Scaffold-based Biomimetics of Fe-Hydrogenase and Nitrogenase (FeMoco): Interrogating Dynamics, Protein Matrix Effects, and Carbide Motifs

基于支架的铁氢化酶和固氮酶 (FeMoco) 仿生学：探究动力学、蛋白质基质效应和碳化物基序

• 批准号: 2109175
• 负责人: Michael Rose
• 金额: $ 45万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2109175&HistoricalAwards=false
• 关键词: Scaffold; based; Biomimetics; Fe; Hydrogenase

With the support of the Chemistry of Life Processes Program in the Chemistry Division, Dr. Michael Rose from University of Texas at Austin investigates the role of scaffold-based ligands and carbides in supporting biomimetic models of the enzymes hydrogenase and nitrogenase. These enzymes catalyze fundamental reactions that underpin living systems in numerous environments. Hydrogenases use dihydrogen (H2) produced by microbiological fermenters to reduce carbon dioxide (CO2) in organisms called methanogens. Nitrogenases convert atmospheric dinitrogen (N2, which makes up 80% of the air) into ammonia (NH3), which is essential for plant growth. These two chemical reactions are critical to environmental and green chemistry. Studies of the molecular structures and mechanisms of the active sites of these enzymes are critical to the design, synthesis and understanding of earth abundant and sustainable catalysts that will carry out these reactions. This research will be implemented by a diverse pool of undergraduate researchers from UT Austin and REU programs. These students will learn laboratory and computational skills that will prepare them for graduate study and/or STEM careers in. Dr. Rose will continue to focus on raising and improving safety awareness in the Chemistry Department including through his support of the Chemistry Student Safety Organization (CSSO), which promotes best practices in laboratory safety across the Department. The H2fromH2O educational program will continue to operate in local schools and at local events; a hands-on water-splitting experiment delivered through the program emphasizes the importance of renewable fuels and the potential of sunlight-to-hydrogen conversion as an energy paradigm. More specifically, this research will investigate the use of supramolecular scaffold ligands based on anthracene and related units that support the chemically complex structure of [Fe]-hydrogenase. This enzyme uses a low-spin Fe(II)-dicarbonyl bound to thiolate, pyridone and organometallic acyl donor to perform H2 activation and hydride transfer. The proposed research aims to discover how molecular flexibility in the scaffold can accelerate H2 activation and catalysis. This will be achieved by installing flexible ‘anthranoids’ such as thianthrene and selenthrene in the scaffold to (i) enable more facile access to strained and reactive ground state geometries, and/or (ii) lower the energy of strained transition states to accelerate catalysis. Secondly, the research will aim to install molecular Fe complexes inside a well-characterized protein scaffold — namely, β-lactoglobulin (βLG). While it has been demonstrated that Fe complexes are catalytically competent, the research will endeavor to enhance catalysis by building structurally well-defined interactions (H-bonding, ion pairs, molecular motion) between the metal site and proteinaceous units. This research also aims to synthesize carbide-based Fe clusters relevant to the nitrogenase active site. Presently there are no known synthetic methods to access iron-sulfur-carbide clusters. The project will utilize ‘historical’ iron-carbide-carbonyl clusters as synthons for sulfur and thiolate incorporation in new Fe model complexes. Both electrophilic (S2Cl2, RS–Cl) and nucleophilic (Na2S, RS–) addition mechanisms will be explored, with an emphasis on using under-coordinated versions (non-Wade-Mingos rules) of the iron-carbide-carbonyl clusters for reactive sulfur addition.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系生命过程化学项目的支持下，德克萨斯大学奥斯汀分校的 Michael Rose 博士研究了基于支架的配体和碳化物在支持氢化酶和固氮酶的仿生模型中的作用。这些酶催化支撑多种环境中生命系统的基本反应。氢化酶利用微生物发酵罐产生的氢气 (H2) 来减少称为产甲烷菌的生物体中的二氧化碳 (CO2)。 固氮酶将大气中的二氮（N2，占空气的 80%）转化为氨 (NH3)，这是植物生长所必需的。这两个化学反应对于环境和绿色化学至关重要。对这些酶活性位点的分子结构和机制的研究对于设计、合成和理解地球上丰富且可持续的催化剂至关重要，这些催化剂将进行这些反应。这项研究将由来自 UT Austin 和 REU 项目的不同本科生研究人员实施。这些学生将学习实验室和计算技能，为他们的研究生学习和/或 STEM 职业做好准备。Rose 博士将继续致力于提高和提高化学系的安全意识，包括通过他对化学学生安全组织 (CSSO) 的支持，该组织在整个系内推广实验室安全的最佳实践。 H2fromH2O 教育计划将继续在当地学校和当地活动中开展；通过该计划进行的水分解实践实验强调了可再生燃料的重要性以及将阳光转化为氢气作为能源范例的潜力。更具体地说，本研究将研究基于蒽和支持[Fe]-氢化酶化学复杂结构的相关单元的超分子支架配体的使用。该酶利用与硫醇盐、吡啶酮和有机金属酰基供体结合的低自旋 Fe(II)-二羰基来进行 H2 活化和氢化物转移。拟议的研究旨在发现支架中的分子灵活性如何加速 H2 的活化和催化。这将通过在支架中安装灵活的“蒽醌”（例如噻蒽醌和硒烯）来实现，以（i）更容易地获得应变和反应性基态几何形状，和/或（ii）降低应变过渡态的能量以加速催化。其次，该研究的目标是将分子铁复合物安装在一个充分表征的蛋白质支架内，即β-乳球蛋白（βLG）。虽然已经证明铁配合物具有催化能力，但该研究将努力通过在金属位点和蛋白质单元之间建立结构明确的相互作用（氢键、离子对、分子运动）来增强催化作用。这项研究还旨在合成与固氮酶活性位点相关的碳化物基铁簇。目前还没有已知的合成方法来获得铁碳化硫簇。该项目将利用“历史上的”碳化铁-羰基簇作为合成子，将硫和硫醇盐掺入新的铁模型复合物中。将探索亲电（S2Cl2、RS–Cl）和亲核（Na2S、RS–）加成机制，重点是使用铁碳化物羰基团簇的欠配位版本（非 Wade-Mingos 规则）进行活性硫加成。该奖项反映了 NSF 的法定使命，并通过使用基金会的知识进行评估，被认为值得支持。 优点和更广泛的影响审查标准。

项目成果

Distal scaffold flexibility accelerates ligand substitution kinetics in manganese( i ) tricarbonyls: flexible thianthrene versus rigid anthracene scaffolds

远端支架灵活性加速了三羰基锰 (i) 中的配体取代动力学：柔性噻蒽与刚性蒽支架

• DOI: 10.1039/d2dt04048d
• 发表时间: 2023
• 期刊: Dalton Transactions
• 影响因子: 4
• 作者: Labrecque, Jordan;Cho, Yae-In;McIntosh, Daniel K.;Agboola, Faridat;Rose, Michael J.
• 通讯作者: Rose, Michael J.