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

在化学部门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氮化酶的仿生模型中的作用。这些酶催化基本反应，在许多环境中支撑生命系统。氢化酶利用微生物发酵罐产生的二氢（H2）来减少甲烷菌体内的二氧化碳（CO2）。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。这两种化学反应对环境和绿色化学至关重要。研究这些酶的分子结构和活性位点的机制对于设计、合成和理解将进行这些反应的地球丰富和可持续的催化剂至关重要。这项研究将由来自德州大学奥斯汀分校和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，该组织在整个化学系推广实验室安全的最佳实践。h2frommh2o教育项目将继续在当地学校和当地活动中开展；通过该项目进行的实际水分解实验强调了可再生燃料的重要性，以及将阳光转化为氢的潜力作为一种能源范例。更具体地说，本研究将研究基于蒽和相关单位的超分子支架配体的使用，这些配体支持[Fe]-氢化酶的化学复杂结构。该酶利用低自旋铁(II)-二羰基结合硫代酸酯、吡啶酮和有机金属酰基供体进行H2活化和氢化物转移。提出的研究旨在发现支架中的分子柔韧性如何加速H2的活化和催化。这将通过在支架中安装柔性的“类蒽”（如噻吩和硒）来实现，以便(i)更容易进入应变和反应性基态几何，和/或（ii）降低应变过渡态的能量以加速催化。其次，该研究将致力于将分子铁复合物安装在一个特征明确的蛋白质支架内，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。本研究还旨在合成与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接近铁硫碳化物簇。该项目将利用“历史上的”碳化铁-羰基簇作为硫和硫酸盐结合在新铁模型配合物中的合成子。将探索亲电性（S2Cl2, RS - cl）和亲核性（Na2S, RS -）加成机制，重点是使用碳化铁-羰基簇的不协调版本（非wade - mingos规则）进行反应性硫加成。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.