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

自然界利用含有一种或多种富含地球的金属的酶作为催化剂，在环境条件下完成具有挑战性的反应。位于这些酶活性中心的金属离子的配位环境往往是新的合成催化剂的灵感来源。然而，酶的反应性与其合成类似物之间往往存在显著的差异，这揭示了管理生命系统中金属离子的反应性的微妙规则的存在。化学部生命过程化学项目将资助俄亥俄州立大学的张世宇博士发现、阐明和应用酶活性部位用于实现复杂细胞反应的基本规则。该研究项目与一个教育项目相结合，该项目的目标是教会学生如何让社区成员参与现代STEM研究，并通过协作外展活动提高科学素养。研究项目重点是利用合成无机和理论方法相结合的方法，了解扭曲的配位环境-活生物体中金属蛋白活性中心的普遍特征-对反应活性的影响。关键的概念是，由对称的有机/有机金属配体支撑的生物启发催化剂不能充分模拟经常对执行生物功能重要的电子结构细节。该研究项目的重点是了解合成模型络合物的反应性如何作为几何扭曲的函数变化。具体地说，这项研究将评估由蛋白质活性中心激发的扭曲的配位环境对以下方面的影响：(1)模拟铜蓝蛋白(CP)和亚硝酸铜还原酶(CuNiR)活性中心的亚硝酰铜配合物催化亚硝酸根(NO2-)和一氧化氮(NO)的相互转化；(2)模拟颗粒甲烷单加氧酶(PMMO)活性中心的铜-氧配合物催化具有挑战性的SP3 C-H羟基化；(3)模拟铜氧化物(MCO)中三核铜中心的位置差异化的多氧铜原子簇催化氧的选择性四电子还原为水。这项研究将利用酶的结构-功能关系，旨在确定复制酶的反应性的新策略，并发现可广泛推广的催化剂设计规则，这些规则适用于作为灵感的生物系统的范围。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。

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.