Perfecting Complex Assemblies of Covalent and Supramolecular Polymers via Biological Principles

生物大分子，如蛋白质、核酸、碳水化合物及其与脂类的偶联物是自然界产生的最常见的组成部分。它们的性质是由它们的原子在结构和复杂组合中的完美排列决定的。尽管它们在我们的日常生活和许多健康、国防和其他技术应用中广泛使用，但合成聚合物的性能无法与金属和生物大分子相匹配。本研究项目旨在将生物学原理应用于聚合物及其复杂组件的构建，将合成聚合物的结构精度提高到金属和天然大分子的水平，并将其在日常生活中的应用扩展到生物系统中遇到的精度和复杂性。该项目涉及设计、合成和表征各种复杂组装的大分子，然后研究它们的结构和性质。该项目将为高中生、本科生、研究生和博士后（包括少数民族）提供跨学科教育，涵盖有机、聚合物、超分子合成、催化、物理学、生物学、合成生物学、纳米科学、纳米医学和超级计算等学科。小组成员将在PI和宾夕法尼亚大学的同事的实验室工作，与美国和国外的科学家合作，并与工业界互动。从这个项目中获得的原则和经验教训将适用于科学、工业和社会复杂系统。由金属原子和大型生物大分子产生的复杂组件在概念上截然不同，但在结构完善和功能上却具有非凡的一致性。合成的共价和超分子聚合物具有统计链长分布、手性、组成和序列。因此，它们不能提供无机和生物组件的结构完善和性能水平。该项目将使用单分散、同手性和序列定义的组分来阐明生产非共价超分子和共价聚合物所需的原理，这些聚合物将自组织成复杂的组装体，展示无机和生物组装体的精度。本文将研究以下主题：(1)阐明Frank-Kasper相的自组织原理；这种现象见于金属、金属合金、某些气体、脂质甚至某些病毒中，最近也见于分子量分布较窄的聚合物、单分散聚合物组分和超分子聚合物中。与它们的超分子定向记忆相一起，弗兰克-卡斯珀相将首次提供生物精度的途径。(2)研究并阐明齿状双螺旋、帽状去消旋和“刚性”立体角烟草花叶病毒样超分子螺旋聚合伴去消旋的普遍性。它们将提供具有生物精度甚至更高的同手性组装体，其中包含通过去消酰基化获得的序列定义和单分散组分。(3)对非迭代法合成单分散类生物聚合物的自中断活性聚合的范围和局限性进行了研究和阐明。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，认为值得支持。

PART 1: NON-TECHNICAL SUMMARYBiological macromolecules such as proteins, nucleic acids, carbohydrates and their conjugates to lipids are the most common building blocks produced by nature. Their properties are determined by a perfect arrangement of their atoms in their structure and in their complex assemblies. Even though they are pervasively used in our daily lives and in many health, defense and other technological applications, synthetic polymers are not able to match the properties of metals and biological macromolecules. This research program aims to use biological principles in the construction of polymers and their complex assemblies to increase the level of structural precision of synthetic polymers to that of metals and natural macromolecules and expand their applications in daily life to the precision and sophistication encountered in biological systems. The project involves design, synthesis, and characterization of macromolecules to a variety of complex assemblies, followed by study of their structure and properties. This project will provide interdisciplinary education for high school, undergraduate, graduate students and postdocs, including minorities, at the interface of disciplines including organic, polymer, supramolecular synthesis, catalysis, physics, biology, synthetic biology, nanoscience, nanomedicine, and supercomputing. Group members will work in the laboratories of the PI and colleagues at Penn, collaborated with scientists in the US and abroad, and interact with industry. The principles and lessons learned from this project will be applicable to scientific, industrial and societal complex systems.PART 2: TECHNICAL SUMMARY Complex assemblies generated from metal atoms and from large biological macromolecules are strikingly dissimilar as concepts but identical in their extraordinary level of structural perfection and functions. Synthetic covalent and supramolecular polymers have statistical chain length distribution, chirality, composition and sequence. Therefore, they cannot provide the level of structural perfection and properties of inorganic and biological assemblies. This project will use monodisperse, homochiral and sequence-defined components to elucidate principles required to produce noncovalent-supramolecular and covalent polymers that will self-organize into complex assemblies exhibiting the precision of inorganic and biological assemblies. The following topics will be investigated: (1) The principles of self-organization of Frank-Kasper phases will be elucidated; these are seen in metals, metal alloys, some gases, lipids and even in some viruses and recently also in narrow molecular-weight-distribution polymers, monodisperse polymer components, and supramolecular polymers. Together with their supramolecular orientational memory Frank-Kasper phases will provide a first access to biological precision. (2) The generality of the cogwheel double-helix, hat-shape deracemizing and “rigid” solid-angle tobacco mosaic virus-like supramolecular helical polymerizations accompanied by deracemization will be investigated and elucidated. They will provide homochiral assemblies, of biological precision and even higher, containing sequence-defined and monodisperse components obtained by deracemization. (3) The scope and limitations of self-interrupted living polymerization for the synthesis of monodisperse biological-like polymers by non-iterative methods will be investigated and elucidated. Alternative methodologies for the synthesis of monodisperse polymers will also be explored..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.