechanisms are reasonable. Similarly, the interpretation of spectroscopic data is difficult because of the lack of related compounds in the literature. Moving the field forward requires new coordination chemistry that elucidates the properties and reactivity of relevant clusters. Our guiding hypothesis is that synthetic FeS and FeC clusters with bulky supporting ligands will have structural, spectroscopic, and reactivity attributes of activated FeMoco. Because these clusters have environments that are known unambiguously, they can establish the spectroscopic signatures of specific structural features, which links structure and spectroscopy firmly. In addition, they can be used to test the feasibility of mechanistic steps such as Fe-C bond cleavage, Fe-S bond cleavage, and Fe-N2 bond formation. In the proposed research, we will synthesize new cluster compounds with iron-sulfur and iron-carbon cores. One focus is iron-sulfide clusters that can bind N2 and other nitrogenase substrates. We will prepare the first iron-sulfide clusters that bind N2, and will explore their spectroscopic properties and reactions. A second focus is on a systematic series of compounds with Fe-C bonds having different numbers of hydrogen atoms, and culminating in carbide-bridged clusters. We propose that comparison of iron methyl, carbene, carbyne, and carbide compounds will elucidate the fundamentals of different Fe-C bonds in high-spin iron clusters resembling the FeMoco. Addition and removal of hydrogen atoms interconverts these species, mimicking steps in the biosynthesis of the FeMoco. The formation and cleavage of Fe-C bonds in the compounds is also relevant to the mechanism of nitrogenase activity, and will be addressed using reactivity and spectroscopic studies. Collaborations with leading spectroscopists who work on nitrogenase enhances the relevance and rigor of our comparisons to the enzyme. Nitrogenase is amazing because it carries out a thermodynamically demanding multielectron reduction, it possesses a unique cofactor structure with a carbide, and it has the rare ability to interact with N2. However, linking and understanding these observations requires advances in the fundamental chemistry of FeS clusters. This project will provide the chemical precedents that are needed to comprehend the FeMoco.

项目概要 N2 到 NH3 的生物还原仅由固氮酶完成，固氮酶具有不寻常的铁- 我们在这里关注铁钼中的 FeMoco 辅助因子。 固氮酶，它通过未知的机制完成这种多电子催化反应。 FeMoco 是生物化学中碳化物（正式形式为 C4-）的唯一例子。这种碳化物可能是碳化物。 通过 Fe-CH3、Fe-CH2 和 Fe-CH 中间体插入，这在硫化铁中是前所未有的 FeMoco 中不寻常的配位化学本质上有助于其还原的能力。 N2，但在生物合成和催化途径中缺乏假定物种的先例阻碍了 评估所提出的机制是否合理的能力，同样，解释。 由于文献中缺乏相关化合物，光谱数据很困难。 向前发展需要新的配位化学来阐明相关簇的性质和反应性。 我们的指导性假设是，具有庞大支持配体的合成 FeS 和 FeC 簇将具有 活化的 FeMoco 的结构、光谱和反应特性因为这些团簇具有。 在明确已知的环境中，他们可以建立特定的光谱特征 结构特征，将结构和光谱牢固地联系起来，此外，它们还可用于测试。 Fe-C 键断裂、Fe-S 键断裂和 Fe-N2 键形成等机械步骤的可行性。 在拟议的研究中，我们将合成具有铁硫和铁碳核心的新型簇状化合物。 一个焦点是可以结合 N2 和其他固氮酶底物的铁硫化物簇，我们将准备第一个。 结合 N2 的铁硫化物簇，并将探索它们的光谱特性和反应。 是具有不同氢原子数的 Fe-C 键的系统系列化合物，并且 我们建议对甲基铁、卡宾、卡炔和碳烯进行比较。 碳化物化合物将阐明高自旋铁簇中不同 Fe-C 键的基本原理 重新组装 FeMoco，氢原子的添加和去除使这些物质相互转化，模仿步骤。 在 FeMoco 的生物合成过程中，化合物中 Fe-C 键的形成和断裂也是如此。 与固氮酶活性机制相关，并将使用反应性和光谱来解决 与从事固氮酶研究的领先光谱学家的合作增强了相关性和 我们与酶的比较的严格性。 固氮酶是令人惊奇的，因为它进行热力学要求的多电子还原，它 具有独特的碳化物辅助因子结构，并且具有罕见的与 N2 相互作用的能力。 联系和理解这些观察结果需要在 FeS 团簇的基础化学方面取得进展。 该项目将提供理解 FeMoco 所需的化学先例。