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，其结合了在金属蛋白的活性位点中发现的分子结构的原理。将开发多齿配体，在金属离子周围产生刚性有机结构。这些配体将氢键（H-键）供体或受体置于金属中心附近，形成特定的微环境。这些系统的一个显着属性是，可以很容易地完成结构中的位点特异性调制，以评估与反应性的相关性。这项研究的一个重点是考虑金属络合物的分子氧结合和活化-与维持人类健康和衰老直接相关的过程。长期目标包括发展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圈的控制是欲望功能的主要障碍。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，与健康相关的金属蛋白的功能和功能障碍可以在其微环境变化的背景下理解。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。对这些影响的调查需要基本的反应性和机制研究，其中可以单独分析单个组分的影响。我们已经开发出合成氢键系统，从而获得对定义金属离子周围结构的分子组分的控制;反过来，这允许形成其活性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，这项研究将提供深入了解生物催化剂的性质，并导致新的合成催化剂类别，包括金属酶的反应特性的精致控制。

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. Multidentate ligands will be developed that create rigid organic structures around metal ions. These ligands place hydrogen bond (H-bond) donors or acceptors proximal to the metal centers, forming specific microenvironments. One distinguishing attribute of these systems is that site-specific modulations in structure can be readily accomplished, in order to evaluate correlations with reactivity. A focus of this research is consideration of dioxygen binding and activation by metal complexes - processes linked directly 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 to desire functions. Results from structural biology show that H-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. It is still unclear, even in biomolecules, how non-covalent interactions are able to influence metal-mediated processes. Investigations into these effects require basic reactivity and mechanistic studies in which the effects of single components can be analyzed individually. We have developed synthetic H-bonding systems whereby control of the molecular components that define the structure around the metal ion is obtained; 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 incorporate the exquisite control of reactivity characteristic of metalloenzymes.