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)计划的支持下，加州大学河滨分校的理查德·J·胡利教授正在开发新的化学结构，可以模拟酶等大生物分子的行为。酶可以选择性地在生物系统中执行许多不同的化学反应，反应的特异性是由活性部位结合口袋周围的官能团的配置来定义的。人工化学催化剂在分子合成中有许多用途，但定义的结合口袋是小分子所不具备的生物催化的一个方面。在这项研究项目中，Hooley团队的目标是开发自组装方法，以创建以类似酶的方式工作的新化学结构，并探索这些结构在催化中的潜在应用。此外，通过在超结构中加入灵活的基序，催化原则上可以由外部试剂控制，从而允许开发“可切换”的仿生催化。该项目将在化学、生物和材料科学领域为研究生和本科生提供跨学科的研究培训。一种快速创造大而复杂的分子的方法是自组装，即单个片段被可逆地排列，以形成包含一个宽敞的结合口袋的超结构，允许其他分子进入。自组装笼状络合物具有广泛的应用前景，但其作为仿生催化剂的应用受到其“活性中心”空穴中活性基团缺乏的限制。Hooley研究小组试图通过基于金属配体的自组装来创造合成受体来补救这一点，这种自组装将反应性官能团显示在空洞内部。然后，这些功能化的受体可以用作模拟酶的催化剂，促进各种复杂的多步骤反应。本项目的重点是两个大的子领域，根据不同的策略将反应功能结合到受体上：1)利用含有刚性定位官能团的自组装笼子研究广泛的仿生催化；2)利用具有灵活、旋转功能的笼子宿主研究可切换的分子识别和催化。在第一个领域，将合成新的受体，这些受体具有一系列内部反应基团，可以在不同的介质中发挥作用，以增强催化活性。它们将用于广泛的仿生催化，重点是复杂的、多步骤的反应。在第二个领域，具有宽敞的空腔和可以绕轴自由旋转的官能化基团的功能化笼子将成为目标，并用于外部效应器控制的触发反应、选择性分子识别和不对称催化。这一领域的一个重要目标是确保笼形催化剂在各种反应条件下都是稳定的，并且可以应用于各种不同的环境，包括在水溶液中。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.