Low-Coordinate Synthetic Models for Nitrogenase Activity

固氮酶活性的低坐标合成模型

基本信息

批准号：
9751869
负责人：
PATRICK L HOLLAND
金额：
$ 32.64万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
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/9751869
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 metalloenzyme mutant oxidation spectroscopic data spectroscopic survey

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 metalloenzyme mutant oxidation spectroscopic data spectroscopic survey

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项目摘要

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.

项目摘要 N2对NH3的生物学还原仅由氮酶进行，这些酶具有异常的铁 - 硫化物 - 碳化物簇作为活性位点。我们在这里专注于铁螺旋果中的Femoco辅因子硝基化酶通过未知机制实现了这种多电体催化反应。 Femoco是生物化学中碳化物（正式C4-）的唯一例子。大概是这个碳化物通过Fe-CH3，Fe-Ch2和Fe-CH中间体插入，这些中间体在铁硫化物中前所未有化合物。 Femoco中异常的协调化学大概有助于其减少的能力 N2，但在生物合成和催化途径中缺乏推定物种的先例会阻碍评估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。移动场地向前需要新的协调化学，以阐明相关簇的性质和反应性。我们的指导假设是，具有笨重配体的合成FES和FEC簇将具有激活的Femoco的结构，光谱和反应性属性。因为这些集群有明确已知的环境可以建立特定的光谱特征结构特征，该特征首先将结构和光谱链接起来。另外，它们可用于测试机械步骤的可行性，例如Fe-C键裂解，Fe-S键裂解和Fe-N2键形成。在拟议的研究中，我们将与铁硫和铁碳核合成新的簇化合物。一个重点是可以结合N2和其他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，并将探索其光谱特性和反应。第二个重点在具有不同数量的氢原子的Fe-C键的系统系列中，在碳化物桥的簇中达到高潮。我们建议将铁甲基，卡宾，卡比恩和碳化物化合物将阐明高自旋铁簇中不同Fe-C键的基本面类似于Femoco。氢原子的添加和去除互连这些物种，模仿步骤在Femoco的生物合成中。化合物中Fe-C键的形成和裂解也是与氮酶活性的机理相关，并将使用反应性和光谱镜来解决研究。与从事氮酶的领先光谱学家的合作，可以增强相关性和我们与酶的比较严格。氮酶很棒具有带有碳化物的独特辅因子结构，并且具有与N2相互作用的罕见能力。然而，联系和理解这些观察结果需要在FES簇的基本化学方面取得进步。该项目将提供理解Femoco所需的化学先例。