Applying Rules of Life to Catalysis: Significance of Distorted Coordination Environments in Enzyme Active Sites

大自然在环境条件下完成具有挑战性的反应，使用含有一种或多种地球丰富金属的酶作为催化剂。位于这些酶活性位点的金属离子的配位环境通常是新合成催化剂的灵感来源。然而，酶和它们的合成类似物的反应性之间往往存在显着差异，这揭示了生命系统中金属离子反应性的微妙规则的存在。有了这个奖项，化学部的生命过程化学项目将资助来自俄亥俄州州立大学的Shiyu Zhang博士，以发现、阐明和应用酶活性位点用于实现困难细胞反应的基本规则。该研究项目与一个教育计划相结合，其目标是教学生如何让社区成员参与现代STEM研究，并通过合作推广活动提高科学素养。该研究项目的重点是了解扭曲的协调环境的影响-活生物体中金属蛋白活性位点的普遍特征-使用合成无机和理论方法相结合的反应性。关键的概念是，由对称有机/有机金属配体支持的生物启发催化剂不能充分模拟电子结构细节，这些细节对于执行生物功能通常是重要的。该研究项目的重点是了解合成模型复合物的反应性如何随着几何变形而变化。具体而言，本研究将评估受蛋白质活性位点启发的扭曲配位环境对以下方面的影响：（1）亚硝酰铜复合物催化的亚硝酸根（NO2-）和一氧化氮（NO）的相互转化，该复合物模拟铜蓝蛋白（Cp）和亚硝酸铜还原酶（CuNiR）的活性位点;（2）模拟颗粒甲烷单加氧酶（pMMO）活性中心的铜氧配合物催化的sp3 C-H羟基化反应;（3）以多铜氧化酶（MCO）中的三核铜位为模型，通过位差三铜氧簇催化氧的选择性四电子还原为水。该研究将利用结构-酶的功能关系，并将致力于确定新的策略，以重现酶的反应性和发现广泛的通用规则，用于催化剂设计，适用于作为灵感的生物系统以外的范围。该奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准。

Nature accomplishes challenging reactions under ambient conditions using as catalysts enzymes that contain one or more Earth-abundant metals. The coordination environment of the metal ions situated in these enzymes' active sites are often an inspiration for new synthetic catalysts. However, there is often a significant difference between the reactivity of enzymes and their synthetic analogs, which reveals the existence of subtle rules that govern the reactivity of the metal ions in living systems. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Shiyu Zhang from The Ohio State University to discover, elucidate, and apply fundamental rules that enzymes active sites employ to achieve difficult cellular reactions. The research project is integrated with an educational program whose goal is to teach students how to engage members of the community in modern STEM research and to improve scientific literacy through collaborative outreach activities.The research project focuses on understanding the impact of distorted coordination environments - a ubiquitous feature of active sites in metalloproteins in living organisms - on the reactivity using a combination of synthetic inorganic and theoretical methods. The key concept is that bioinspired catalysts supported by symmetric organic/organometallic ligands cannot sufficiently model the electronic structure details that are frequently important for executing biological functions. The research project focuses on understanding how the reactivity of synthetic model complexes changes as a function of geometric distortion. Specifically, the research will evaluate the effect of distorted coordination environments inspired by protein active sites on: (1) the interconversion of nitrite (NO2-) and nitric oxide (NO) catalyzed by a copper nitrosyl complex modelled after the active site of ceruloplasmin (Cp) and copper nitrite reductase (CuNiR); (2) the challenging sp3 C-H hydroxylation catalyzed by copper-oxo complexes modeled after the active site of particulate methane monooxygenase (pMMO); (3) selective four-electron reduction of oxygen to water catalyzed by a site-differentiated tricopper-oxo cluster modelled after the trinuclear copper site in multicopper oxidase (MCO). The study will exploit structure-function relationships of enzymes and will be directed towards the identification of new strategies to reproduce the reactivity of enzymes and the discovery of broadly generalizable rules for catalyst design that are applicable beyond the scope of the biological systems used as inspiration.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.