New Foldamer Catalysts

在化学系的大分子、超分子和纳米化学项目的支持下，塞缪尔·H。威斯康星大学麦迪逊分校的盖尔曼将开发折叠体催化剂，其灵感来自酶的结构多样性。 酶是基于蛋白质的大分子，通过加速生物体中的许多化学反应来充当生物催化剂。 酶催化的一些最著名的反应包括蔗糖转化为葡萄糖和果糖，葡萄糖分解为乙醇和二氧化碳，以及脂肪水解。 另一方面，折叠体是模拟蛋白质样构象行为的非天然支架，也可能是酶的催化性质。在这个项目中，除了天然肽的常用α-氨基酸结构单元外，还将使用β-氨基酸制备折叠体。 在蛋白质折叠过程中，关键的亚基被排列成精确的三维阵列，这对于与其他分子结合和催化化学反应至关重要。 在这个项目中，有机和超分子化学专门定制，使有效的功能团纳入螺旋foldamer支架将被用来制备双功能和三功能foldamer催化剂。 然后将合成的催化剂用于各种金属和非金属催化的碳-碳键形成反应。 该项目将提供跨学科研究的优秀培训，使年轻学者能够在学术界，工业界或其他环境中从事富有成效的职业。 此外，Gellman教授将继续通过参与研究生招生和担任Gordon Research Conferences的受托人来支持科学界的多样性、公平性和包容性的扩大。该项目将通过研究含有新型活性二联体的α/β-肽来寻求扩大双功能折叠体催化的范围。 在第一个总目标下，将采取三种途径，重点是双功能催化。 在第一种途径中，将含有新型反应性基团的侧链并入折叠体支架中，所述新型反应性基团通过底物的共价活化起作用，具体地，用于α-取代的烯醛的亲电活化的酰肼，以及用于朝向Stetter反应活化醛的噻唑鎓系统或相关杂环。 在第二种途径中，将探索旨在通过H-键合或阳离子-π-相互作用非共价地活化底物的侧链。 第三条途径将集中于添加联吡啶或三联吡啶单元，其将用于与镍络合以及随后的醛的α-芳基化。在第二个目标中，该团队将寻求利用折叠体支架的模块化，以允许三个功能组协调工作，以促进单一的转化。该项目旨在开发受酶结构多样性启发的新催化剂。 精确控制折叠体内多个反应位点位置的能力可以为使用这些酶模拟物进行协同催化提供令人兴奋的机会。该奖项反映了NSF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 the support of the Macromolecular, Supramolecular and Nanochemistry program in the Division of Chemistry, Professor Samuel H. Gellman of the University of Wisconsin-Madison will develop foldamer catalysts that are inspired by the structural diversity of enzymes. Enzymes are large protein-based macromolecules that act as biological catalysts by accelerating numerous chemical reactions in living organisms. Some of the most well known reactions catalyzed by enzymes include conversion of cane sugar into glucose and fructose, breaking of glucose into ethyl alcohol and carbon dioxide, and hydrolysis of fats. Foldamers, on the other hand, are unnatural scaffolds that mimic protein-like conformational behavior and potentially also the catalytic properties of enzymes. In this project, foldamers will be prepared using β-amino acids in addition to the usual α-amino acid building blocks for natural peptides. During the protein folding process, key subunits are arranged into the precise three-dimensional arrays that are essential for binding to other molecules and catalyzing chemical reactions. In this project, organic and supramolecular chemistries specifically tailored to enable efficient functional group incorporation into helical foldamer scaffolds will be utilized to prepare bifunctional and trifunctional foldamer catalysts. The synthesized catalysts will then be utilized in variety of metal and non-metal catalyzed carbon-carbon bond forming reactions. This project will provide excellent training in interdisciplinary research and enable young scholars to undertake productive careers in academia, industry, or other settings. Additionally, Professor Gellman will continue to support expansion of diversity, equity, and inclusion in the scientific community through his involvement in graduate student recruitment and through his activities as a Trustee of the Gordon Research Conferences.This project will seek to expand the range of bifunctional foldamer catalysis by examining α/β-peptides containing new types of reactive diads. Three paths will be pursued under the first general goal, focusing on bifunctional catalysis. In the first path, side chains containing new types of reactive groups that function via covalent activation of substrates, specifically, hydrazides for electrophilic activation of α-substituted enals, and thiazolium systems or related heterocycles for activation of aldehydes toward Stetter reactions, will be incorporated into foldamer scaffolds. In the second path, side chains intended to activate substrates noncovalently either through H-bonding or cation-π-interactions will be explored. The third path will focus on adding bipyridine or terpyridine units that will be used for complexation with nickel and subsequently α-arylation of aldehydes. In the second goal, the team will seek to harness the modularity of foldamer scaffolds to allow three functional groups to work in coordination to promote a single transformation. This project seeks to enable the development of new catalysts that are inspired by the structural diversity of enzymes. The ability to precisely control the location of multiple reactive sites within foldamers could additionally provide exciting opportunities of using these enzyme mimics for synergistic catalysis.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.