Bioinspired Structure/Function Studies that Leverage Proton-Responsive Secondary Coordination Spheres and Ligand-Based Redox Sites

利用质子响应二级配位球和基于配体的氧化还原位点的仿生结构/功能研究

• 批准号: 10731032
• 负责人: John Gilbertson
• 金额: $ 38.67万
• 依托单位: WESTERN WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731032
• 关键词: Active Sites; Alkalies; Anions; Area; Binding; Binding Sites; Carcinogens; Charge; Chemicals; Classification; Complex; Coupling; Crown Ethers; Data; Development; Electronics; Electrons; Encapsulated; Family; Gastrointestinal tract structure; Health; Human; Hydrogen Bonding; Investigation; Ions; Ligands; Malignant Neoplasms; Measures; Metals; Methemoglobinemia; Modeling; Nitrates; Nitrites; Nitrogen Dioxide; Nitrosamines; Oxidation-Reduction; Oxidoreductase; Pathway interactions; Process; Property; Protons; Public Health; Reaction; Research; Role; Series; Site; Source; Structure; Structure-Activity Relationship; Syndrome; System; Transition Elements; Translating; United States Environmental Protection Agency; Urea; Water Pollutants; World Health Organization; chemical reaction; data reduction; denitrification; drinking water; electric field; ground water; innovation; metallicity; metalloenzyme; novel; oxidation; receptor; scaffold; synthetic construct

Project Summary/Abstract The aim of the research described in this renewal proposal is to continue to develop unique and innovative bioinspired complexes to translate metalloenzyme active site reactivity and selectivity into the realm of synthetic constructs for the study biologically relevant reactions. Many metalloenzymes catalyze reactions that involve either oxidation or reduction of substrate, vital for maintaining human health, and these chemical transformations are generally multi-electron redox processes. One such process is the denitrification of Nitrite (NO2-) and nitrate (NO3-). NO3- and NO2- are known water pollutants and suspected carcinogens, in the case of NO2-. A key step in the denitrification pathway is the N-N bond formation to form N2O. Systems capable of denitrification, and N– N bond-forming reactions in particular, are vital to elucidate the mechanism of N2O formation. We plan to explore key reactions in denitrification through the continued development of bioinspired metal ligand complexes containing secondary coordination spheres capable of enticing anion complexation and merging those with ligand-based redox-active sites within a single metal-ligand construct. We will continue to utilize the redox-active pyridinediimine (PDI) scaffold, as it is possible to uncouple the charge state of the secondary coordination sphere of the complex from the ligand-based redox-active sites. It is possible to independently tune both the structural properties of the metal-ligand scaffolds (secondary coordination sphere) and the redox properties (ligand-based redox active sites) independently. We propose that this approach is an innovative and effective way to model the reactivity of metalloenzymes and provide regulatory control over chemical reactions. A series of structure- function relationships will leverage these novel structural motifs to explore denitrificaiton through NOx- binding and reduction, including N-N coupling to form N2O. These studies will provide a fundamental understanding necessary to provide a blueprint for metal-ligand constructs that can be tuned for denitrification reactions. Ultimately, this research will lead to a new complexes that display the elegant control over reactivity that is inspired by metalloenzymes. Specific Aims include: (1) Develop a class of ditopic H-bond donating receptors for NOx- binding and reduction. (2) Investigate N-N bond formation reactions from NOx- sources. (3) Utilize electric fields in the secondary coordination sphere to entice NOx- reactivity.

项目总结/摘要 本更新提案中所述研究的目的是继续开发独特和创新的 生物启发复合物，将金属酶活性位点的反应性和选择性转化为合成领域 研究生物学相关反应的结构。许多金属酶催化的反应涉及 无论是氧化或还原底物，对维持人体健康至关重要，这些化学转化 通常是多电子氧化还原过程。一个这样的过程是亚硝酸盐（NO2-）和硝酸盐的反硝化 （NO3-）。NO3-和NO2-是已知的水污染物和疑似致癌物，在NO2-的情况下。一个关键步骤 在反硝化途径中，N-N键的形成是N2 O的形成。能够进行脱氮的系统，以及N- 特别是N键形成反应，是至关重要的，以阐明N2 O的形成机制。我们计划探索 通过生物启发的金属配体络合物的持续发展， 含有能够诱导阴离子络合并将它们与 基于配体的氧化还原活性位点在单个金属-配体构建体内。我们将继续利用氧化还原活性 吡啶二亚胺（PDI）支架，因为它可以解偶联二级配位球的电荷状态 从基于配体的氧化还原活性位点的复合物。可以独立地调整结构 金属-配体支架的性质（次级配位球）和氧化还原性质（基于配体的 氧化还原活性位点）。我们认为，这种方法是一种创新的和有效的方式来建模 金属酶的反应性并提供对化学反应的调节控制。一系列的结构- 功能关系将利用这些新的结构基序，探索通过氮氧化物的结合 和还原，包括N-N偶联形成N2 O。这些研究将提供一个基本的理解 有必要提供一个蓝图的金属配体结构，可以调整脱氮反应。 最终，这项研究将导致一种新的复合物，它显示出对反应性的优雅控制， 受到金属酶的启发 具体目标包括： (1)开发一类用于NOx结合和还原的双位H键供体受体。 (2)研究氮氧化物源的N-N键形成反应。 (3)在次级配位领域中利用电场来诱导NOx反应性。