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.

该提案中该研究的广泛目的是了解微观环境如何（次要协调 球体）关于金属离子控制功能。采用了一种生物启发的合成方法，该方法结合了 在金属蛋白的活性位点发现的分子结构成合成系统。多齿配体将是 开发可在金属离子周围创建刚性有机结构，并放置氢键供体或受体近端 到金属中心，形成特定的微环境。这些系统的一个区别属性是能够 对结构进行特定地点的修改，以评估微环境与 反应性。这项研究的重点是对瞬态中间体的检查，这些中间体是由激活形成的 与维持人类健康和衰老直接相关的水过程的二恶英和氧化。 长期目标包括在金属辅助氧化催化中发展结构功能关系。 金属蛋白在合成系统中尚未实现的功能。我们的假设是缺乏对 合成化合物中的次级配位球是建立所需功能的主要障碍。结果 从结构生物学中表明，金属蛋白的二级配位球内的氢键是 在调节功能方面发挥作用。因此，与健康相关金属蛋白的功能和功能障碍可以是 在其微环体变化的背景下理解。但是，即使在生物分子中，也尚不清楚 非共价相互作用会影响金属介导的过程。对这些效果的调查需要基本 可以单独分析单个组件的贡献的反应性和机理研究。我们 已经开发了合成氢键系统，其中分子成分定义结构 金属离子周围得到了特异性控制；反过来，这允许形成活动的系统 根据特定功能量身定制。这种调节微环境的能力允许系统地研究结构 - 导致对化学过程的基本理解的功能关系。最终，这项研究将 提供有关生物催化剂的特性的见解，并导致新的合成催化剂表现出来 对反应性的精致控制，这是金属酶的特征。 相关性（请参阅说明）： 请参阅附件。