Hydrogen Bonding Cavity Motifs About Metal Ions

关于金属离子的氢键腔图案

• 批准号: 9978348
• 负责人: Andrew S. Borovik
• 金额: $ 41.33万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9978348
• 关键词: Active Sites; Aging; Architecture; Biological; Catalysis; Characteristics; Chemicals; Dioxygen; Exhibits; Functional disorder; Goals; Health; Human; Hydrogen Bonding; Individual; Instruction; Investigation; Ions; Lead; Ligands; Link; Maintenance; Mediating; Metalloproteins; Metals; Modification; Molecular; Process; Property; Research; Site; Structure; Structure-Activity Relationship; System; Water; catalyst; insight; metalloenzyme; oxidation; structural biology

The broad purpose of the research in this proposal is to understand how microenvironrnents (secondary coordination spheres) about metal ions control function. A bio-inspired synthetic approach is utilized that incorporates principles of molecular architecture found in the active sites of metalloproteins into synthetic systems. Multidentate ligands will be developed that create rigid organic structures around metal ions and place hydrogen bond donors or acceptors proximal to the metal centers, forming specific microenvironments. One distinguishing attribute of these systems is the ability to make site-specific modifications to the structure in order to evaluate correlations between the microenvironment and reactivity. A focus of this research is the examination of transient intermediates that are formed from the activation of dioxygen and the oxidation of water - processes that are directly linked to the maintenance of human health and aging. Long-term goals include developing structure-function relationships in metal-assisted oxidative catalysis. Metalloproteins perform functions not yet achieved in synthetic systems. Our hypothesis is that the lack of control of the secondary coordination sphere in synthetic compounds is a major obstacle in establishing the desired functions. Results from structural biology show that hydrogen bonds within the secondary coordination spheres of metalloproteins are instrumental in regulating function. Therefore, the function and dysfunction of health-related metalloproteins can be understood in the context of changes in their microenvironrnents. However, it is still unclear, even in biomolecules, how non-covalent interactions influence metal-mediated processes. Investigations into these effects require fundamental reactivity and mechanistic studies in which the contributions of single components can be analyzed individually. We have developed synthetic hydrogen bonding systems in which the molecular components that define the structure around the metal ion are specifically controlled; in turn, this permits the formation of systems whose activity can be tailored to a particular function. This ability to regulate the microenvironment allows for systematic studies into structure- function relationships that lead to fundamental understanding of chemical processes. Ultimately, this research will provide insights into the properties of biological catalysts and lead to new classes of synthetic catalysts that exhibit the exquisite control over reactivity that is characteristic of metalloenzymes. RELEVANCE (See instructions): Please see attached.

本提案中研究的广泛目的是了解微环境（二级协调）如何 球）关于金属离子控制功能。采用仿生合成方法，该方法结合了以下原理： 将金属蛋白活性位点中发现的分子结构引入合成系统。多齿配体将是 开发出在金属离子周围创建刚性有机结构并将氢键供体或受体放置在附近 到金属中心，形成特定的微环境。这些系统的一个显着特征是能够 对结构进行特定位点的修改，以评估微环境和 反应性。这项研究的一个重点是检查由激活形成的瞬时中间体 分子氧和水的氧化是与维持人类健康和衰老直接相关的过程。 长期目标包括开发金属辅助氧化催化中的结构-功能关系。 金属蛋白具有合成系统尚未实现的功能。我们的假设是缺乏控制 合成化合物中的二级配位层是建立所需功能的主要障碍。结果 结构生物学表明，金属蛋白二级配位区内的氢键是 起到调节功能的作用。因此，与健康相关的金属蛋白的功能和功能障碍可以通过 并结合其微环境的变化来理解。然而，即使在生物分子中，目前仍不清楚 非共价相互作用影响金属介导的过程。对这些影响的调查需要基础知识 反应性和机理研究，其中可以单独分析单个组分的贡献。我们 开发了合成氢键系统，其中定义结构的分子成分 周围金属离子受到专门控制；反过来，这允许形成其活动可以被 为特定功能量身定制。这种调节微环境的能力允许对结构进行系统研究 函数关系导致对化学过程的基本理解。最终，这项研究将 提供对生物催化剂特性的见解，并导致新型合成催化剂的出现 对金属酶特有的反应性的精确控制。 相关性（参见说明）： 请参阅附件。