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博士研究了骨架配体和碳化物在支持氢酶和固氮酶的仿生模型中的作用。这些酶催化在许多环境中支撑生命系统的基本反应。氢酶利用微生物发酵产生的二氢(H2)来减少被称为产甲烷菌的生物体中的二氧化碳(CO2)。固氮酶将大气中的氮素(占空气的80%)转化为氨(NH3)，这是植物生长所必需的。这两个化学反应对环境和绿色化学至关重要。研究这些酶活性中心的分子结构和作用机理，对于设计、合成和理解进行这些反应的地球上丰富和可持续的催化剂至关重要。这项研究将由来自德克萨斯大学、奥斯汀和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，为研究生学习和/或STEM职业生涯做好准备。Rose博士将继续致力于提高和改善化学系的安全意识，包括通过他对化学学生安全组织(CSSO)的支持，CSSO在整个化学系推广实验室安全的最佳做法。来自水的氢气教育计划将继续在当地学校和当地活动中进行；通过该计划进行的动手水分裂实验强调了可再生燃料的重要性，以及将太阳能转换为氢气作为能源范例的潜力。更具体地说，这项研究将调查基于菲和相关单元的超分子支架配体的使用，这些单元支持[Fe]-氢酶的化学复杂结构。这种酶使用低自旋Fe(II)-二羰基结合到硫酸盐、吡啶酮和有机金属酰基供体上来执行氢活化和氢化物转移。这项拟议的研究旨在发现支架中的分子柔性如何加速氢气的激活和催化。这将通过在支架中安装如硫杂菲和硒的灵活的‘菲’类化合物来实现，以(I)允许更容易地访问应变和反应基态几何构型，和/或(Ii)降低应变过渡态的能量以加速催化。其次，这项研究的目标是将分子铁络合物安装在一种具有良好特性的蛋白质支架内--即β-乳球蛋白(βLG)。虽然已经证明了铁配合物具有催化活性，但该研究将努力通过在金属中心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。本研究还旨在合成与固氮酶活性中心相关的碳化物基铁簇合物。目前还没有已知的合成方法来获得铁-硫-碳化物簇合物。该项目将利用历史上的铁-碳化物-羰基簇合物作为合成子，在新的铁模型络合物中结合硫和硫酸盐。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-羰基簇合物的不协调版本(非Wade-Mingos规则)进行活性硫添加。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.