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（由应用程序提供）：氮酶是一种能够清除看似惰性的NN三键以形成生物学上可用的氨的酶。该酶采用结构前所未有的Fe-S簇，铁溶血辅因子“ Femoco”，以将N2降低至NH3。检查基本FE-N2化学以及FE的配位变化以及周围环境如何影响复合物减少N2的能力的方法将为硝酸酶机制提供见识。这些特征的效果将通过合成复合物的合成来测试，这些复合物分裂和简化了femoco允许每个特征对FE-N2化学的研究。 Femoco包含生物学碳化物的唯一例子，但是，碳化物如何影响Fe中心及其减少N2的能力仍然是投机性的。 Fe-S和Fe-Carbide簇与N2的相互作用在合成复合物中尚不清楚，而确实拥有这些配体的Fe-N2复合物的发展将为提议的氮基酶机制提供化学基础。我们的指导假设是，N2通过Fe-C键或Fe-S键的切割与簇结合，导致N2复合物在酶离职期间与活性位点附近的残留物相互作用。 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 miller reagents for N2 reduction to ammonia compared with the systems reported previously that required strong acids, (2) introduction of electronic-rich, anionic sulfur ligands should increase the donating abiliy of Fe making the bound N2 easier to reduce, and (3) formation Fe-Carbide复合物也结合N2，通过合成类似物探索富含电子碳化物的氮化酶的作用。每种新的复合物将通过反应性，动力学和X射线晶体学研究进行检查，以了解每种晶体如何影响Fe与Dinitrogen之间的相互作用。通过EPR，ENDOR和EXAFS等光谱技术对这些复合物进行研究，将为氮酶数据的化学和结构解释提供支持。