Multi-nuclear Iron Clusters as Biomimics of Nitrogenase Enzyme Metallocofactors

多核铁簇作为固氮酶金属辅因子的仿生

• 批准号: 10700023
• 负责人: Trevor Latendresse
• 金额: $ 6.95万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700023
• 关键词: Acetylene; Active Sites; Affect; Alkanes; Amines; Architecture; Atmosphere; Binding; Biological; Biological Availability; Biological Models; Biology; Biomimetics; Cells; Chemicals; Chemistry; Complex; Development; Electrolyses; Electron Spin Resonance Spectroscopy; Elements; Enzymes; Event; Face; Generations; Goals; Human; Ions; Iron; Life; Ligands; Magnetometries; Mediating; Mediation; Methods; Modeling; Molecular; Molecular Structure; Monitor; Mononuclear; Nature; Nitrogen; Nitrogenase; Nuclear; Nucleic Acids; Oxidants; Oxidation-Reduction; Oxides; Periodicity; Process; Production; Program Description; Property; Proteins; Protons; Reaction; Reagent; Reducing Agents; Research; Role; Route; Site; Source; Spectrum Analysis; Structure; Study models; Sulfides; System; Testing; Transition Elements; Work; X ray diffraction analysis; analog; biological systems; cofactor; design; electronic structure; functional mimics; metal complex; role model; sample fixation; scaffold; small molecule

Project Summary/Abstract Entry of nitrogen into the biosphere is crucial for the development and sustainability of life, as this element is utilized in the development of proteins, nucleic acids, and other cell constituents. Nature uses nitrogenase enzymes to mediate the transformation of the bioinactive atmospheric N2 into more reactive nitrogen sources such as NH3. Ubiquitous to all nitrogenase enzymes are multi-nuclear transition metal cofactors which act as the active site for N2 binding, reduction, and transformation into its reduced substrates. Despite the foundational role of the N2 fixation cycle to biology, the detailed mechanism of how nitrogenase enzyme metallocofactors facilitate N2 fixation is largely uncertain. Synthetic chemists are actively pursuing mechanistic elucidation of the N2 fixation by nitrogenase metallocofactors by using coordination chemistry to design molecular architectures which can bind and reduce N2. Significant progress has been made in this regard, especially in terms of the reduction of N2 with mononuclear transition metal compounds, but it is in question whether mononuclear systems provide accurate models for polynuclear metallocofactor sites. To this end, the use of polynuclear high-spin transition metal complexes as functional models for nitrogenase metallocofactors have been much less explored. The research program described herein involves the synthesis, characterization, and reactivity of new all monovalent [Fe3] molecular architectures which we propose could be functional models to explore the mechanism of the Fe- Mo cofactor (FeMoco) of nitrogenase. Initially, a new trianionic, hexadentate, ligand scaffold [NPL]3- will be synthesized which can support three monovalent first-row transition metal ions. The trimetallation of [NPL]3- with monovalent Fe(I) will be carried out to form the proposed monovalent tri-iron complex, (NPL)Fe3. Single-crystal X-ray diffraction, SQUID magnetometry, EPR spectroscopy, and cyclic voltammetry will be used to determine the structure, spin-state, and redox properties of (NPL)Fe3. The reactivity of the new [Fe3] cluster will be evaluated by reacting (NPL)Fe3 with simple chemical oxidants and nitrogenase substrates (i.e. N2 and CO). Compound (NPL)Fe3 will be subjected to reactions with oxidative N-group transfer reagents or N2 surrogates to establish the N-bound intermediates involved on the way to full N2 conversion. The oxidative group transfer reactivity of (NPL)Fe3 will also be explored using S-, O-, and C- group transfer reagents where the proposed sulfide complex, [(NPL)Fe3(µ3-S)]-, will be used to model the role of sulfide ligands in the N2 fixation of FeMoco. We will synthesize mono- and poly-hydride complexes, (NPL)Fe3H1-3, which could act as synthetic models for the E4 state of FeMoco, which is the intermediate proposed to bind N2. The reactivity of the hydride complexes will be explored with nitrogenase substrates such as N2, CO, and acetylene and the formation of the reduced amine of alkane substrates will be monitored. For promising model complexes, the efficacy of catalytic N2 or CO reduction will be investigated in the presence of a suitable chemical H+/e- sources or via electrolysis. If successful, these studies are predicted to elucidate key mechanistic steps of the N2 reduction process of FeMoco.

项目概要/摘要 氮进入生物圈对于生命的发展和可持续性至关重要，因为该元素 用于蛋白质、核酸和其他细胞成分的开发 大自然使用固氮酶。 酶介导将无生物活性的大气 N2 转化为更具活性的氮源 多核过渡金属辅助因子（例如 NH3）普遍存在于所有固氮酶中。 尽管具有基础作用，但 N2 结合、还原和转化为其还原底物的活性位点。 N2 固定循环对生物学的影响，固氮酶金属辅因子如何促进的详细机制 N2 固定在很大程度上是不确定的。合成化学家正在积极寻求 N2 固定的机制阐明。 通过固氮酶金属辅因子，使用配位化学设计分子结构，可以 结合和减少 N2 在这方面已经取得了重大进展，特别是在减少 N2 方面。 与单核过渡金属化合物，但单核系统是否提供存在问题 多核金属辅因子位点的精确模型为此，使用多核高自旋跃迁。 金属配合物作为固氮酶金属辅因子的功能模型的研究较少。 本文描述的研究计划涉及新的全单价的合成、表征和反应性 我们提出的[Fe3]分子结构可以作为功能模型来探索Fe-的机制 固氮酶的 Mo 辅因子 (FeMoco) 最初将是一种新的三阴离子六齿配体支架 [NPL]3-。 合成了可以负载三个一价第一行过渡金属离子的[NPL]3-的三金属化。 一价 Fe(I) 将被形成所提出的一价三铁络合物，(NPL)Fe3。 X 射线衍射、SQUID 磁力测定、EPR 光谱和循环伏安法将用于确定 (NPL)Fe3 的结构、自旋态和氧化还原性质将评估新的 [Fe3] 团簇的反应性。 通过 (NPL)Fe3 与简单的化学氧化剂和固氮酶底物（即 N2 和 CO）反应。 (NPL)Fe3 将与氧化性 N 基团转移试剂或 N2 替代物发生反应，以建立 N-结合中间体参与 N2 完全转化的氧化基团转移反应性。 (NPL)Fe3 还将使用 S-、O-和 C-基团转移试剂进行探索，其中所提出的硫化物络合物， [(NPL)Fe3(μ3-S)]-，将用于模拟硫化物配体在 FeMoco 的 N2 固定中的作用。 一氢化物和多氢化物配合物，(NPL)Fe3H1-3，可以作为 FeMoco E4 态的合成模型， 这是提议结合 N2 的中间体。将探索氢化物配合物的反应性。 固氮酶底物如 N2、CO 和乙炔以及烷烃还原胺的形成 对于有前景的模型复合物，将监测催化 N2 或 CO 还原的功效。 在合适的化学 H+/e- 源存在下或通过电解进行研究 如果成功，这些研究。 预计将阐明 FeMoco N2 还原过程的关键机制步骤。

项目成果

Synthesis, Characterization, and the Effect of Lewis Bases on the Nuclearity of Iron Alkoxide Complexes.

路易斯碱的合成、表征以及对铁醇盐配合物核性的影响。

• 发表时间: 2024-04-29
• 影响因子: 4.6
• 作者: Gwinn, Reilly K;Williams, Matthew;Latendresse, Trevor P;Slebodnick, Carla;Troya, Diego;Tarannum, Tasnema;Thornton, Diana A
• 通讯作者: Thornton, Diana A