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: 10536804
• 负责人: Trevor Latendresse
• 金额: $ 6.72万
• 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/10536804
• 关键词: Acetylene; Active Sites; Affect; Alkanes; Amines; Architecture; Binding; Biological; Biological Models; Biology; Biomimetics; Cells; Chemicals; Chemistry; Complex; Crystallization; Development; Electrolyses; Electron Spin Resonance Spectroscopy; Elements; Enzymes; Event; Face; Foundations; Generations; Goals; Human; Ions; Iron; Life; Ligands; Magnetometries; Mediating; Mediation; Methods; Modeling; Molecular; Molecular Structure; Monitor; Mononuclear; Nature; Nitrogen; Nitrogenase; Nucleic Acids; Oxidants; Oxidation-Reduction; Oxides; Periodicity; Process; Production; 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; programs; 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.

项目摘要/摘要 将氮的进入生物圈进入生物圈至关重要，因为该元素是 用于蛋白质，核酸和其他细胞构建体的发展。大自然使用氮酶 酶介导生物启用性大气N2转化为更具反应性的氮源 例如NH3。无处不在的所有氮酶是多核过渡金属辅因子 N2结合，还原和转化为其还原底物的活性位点。尽管有基础 N2固定周期的生物学，这是氮酶如何制备的氮素酶如何制备的详细机制 N2固定在很大程度上不确定。合成化学家正在积极追求N2固定的机械阐明 通过氮酶金属合作活性剂，通过使用协调化学设计分子体系结构可以 绑定并减少N2。在这方面取得了重大进展，尤其是在减少N2方面 使用单核过渡金属化合物，但疑问是单核系统是否提供 多核金属生物活性位点的精确模型。为此，使用多核高旋转过渡 金属复合物作为氮酶金属酶活能力的功能模型的探索程度要少得多。这 本文描述的研究计划涉及新的所有单价的综合，表征和反应性 [FE3]我们提出的分子体系结构可能是探索Fe-机制的功能模型 氮酶的mo辅因子（femoco）。最初，一种新的三角离子，六边形，配体脚手架[npl] 3-将是 合成的，可以支持三个单价的第一行过渡金属离子。 [npl] 3-的修剪 将进行单价Fe（i），以形成拟议的单价三铁复合物（NPL）Fe3。单晶 X射线衍射，鱿鱼磁力测定法，EPR光谱和环状伏安法将用于确定 （NPL）Fe3的结构，自旋状态和氧化还原特性。将评估新[FE3]群集的反应性 通过与简单的化学氧化物和氮酶底物（即N2和CO）反应（NPL）Fe3。化合物 （NPL）FE3将对氧化物N组转移试剂或N2替代物进行反应，以建立 N-BOND中间体在进行全N2转换的路上涉及。氧化群转移反应性 （NPL）FE3还将使用S-，O-和C组转移试剂进行探索，其中提出的硫化物络合物，即 [（NPL）Fe3（µ3-S）] - 将用于模拟硫化物配体在Femoco N2固定中的作用。我们将合成 单和多氢化物复合物，（NPL）Fe3H1-3，可以充当E4 Femoco状态的合成模型， 这是提议结合n2的中间体。 Hydrode复合物的反应性将与 N2，CO和乙炔等氮酶底物以及烷基还原胺的形成 将监视底物。对于有望模型复合物，催化N2或CO的效率将是 在存在合适的H+/E-源或通过电解的情况下进行了研究。如果成功，这些研究 预计将阐明Femoco的N2还原过程的关键机械步骤。