Functional Metal-Ligand Assemblies: Molecular Recognition and Biomimetic Catalysis

加州大学河滨分校的Richard J. Hooley教授得到了化学系大分子、超分子、纳米化学（MSN）和化学催化（CAT）项目的支持，致力于开发自组装方法，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。像酶（一种蛋白质）这样的大型生物分子控制着许多细胞过程，化学家们努力用人工类似物模拟它们的行为，但这些模拟物无法达到天然酶的复杂性。快速制造大型复杂分子的一种方法是自组装，即个体碎片可逆地排列成上层结构。该项目旨在开发自组装方法，以创建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。该项目为化学、生物学和材料科学领域的研究生和本科生提供跨学科研究培训。在开展该项目的过程中，研究成果被纳入化学课程，并开发了新的课程，重点是促进STEM领域的多样性和提高学生的保留率。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”空腔中缺乏活化基团的限制。该项目试图通过基于金属配体的自组装创造合成受体来解决这个问题，这些受体可以在其腔内部显示反应性官能团。本项目侧重于三个具体领域：1)具有内部定向酸性、碱性和/或两亲性基团的新型自组装笼状配合物的创建和主客性质；2)这些笼作为酶模拟催化剂的应用，重点关注小分子催化剂无法实现的新反应模式，如氧碳离子环化中的不寻常立体化学和顺序串联催化；3)通过可逆笼的组装后反应制备出强大的共价笼催化剂，并研究了它们在蛋白酶模拟反应中的功能。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，并且可以在多种不同的环境中应用，包括水溶液。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。

Professor Richard J. Hooley of the University of California-Riverside is supported by the Macromolecular, Supramolecular, and Nanochemistry (MSN) and the Chemical Catalysis (CAT) Programs of the Division of Chemistry to develop self-assembly approaches to creating new chemical structures that act in a manner similar to enzymes and to explore the potential applications of these structures in catalysis. Large biomolecules such as enzymes (a type of protein) control many cellular processes, and chemists strive to mimic their behavior with artificial analogs, but these mimics cannot approach the complexity of natural enzymes. One approach to create large, complex molecules in a rapid manner is self-assembly, whereby individual pieces are reversibly arranged to make superstructures. This project 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. This project provides interdisciplinary research training to a diverse group of graduate and undergraduates students in areas that bridge chemistry, biology and materials science. In the course of conducting this project, research results are incorporated in the chemistry curriculum and new courses are developed with a focus on promoting diversity and increasing retention of students in STEM fields.Self-assembled cage complexes have a wide array of applications, but their use as biomimetic catalysts is constrained by the lack of activating groups in their “active site” cavities. This project seeks to remedy this by creating synthetic receptors via metal-ligand based self-assembly that display reactive functional groups to their cavity interiors. This project focuses on three specific areas: 1) creation and host:guest properties of new self-assembled cage complexes with internally oriented acidic, basic and/or ambiphilic groups; 2) application of these cages as enzyme-mimicking catalysts, focusing on novel reactivity patterns that are not accessible with small molecule catalysts such as unusual stereochemistry in oxocarbenium ion cyclizations, and sequential tandem catalysis; 3) creation of robust covalent cage catalysts via post-assembly reaction of the reversible cages and the study of their function in protease-mimicking reactivity. 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 in multiple different environments, including 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.