Hydrogen Bonding Cavity Motifs About Metal Ions

 描述（由申请人提供）：本提案中研究的广泛目的是了解金属离子控制功能的微环境（次级配位球）。利用生物启发的合成方法，将金属蛋白活性位点中发现的分子结构原理结合到合成系统中。将开发多齿配体，在金属离子周围产生刚性有机结构，并将氢键供体或受体靠近金属中心，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位点特异性修改，以评估微环境和反应性之间的相关性。这项研究的一个重点是检查由分子氧的活化和水的氧化形成的瞬态中间体-这些过程与维持人类健康和衰老直接相关。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，在合成化合物中缺乏对次级配位球的控制是建立所需功能的主要障碍。结构生物学的结果表明，金属蛋白的二级配位球内的氢键有助于调节功能。因此，可以在其微环境变化的背景下理解与健康相关的金属蛋白的功能和功能障碍。然而，即使在生物分子中，非共价相互作用如何影响金属介导的过程仍然不清楚。这些影响的调查需要基本的反应性和机制的研究，其中单个组件的贡献可以单独分析。我们已经开发了合成氢键系统，其中定义金属离子周围结构的分子组分受到特定控制;反过来，这允许形成 其活动可以根据特定功能定制的系统。这种调节微环境的能力允许系统地研究结构-功能关系，从而对化学过程有基本的了解。最终，这项研究将提供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，这些催化剂表现出对反应性的精细控制，这是金属酶的特征。

 DESCRIPTION (provided by applicant): The broad purpose of the research in this proposal is to understand how microenvironments (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 microenvironments. 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.