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.

项目概要/摘要 本更新提案中描述的研究目的是继续开发独特和创新的 仿生复合物将金属酶活性位点反应性和选择性转化为合成领域 用于研究生物学相关反应的构建体许多金属酶催化涉及的反应。 对于维持人类健康至关重要的底物的氧化或还原，以及这些化学转化 通常是多电子氧化还原过程，其中一种过程是亚硝酸盐 (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，其中NO2-是关键一步。 在反硝化途径中，N-N键形成，形成能够反硝化的N2O系统，以及N-。 特别是 N 键形成反应对于阐明 N2O 形成机制至关重要。 通过持续开发仿生金属配体配合物来实现反硝化的关键反应 含有能够吸引阴离子络合并将那些与 单一金属配体结构中基于配体的氧化还原活性位点我们将继续利用氧化还原活性位点。 吡啶二亚胺 (PDI) 支架，因为可以解偶联二级配位球的电荷状态 可以独立地调整两个结构。 金属配体支架的性质（二级配位球）和氧化还原性质（基于配体的 我们认为这种方法是一种创新且有效的建模方法。 金属酶的反应性并提供对化学反应的调节控制。 功能关系将利用这些新颖的结构基序来探索通过氮氧化物结合的反硝化 和还原，包括 N-N 耦合形成 N2O，这些研究将提供基本的理解。 为可以调整反硝化反应的金属配体结构提供蓝图是必要的。 最终，这项研究将产生一种新的复合物，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结合和还原的二位氢键供体受体。 (2) 研究 NOx 源的 N-N 键形成反应。 (3)利用次级配位层中的电场来诱导NOx反应。