Hydrogen Bonding Cavity Motifs About Metal Ions

这项建议中研究的广泛目的是了解微环境(次级协调 球体)关于金属离子的控制功能。利用了一种受生物启发的合成方法，它结合了 在金属蛋白的活性部位发现的分子结构进入合成系统。多齿配体将是 在金属离子周围形成刚性有机结构，并将氢键供体或受体放置在近端 到金属中心，形成特定的微环境。这些系统的一个显著特征是能够 对结构进行特定部位的修改，以评估微环境和 反应性。这项研究的一个重点是检查由活化形成的瞬时中间体 氧气和水的氧化--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。 金属蛋白具有合成系统中尚未实现的功能。我们的假设是，缺乏对 合成化合物中的二次配位球是建立所需功能的主要障碍。结果 来自结构生物学的研究表明，金属蛋白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 在其微环境变化的背景下理解。然而，即使在生物分子中，也仍然不清楚如何 非共价相互作用影响金属介导的过程。对这些影响的调查需要从根本上 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成分 在金属离子周围被特别控制；反过来，这允许形成其活性可以被 为特定的功能量身定做的。这种调节微环境的能力允许对结构进行系统研究- 导致对化学过程的基本理解的功能关系。最终，这项研究将 提供对生物催化剂的特性的见解，并导致显示出 对反应性的精细控制，这是金属酶的特点。 相关性(请参阅说明)： 请见附件。

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.