Hydrogen Bonding Cavity Motifs About Metal Ions

本提案中研究的广泛目的是了解微观协调（次级协调） 球体）关于金属离子控制功能。利用生物启发的合成方法，其结合了以下原理： 分子结构中发现的活性位点的金属蛋白合成系统。多齿配体将是 开发了一种在金属离子周围产生刚性有机结构，并将氢键供体或受体放置在邻近 形成特定的微环境。这些系统的一个显著属性是能够 对结构进行特定地点的修改，以评估微环境与 反应性这项研究的一个重点是检查由激活的瞬时中间体， 分子氧和水的氧化-这些过程直接关系到人类健康和衰老的维持。 长期目标包括开发金属辅助氧化催化的结构-功能关系。 金属蛋白质具有在合成系统中尚未实现的功能。我们的假设是，缺乏控制的 合成化合物中的次级配位圈是建立所需功能的主要障碍。结果 结构生物学的研究表明，金属蛋白质二级配位球内的氢键是 有助于调节功能。因此，与健康相关的金属蛋白的功能和功能障碍可以通过以下方式来实现： 在其微观结构变化的背景下理解。然而，即使在生物分子中， 非共价相互作用影响金属介导的过程。对这些影响的研究需要基本的 反应性和机理研究，其中单个组分的贡献可以单独分析。我们 已经开发出合成氢键系统，其中定义结构的分子组分 周围的金属离子是专门控制的;反过来，这允许系统的活动，可以形成 为特定的功能量身定制。这种调节微环境的能力允许系统地研究结构- 功能关系，导致化学过程的基本理解。最终，这项研究将 提供了对生物催化剂性质的深入了解，并导致新的合成催化剂类别， 对金属酶特有的反应性的精确控制。 相关性（参见说明）： 请参见附件。

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.