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.

大自然在环境条件下使用含有一种或多种含有地球的金属的催化剂酶实现了挑战性的反应。这些酶的活性位点中的金属离子的协调环境通常是新合成催化剂的灵感。但是，酶的反应性及其合成类似物的反应性通常存在显着差异，这揭示了控制金属离子在生物系统中反应性的微妙规则。有了这一奖项，化学司的化学过程计划是为俄亥俄州立大学的Shiyu Zhang博士提供资金，以发现，阐明和应用基本规则，使酶主动地点采用活性地点来实现困难的蜂窝反应。该研究项目与一个教育计划融为一体，该计划的目标是教学学生如何使社区成员参与现代STEM研究，并通过协作外展活动提高科学素养。该研究项目专注于理解扭曲的配位环境的影响 - 对生物中的金属蛋白中活性位点无处不在的活性位点在活物质中的反应率 - 对构成方法的组合和构想的组合构成了构成的构成效果。关键概念是，由对称有机/有机金属配体支持的生物启发的催化剂无法充分对通常对于执行生物学功能很重要的电子结构细节进行建模。研究项目着重于了解合成模型复合物的反应性如何随几何变形的函数而变化。具体而言，该研究将评估受蛋白质活性位点启发的扭曲配位环境的影响：（1）亚硝酸盐（NO2-）和硝酸氧化物（NO）的相互转换是由铜氮基络合物催化的，以铜含量（CP）和Copper nitrite Reductase（CP）和铜素（CP）和铜的活性位点模型而建立了模型。 （2）具有挑战性的SP3 C-H羟基化，由以颗粒甲烷单加氧酶（PMMO）的活性位点建模的铜氧化物催化； （3）选择性的四电子还原为由多磷酸氧化酶（MCO）中三核铜位点建模的位点差异的三角体 - 氧气簇催化的水还原为水。这项研究将利用酶的结构功能关系，并将致力于识别新策略来重现酶的反应性，并发现发现广泛的催化剂设计规则，这些规则适用于生物系统的范围之外，该奖项被用作灵感的范围。这些奖项通过NSF的范围进行了反映，反映了NSF的范围及其在范围内的范围。 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