TRIPOD LIGANDS FOR ENZYME MODELS AND ANION COMPLEXATION

用于酶模型和阴离子络合的三脚架配体

• 批准号: 2183993
• 负责人: GERARD PARKIN
• 金额: $ 17.62万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2183993
• 关键词: X ray crystallography; active sites; anions; carbonate dehydratase; chemical structure function; chemical synthesis; enzyme model; enzyme substrate complex; ligands; metalloenzyme; nuclear magnetic resonance spectroscopy; receptor binding; stereochemistry; thermodynamics

The role of coordination chemistry in biological systems, ranging from the traditional coordination chemistry of cations, to the host-guest chemistry of anions and neutral molecules, can not be understated. Important examples of coordination and host-guest chemistry in biological systems can be observed in the catalytic properties associated with metal ions in metalloenzymes, the base-pairing of nucleic acids, and the interaction of enzymes with substrates. In view of the complexity of biological systems, studies on smaller synthetic model systems may be used to provide key information in order to elucidate many fundamental biological processes. The thrust of this proposal is to develop some new model systems that will generate important information regarding the roles of both cationic and anionic species in biological systems. Specific goals include (i) introduction of a modified ligand systems for establishing well-defined structural and chemical models for carbonic anhydrase, an important enzyme with respect to aspects of respiration and intracellular CO2/HCO3- equilibration, and (ii) the synthesis and applications of series of new low-coordinate tripodal receptor systems that are designed to bind strongly, but to only one face of an anionic substrate. The aims of this research will be achieved by a combination of solution and solid-state studies. Single crystal X-ray diffraction will be used to determine coordination environments of the metalloenzyme models and also the detailed nature of the host-guest interaction in the solid state. 1H, 13C and 17O NMR spectroscopy will provide further characterization of the metalloenzyme models and also a means for measuring kinetic and thermodynamic parameters. A variety of spectroscopic techniques (e.g. 35C1 NMR spectroscopy) will be used to determine association constants and the strength of the host-guest interaction. Standard chemical techniques will be utilized to investigate applications of these receptor systems in areas such as chiral resolution and phase transfer catalysis.

配位化学在生物系统中的作用，包括 传统的阳离子配位化学，主客体 阴离子和中性分子的化学性质，不可低估。 生物中配位和主客体化学的重要例子 可以在与金属相关的催化性能中观察到系统 金属酶中的离子、核酸的碱基配对以及 酶与底物的相互作用。 鉴于复杂性 生物系统，对较小的合成模型系统的研究可能是 用于提供关键信息以阐明许多基本原理 生物过程。 该提案的主旨是开发一些新的 模型系统将生成有关的重要信息 阳离子和阴离子物种在生物系统中的作用。 具体目标包括 (i) 引入改良的配体系统 建立明确的碳结构和化学模型 脱水酶，一种与呼吸和呼吸有关的重要酶 细胞内 CO2/HCO3- 平衡，以及 (ii) 合成和 系列新型低坐标三足受体系统的应用 旨在牢固结合，但仅与阴离子的一个面结合 基材。 本研究的目标将通过组合来实现 溶液和固态研究。 单晶X射线衍射 将用于确定金属酶的配位环境 模型以及主客交互的详细性质 固态。 1H、13C和17O NMR光谱将提供进一步的信息 金属酶模型的表征以及一种方法 测量动力学和热力学参数。 各种 光谱技术（例如 35C1 NMR 光谱）将用于 确定关联常数和主客体强度 相互作用。 将利用标准化学技术 研究这些受体系统在以下领域的应用 手性拆分和相转移催化。