Functional Metal-Ligand Assemblies: Structural Switching and Biomimetic Catalysis

在化学系大分子、超分子和纳米化学（MSN）项目的支持下，加州大学河滨分校的Richard J. Hooley教授正在开发新的化学结构，可以模仿酶等大型生物分子的行为。酶可以选择性地在生物系统中进行许多不同的化学反应，反应特异性由“活性位点”结合袋附近官能团的配置来定义。人工化学催化剂在分子合成中有许多用途，但小分子不具备确定的结合袋是生物催化的一个方面。在这个研究项目中，Hooley团队的目标是开发自组装方法，以创造类似于酶的新化学结构，并探索这些结构在催化中的潜在应用。此外，通过将柔性基序结合到上层结构中，催化原则上可以由外部介质控制，从而允许“可切换”仿生催化的发展。该项目将为研究生和本科生提供跨学科的研究培训，涵盖化学、生物学和材料科学领域。快速制造大型复杂分子的一种方法是自组装，即单个分子块可逆地排列成上层结构，上层结构包含一个宽敞的结合袋，允许其他分子进入。自组装笼状配合物具有广泛的应用，但其作为仿生催化剂的使用受到其“活性位点”腔中缺乏活化基团的限制。胡利研究小组试图通过基于金属配体的自组装创造合成受体来弥补这一点，这种受体可以在腔内显示反应性官能团。然后，这些功能化受体可以用作酶模拟催化剂，促进各种复杂的多步骤反应。基于将反应性功能与受体结合的不同策略，本项目侧重于两个广泛的子领域：1)利用包含刚性定位官能团的自组装笼研究大范围的仿生催化；2)利用具有灵活旋转功能的笼型宿主研究可切换的分子识别和催化。在第一个领域，将合成具有一系列内部反应基团的新受体，这些受体可以在不同的介质中发挥作用，以增强催化活性。它们将广泛应用于仿生催化，重点是复杂的多步骤反应。在第二个领域，具有宽敞空腔和可以绕轴自由旋转的官能团的功能化笼将成为目标，并用于由外部效应物控制的触发反应，选择性分子识别和不对称催化。该领域的一个重要目标是确保笼型催化剂在各种反应条件下都是稳定的，并且可以在包括水溶液在内的一系列不同环境中应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Macromolecular, Supramolecular, and Nanochemistry (MSN) Program of the Division of Chemistry, Professor Richard J. Hooley of the University of California–Riverside is developing new chemical structures that can mimic the behavior of large biomolecules such as enzymes. Enzymes can selectively perform many different chemical reactions in the biological systems, with reaction specificity being defined by the disposition of functional groups about the "active site” binding pocket. Artificial chemical catalysts have many uses in molecular synthesis, but a defined binding pocket is one aspect of biological catalysis that small molecules do not possess. In this research project, the Hooley team aims to develop self-assembly approaches to create new chemical structures that act in a manner similar to enzymes and to explore the potential applications of these structures in catalysis. In addition, by incorporating flexible motifs into the superstructure, the catalysis can, in principle, be controlled by external agents, allowing for the development of “switchable” biomimetic catalysis. This project will provide interdisciplinary research training to graduate students and undergraduates in areas that bridge chemistry, biology, and materials science. One approach to creating large, complex molecules in a rapid manner is self-assembly, whereby individual pieces are reversibly arranged to make superstructures that contains a spacious binding pocket which allows other molecules to enter. Self-assembled cage complexes have a wide array of applications, but their use as biomimetic catalysts is limited by the lack of activating groups in their “active site” cavities. The Hooley research group seeks to remedy this by creating synthetic receptors via metal-ligand based self-assembly that display reactive functional groups to their cavity interiors. These functionalized receptors can then be used as enzyme-mimicking catalysts that promote a variety of complex, multi-step reactions. This project focuses on two broad sub-areas, based on the different strategies to incorporate reactive functions to the receptors: 1) Investigate broad-scope biomimetic catalysis with self-assembled cages containing rigidly positioned functional groups; 2) Investigate switchable molecular recognition and catalysis using cage hosts with flexible, rotating functions. In the first Area, new receptors will be synthesized that have a range of internal reactive groups and can function in different media for enhanced catalytic activity. They will be used in broad scope biomimetic catalysis, focusing on complex, multistep reactions. In the second Area, functionalized cages with spacious cavities and functional groups that can rotate freely about an axis will be targeted, and used for triggered reactivity controlled by external effectors, for selective molecular recognition, and for asymmetric catalysis. An important objective in this area is to ensure that the cage catalysts are stable to a variety of reaction conditions, and can be applied across a range of different environments, including in aqueous solution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.