Synthetic Approaches to Semi-Sequenced Copolymers

大自然通过将一组称为单体的基本分子组合成特定的序列，将特性编码成大分子，如DNA和蛋白质。例如，蜘蛛丝蛋白从一组特定的氨基酸单体序列中获得了其异常坚韧的特性。然而，这种控制聚合物等大分子特性的模型很难在非生物材料中模拟，因为在制备这种类型的完美测序分子方面存在挑战。在美国国家科学基金会大分子、超分子和纳米化学项目的支持下，匹兹堡大学的Tara Meyer教授进行了研究，以提高我们对如何精确控制序列以获得所需聚合物性能的理解。这项工作预计将在科学、技术和教育方面产生重大影响。新的合成方法和单体序列及其合成性质的研究具有相当大的科学影响。序列并不需要完美才有用，这一证明可以转化为在工业生产的聚合物中增加使用序列，这是一种潜在的技术优势。最后，研究生和本科生参与研究，特别强调确保来自各种背景的受训者的广泛参与，应有助于建立一支准备充分的科学工作队伍。Meyer小组已经成功地制备了完全有序的、可生物降解的、无毒的聚合物，称为聚（乳酸-羟基乙酸）s (PLGAs)，并证明了它们的性质与序列的依赖性。不幸的是，这些完美测序的PLGAs和几乎所有其他测序聚合物的制备过于复杂和昂贵，无法扩展到大多数应用中。研究小组认为，解决这一障碍的一种方法是回答以下两个问题：“拥有完美的序列是否至关重要？”和“具有75%正确序列模式的聚合物是否可能几乎与具有100%正确序列的聚合物一样高性能？”该项目的目标是通过开发一种新的、更具可扩展性的方法来解决这些问题，该方法可以制备具有“刚好足够”序列的聚合物，然后测试这些半序列共聚物与完美类似物的性能。介绍并开发了一种新的平行/连续合成策略，其目标是创建具有中间水平控制单体顺序的半序列阶跃生长共聚物。受经典聚氨酯合成的启发，平行/连续策略包括平行地创造具有相似骨架但不同序列的成分控制的预低聚物。这些预低聚物的连续反应产生半序列共聚物，就单体类型而言，其组成均匀，但具有节段结构。仔细的实验设计和使用流动系统的方法的实现可以实现具有不同程度的精细（单个单体）和过程（段级）顺序控制的材料。将半序列共聚物与完全序列材料的性质进行比较，提高了对序列效应表现的各种机制的理解。最终，这项研究可能会转化为先进塑料和材料制造的新技术。

Nature encodes properties into large molecules, like DNA and proteins, by combining a set of building block molecules, called monomers, into specific sequences. Spider silk protein, for example, derives its exceptionally tough nature from a specific sequence of amino acid monomers. This model for controlling properties in large molecules like polymers has been difficult to emulate in non-biological materials, however, because of the challenge in preparing perfectly sequenced molecules of this type. With the support from the NSF Macromolecular, Supramolecular and Nanochemistry Program, Professor Tara Meyer at the University of Pittsburgh conducts research to enhance our understanding of how precisely the sequence needs to be controlled to attain the desired polymer properties. This work is expected to have a significant impact scientifically, technologically, and educationally. The new synthesis method and the study of monomer sequence and their resultant properties represent a considerable scientific impact. The demonstration that sequence need not be perfect to be useful could translate into the increased use of sequence in industrially-produced polymers, a potential technological benefit. Finally, the involvement of graduate and undergraduate students in the research, with a particular emphasis on ensuring broad participation of trainees from all backgrounds, should contribute to a well-prepared scientific workforce.The Meyer group has successfully prepared perfectly sequenced, biodegradable, non-toxic polymers called poly(lactic-co-glycolic acids)s (PLGAs) and demonstrated the dependence of their properties on sequence. Unfortunately, the preparation of these perfectly sequenced PLGAs, and almost all other sequenced polymers, is too complicated and expensive to scale up for most applications. The research team thinks that one way to address this barrier is to answer the following two questions: "Is it essential to have a perfect sequence?" and "Is it possible that a polymer with a sequence pattern that is 75% correct would be almost as high performing as a polymer whose sequence is 100% correct?" The goal of this project is to address these questions by developing a new, more scalable method for preparing polymers with "just enough" sequence and then testing the properties of these semi-sequenced copolymers against perfect analogues. A new parallel/successive synthetic strategy is introduced and developed with the goal of creating semi-sequenced step-growth copolymers with an intermediate level of control over monomer order. Inspired by the classic synthesis of polyurethanes, the parallel/successive strategy involves the creation, in parallel, of compositionally controlled pre-oligomers with similar backbones but differing sequences. The successive reaction of these pre-oligomers produces semi-sequenced copolymers with a homogeneous composition in terms of the types of monomers present, but a segmented structure. Careful experimental design and the implementation of the method using a flow system can be implemented to yield materials with varying degrees of fine (monomer-by-monomer) and course (segment-level) sequence control. The comparison of the properties of the semi-sequenced copolymers with those of the perfectly sequence materials improves the understanding of the various mechanisms through which sequence effects manifest. Ultimately, this research may be translated into new technologies in advanced plastics and materials manufacturing.