Exploring the effects of multi-iron site cooperativity and second sphere ligand interactions on NN bond cleavage in high-spin iron complexes

探索多铁位点协同性和第二球配体相互作用对高自旋铁配合物中 NN 键断裂的影响

• 批准号: 9115473
• 负责人: Sean McWilliams
• 金额: $ 3.72万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115473
• 关键词: Acids; Active Sites; Alkali Metals; Ammonia; Area; Bacteria; Binding; Biological; Biology; Carbon Monoxide; Catalysis; Chemicals; Chemistry; Cleaved cell; Communities; Complex; Crown Ethers; Data Analyses; Development; Electron Nuclear Double Resonance; Electronics; Electrons; Environment; Enzymes; Fertilizers; Hydrogen; Imidazole; Industry; Investigation; Iron; Iron Compounds; Kinetics; Left; Life; Ligands; Metals; Methods; Molybdoferredoxin; Nitrogen; Nitrogenase; Organic Iron Compounds; Play; Preparation; Production; Protons; Reaction; Reagent; Reducing Agents; Reporting; Research; Roentgen Rays; Role; Site; Source; Sulfides; Sulfur; System; Techniques; Testing; Work; analog; base; biological systems; catalyst; cofactor; electronic structure; flexibility; improved; insight; interest; mutant; novel; oxidation; public health relevance; small molecule; spectroscopic survey

 DESCRIPTION (provided by applicant): Nitrogenase is an enzyme that is able to cleave the seemingly inert NN triple bond to form biologically available ammonia. The enzyme employs a structurally unprecedented Fe-S cluster, the iron-molybdenum cofactor, "FeMoco," to reduce N2 to NH3. Examination of fundamental Fe-N2 chemistry and how changes in coordination at Fe as well as the surrounding environment influence the ability of complexes to reduce N2 in will offer insight to the mechanism of nitrogenase. The effects of these features will be tested by synthesis of complexes that divide and simplify the FeMoco allowing for the study each feature has on Fe-N2 chemistry. The FeMoco contains the only example of a carbide in biology, however, how the carbide effects the Fe centers and their ability to reduce N2 remains speculative. Interactions of Fe-S and Fe-carbide clusters with N2 is unknown in synthetic complexes, and development of Fe-N2 complexes that do possess these ligands will provide a chemical basis for the proposed mechanisms of nitrogenase. Our guiding hypothesis is that N2 binds to the cluster through cleavage of either a Fe-C bond or Fe-S bond leading to a N2 complex that can interact with residues nearby the active site during enzyme turnover. In the proposed research, we plan to synthesize Fe-N2 complexes with novel functionalities: (1) second-sphere protic groups, which we hypothesize will allow for use of milder reagents for N2 reduction to ammonia compared with the systems reported previously that required strong acids, (2) introduction of electron-rich, anionic sulfur ligands should increase the donating abiliy of Fe making the bound N2 easier to reduce, and (3) formation of an Fe-carbide complex that also binds N2 to explore the role of the electron-rich carbide in nitrogenase through a synthetic analogue. Each new set of complexes will be examined through reactivity, kinetic, and X-ray crystallographic studies to understand how each impacts the interaction between Fe and dinitrogen. Study of these complexes through spectroscopic techniques such as EPR, ENDOR, and EXAFS will offer support for the chemical and structural interpretation of the data from nitrogenase.

 描述（由申请人提供）：固氮酶是一种能够裂解看似惰性的NN三键以形成生物可利用的氨的酶。该酶采用结构上前所未有的 Fe-S 簇，即铁-钼辅助因子“FeMoco”，将 N2 还原为 NH3。检查基本的 Fe-N2 化学以及 Fe 配位的变化以及周围环境如何影响复合物还原 N2 的能力，将为了解固氮酶的机制提供见解。这些特征的影响将通过合成复合物来测试，这些复合物可划分和简化 FeMoco，从而可以研究每个特征对 Fe-N2 化学的影响。 FeMoco 是生物学中唯一含有碳化物的例子，然而，碳化物如何影响 Fe 中心及其还原 N2 的能力仍然是推测。 Fe-S 和 Fe-碳化物簇与 N2 的相互作用在合成复合物中是未知的，开发具有这些配体的 Fe-N2 复合物将为所提出的固氮酶机制提供化学基础。我们的指导性假设是，N2 通过 Fe-C 键或 Fe-S 键的裂解与簇结合，形成 N2 复合物，该复合物可以在酶周转过程中与活性位点附近的残基相互作用。在拟议的研究中，我们计划合成具有新功能的Fe-N2配合物：（1）第二球质子基团，我们假设与之前报道的需要强酸的系统相比，它允许使用更温和的试剂将N2还原为氨，（2）引入富电子的阴离子硫配体应该增加Fe的供给能力，使结合的N2更容易还原，以及（3）形成 还结合 N2 的 Fe-碳化物复合物，通过合成类似物探索富电子碳化物在固氮酶中的作用。每一组新的配合物都将通过反应性、动力学和 X 射线晶体学研究进行检查，以了解每种配合物如何影响 Fe 和氮之间的相互作用。通过 EPR、ENDOR 和 EXAFS 等光谱技术对这些复合物的研究将为固氮酶数据的化学和结构解释提供支持。