Foldamer Heterosequences: A Modular Approach to Customizable Molecular Containers

本研究的重点是开发一种方法，以模块化的方式使用异序列来定制来自构象有序低聚物的分子隔间内的空间。将开发统计计算机辅助设计（SCAD）算法，以帮助合理设计这些隔间内的体积要求和凹表面，以补充特定的客人，中间或过渡状态。本文将改进制备低聚苯乙炔（PE）异序列的方法，并探索新的构建块，以使折叠PE异序列形成的隔室的大小、形状和内部功能化多样化。将制备经SCAD鉴定的优化序列，并测量与N，N'-二苯基哌嗪的结合亲和力，并与一组预测对该配体具有低亲和力的异构体对照序列进行比较。在这些发展的基础上，提出了催化反应筛分的概念，作为实现基于尺寸的活性底物选择性活化的手段。通过这个奖项，有机和大分子化学项目支持伊利诺伊大学厄巴纳-香槟分校化学系的杰弗里·s·摩尔博士和宾夕法尼亚大学化学系的杰弗里·g·萨文博士的研究。这一合作努力将集中在构建寡聚序列的方法的发展，将折叠成纳米级容器。这种方法在理论和实验的指导下，将允许在分子隔间内产生定制的空间，这反过来将带来特定的分子识别，最终达到控制化学反应性的目的。该项目具有理论与实验相结合的广泛影响，从而为本科生、研究生和博士后的多学科培训提供了良好的环境。

The focus of this research is the development of methodology for the use of heterosequences in a modular way to customize the space inside molecular compartments derived from conformationally ordered oligomers. Statistical computer aided design (SCAD) algorithms will be developed to help rationally design both the volume requirements and concave surfaces inside these compartments complementary to a particular guest, intermediate or transition state of interest. Improved methods for the preparation of oligomeric phenylene ethynylene (PE) heterosequences will be developed and new building blocks will be explored in order to diversify the size, shape and internal functionalization of compartments created by folded PE heterosequences. Optimized sequences identified by SCAD will be prepared and binding affinity to N,N'-diphenylpiperazines will be measured and compared to a set of isomeric control sequences predicted to have low affinity for this ligand. Building on these developments, the concept of catalytic reactive sieving is proposed as a means to achieve size-based selective activation of reactive substrates. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Jeffrey S. Moore of the Department of Chemistry at the University of Illinois at Urbana-Champaign and Dr. Jeffrey G. Saven of the Department of Chemistry at the University of Pennsylvania. This collaborative effort will focus on the development of methodology for the construction oligomeric sequences that will fold into nanoscale containers. This approach, guided by theory and experiment, will allow the production of a customized space inside a molecular compartment and this, in turn will bring about specific molecular recognition for the eventual purpose of controlling chemical reactivity. The project has the broader impact of integrating activities in both theory and experimentation thus providing an excellent setting for the multidisciplinary training of undergraduate, graduate and postdoctoral students.