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

将生命规则应用于催化：酶活性位点中扭曲的配位环境的意义

• 批准号: 1904560
• 负责人: Shiyu Zhang
• 金额: $ 44万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904560&HistoricalAwards=false
• 关键词: Applying; Rules; Life; Catalysis; Significance

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.

大自然使用含有一种或多种地球上丰富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，酶的反应性与其合成类似物之间通常存在显着差异，这揭示了控制生命系统中金属离子反应性的微妙规则的存在。凭借该奖项，化学部的生命过程化学项目正在资助俄亥俄州立大学的张世宇博士发现、阐明和应用酶活性位点用于实现困难的细胞反应的基本规则。该研究项目与一项教育计划相结合，其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。该研究项目的重点是结合合成无机和理论方法，了解扭曲的配位环境（生物体金属蛋白活性位点的普遍特征）对反应性的影响。关键概念是由对称有机/有机金属配体支持的仿生催化剂无法充分模拟对于执行生物功能通常很重要的电子结构细节。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畸变的函数而变化。具体来说，该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）亚硝酸盐（NO2-）和一氧化氮（NO）的相互转化，由以铜蓝蛋白（Cp）和亚硝酸铜还原酶（CuNiR）活性位点为模型的铜亚硝酰复合物催化； （2）以颗粒甲烷单加氧酶（pMMO）活性位点为模型的铜氧配合物催化的具有挑战性的 sp3 C-H 羟基化； （3）由位点分化的三铜氧簇催化氧选择性四电子还原成水，该簇以多铜氧化酶（MCO）中的三核铜位点为模型。该研究将利用酶的结构-功能关系，旨在确定重现酶反应性的新策略，并发现催化剂设计的广泛通用规则，这些规则适用于用作灵感的生物系统范围之外。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查进行评估，被认为值得支持。 标准。

项目成果

Multiple Proton-Coupled Electron Transfers at a Tricopper Cluster: Modeling the Reductive Regeneration Process in Multicopper Oxidases

Tricopper 簇上的多个质子耦合电子转移：模拟多铜氧化酶中的还原再生过程

• DOI: 10.1021/jacs.1c10948
• 发表时间: 2022
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Zhang, Weiyao;Moore, Curtis E.;Zhang, Shiyu
• 通讯作者: Zhang, Shiyu

Iron(II/III) Halide Complexes Promote the Interconversion of Nitric Oxide and S -Nitrosothiols through Reversible Fe-S Interaction

铁(II/III)卤化物配合物通过可逆的Fe-S相互作用促进一氧化氮和S-亚硝基硫醇的相互转化

• DOI: 10.1021/acs.inorgchem.1c00203
• 发表时间: 2021
• 期刊: Inorganic Chemistry
• 影响因子: 4.6
• 作者: Poptic, Anna L.;Zhang, Shiyu
• 通讯作者: Zhang, Shiyu

Redox‐Neutral S ‐nitrosation Mediated by a Dicopper Center

二铜中心介导的氧化还原 - 中性 S - 亚硝化

• DOI: 10.1002/anie.202102589
• 发表时间: 2021
• 期刊: Angewandte Chemie International Edition
• 作者: Tao, Wenjie;Moore, Curtis E.;Zhang, Shiyu
• 通讯作者: Zhang, Shiyu