Hydrogen Bonding Cavity Motifs About Metal Ions

描述（由申请人提供）：本提案研究的主要目的是了解金属离子控制的微环境（次级配位球）如何起作用。利用生物启发合成方法，结合在金属蛋白活性位点发现的分子结构原理。多齿配体将在金属离子周围形成刚性有机结构。这些配体将氢键（h键）供体或受体放置在靠近金属中心的位置，形成特定的微环境。这些系统的一个显著特征是，可以很容易地完成特定位点的结构调制，以便评估与反应性的相关性。本研究的一个重点是考虑双氧结合和金属配合物的激活-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。金属蛋白具有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二级配位球的控制是欲望功能的主要障碍。结构生物学结果表明，金属蛋白二级配位球内的氢键在调节功能中起重要作用。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能够影响金属介导的过程仍不清楚。对这些影响的调查需要基本的反应性和机理研究，其中单个组分的影响可以单独分析。我们已经开发了合成氢键系统，通过这种系统可以控制定义金属离子周围结构的分子成分；反过来，这允许系统的形成，其活动可以被定制为特定的功能。这种调节微环境的能力允许系统地研究结构-功能关系，从而导致对化学过程的基本理解。最终，这项研究将为生物催化剂的特性提供新的见解，并导致新型的合成催化剂，这些催化剂结合了对金属酶反应性特征的精细控制。

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.