Low-Coordinate Synthetic Models for Nitrogenase Activity

固氮酶活性的低坐标合成模型

• 批准号: 7901205
• 负责人: PATRICK L HOLLAND
• 金额: $ 10.45万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901205
• 关键词: Address; Affect; Amaze; Ammonia; Anabolism; Bacterial Transformation; Binding; Biochemistry; Characteristics; Chemistry; Classification; Cleaved cell; Complex; Electron Transport; Electronics; Electrons; Enzymes; Evaluation; Goals; Hydrogen; Hydrogen Bonding; Ions; Iron; Iron Compounds; Kinetics; Lead; Learning; Ligands; Literature; Location; Metals; Methods; Modeling; Molybdenum; Molybdoferredoxin; Mutation; Nitrogen; Nitrogenase; Organic Iron Compounds; Oxidation-Reduction; Pattern; Plants; Process; Property; Protein Binding; Proteins; Protons; Reaction; Site; Substrate Specificity; Work; base; catalyst; protonation; research study; sample fixation; trend

Bacterial nitrogenases catalyze the reduction ("fixation") of N/2 to ammonia, an amazing process that gives the precursor to all nitrogen-containing biomolecules. Because it is the ultimate multielectron reduction, discovery of the detailed mechanism of nitrogenase is a great challenge in biochemistry. N2 reduction occurs at a metal cluster called the FeMoco. After addition of electrons and protons, the FeMoco somehow binds, breaks, and protonates N2 to NH4*. Mutations near the FeMoco show that N2 and other substrates bind near the iron-rich center of the cluster. Based on literature crystallographic, spectroscopic, and mechanistic studies on nitrogenase, we have formulated a reasonable iron-based mechanism for reduction and N2 binding. This mechanism, based on low-coordinate iron, serves as our guiding hypothesis. Key intermediates have iron with only 3 or 4 attachments, and others with Fe-H bonds. However, the literature has few synthetic 3-coordinate iron compounds, and no Fe-H complexes with a coordination number of four or less. This proposal describes the systematic study of synthetic low-coordinate iron compounds: their properties, spectroscopic signatures, reactivity toward nitrogenase substrates, and characteristic reaction patterns. Experiments are chosen to address several steps of the hypothetical mechanism, including reductive activation, N2 binding, N2 reactions and cleavage, and N-H bond formation. Because isolated Fe-H complexes completely break multiple bonds, they will be studied as reactivity models for nitrogenase intermediates. Multimetallic complexes with constrained geometry will show the arrangement most conducive to N2 cleavage. Mechanistic studies on key reactions will clarify allowed and forbidden reactions of iron atoms like those in the hypotheticaL FeMoco mechanism. These studies will elucidate the fundamentals of low-coordinate iron chemistry, which is necessary to understand the workings of the FeMoco and large synthetic clusters.

细菌氮酶将N/2的还原（“固定”）催化为氨，这是一个惊人的 为所有含氮生物分子提供前体的过程。因为这是最终的多电源减少，所以发现氮酶详细机制是生物化学的巨大挑战。 N2还原发生在称为Femoco的金属簇下。添加电子和质子后，femoco以某种方式结合，断裂和质子化N2与NH4*。 Femoco附近的突变表明N2和其他底物在簇的铁中心附近结合。基于文献晶体学，光谱和硝化酶的机理研究，我们制定了一种合理的基于铁的减少和N2结合的机制。这种基于低坐标铁的机制是我们的指导假设。关键中间体具有只有3或4个附件的铁，而其他则具有Fe-H键。但是，文献几乎没有合成的3坐标铁化合物，而没有四个或更少的配位数的Fe-H复合物。 该建议描述了合成低坐标铁化合物的系统研究： 它们的特性，光谱特征，对氮酶底物的反应性和 特征反应模式。选择实验以解决假设机制的几个步骤，包括还原激活，N2结合，N2反应和裂解以及N-H键的形成。由于分离的Fe-H复合物完全断裂多个键，因此将研究它们作为氮酶中间体的反应性模型。具有约束几何形状的多功能复合物将显示最有利于N2裂解的布置。关于关键反应的机理研究将阐明允许的和类似于假设的Femoco机制的铁原子的禁止反应。这些研究将阐明低坐标铁化学的基本原理，这对于了解Femoco和大型合成簇的起作用是必不可少的。