生物技术启发的拓扑合成高分子制备及构效关系研究

拓扑结构是调控高分子性质的独特维度，但复杂拓扑高分子的合成仍存在极大挑战，主要在于难以实现高分子构象的精准控制与位点特异性的高效偶联。本项目受天然拓扑蛋白质的形成机制启发，拟将生物技术（包括方便分离或方便切割的多肽标签、可发生定点偶联的多肽标签以及可实现缠绕偶联的主动模板等）应用于水溶性合成高分子（如聚乙二醇）中，通过多肽片段的折叠及其与酶的特异性识别，辅以高效的点击化学工具以及金属离子配位的超分子模板，实现拓扑合成的高选择性和高效率，简化其纯化步骤，从而制备一系列传统方法难以获得的模型（多）索烃拓扑高分子，并通过变化其分子量、化学组成、连环数目等，初步探究（多）索烃高分子的结晶性、相分离、动力学等物理特性，提炼拓扑结构性能关系及其內秉规律，以期发现新奇的分子性质和物理图景，具有重要的理论和实践意义。

Topology is a unique dimension in macromolecular engineering. While there has been tremendous progress in the synthesis of polymers with relatively simple topologies (e.g., linear, branched and cyclic), it remains a daunting challenge to synthesize polymers with complex topologies, such as links or knots. The problem mainly lies in the difficulty in the precise manipulation of polymer chain conformation and site-specific ligation. Inspired by the formation mechanism of both natural and artificial topological proteins, we wish to apply the chemical tools in biotechnology to synthetic macromolecules to address these challenges. Such tools include the peptide tags for selective purification, for selective cleavage by proteases, for site-specific ligation, and for “active-template” synthesis of heterocatenanes. In this proposal, we plan to attach these peptide tags onto water-soluble polymers such as poly(ethylene glycol) and prepare a series of polymers with complex topology that are otherwise difficult to prepare by conventional methods, such as [n]catenane. The synthesis is empowered by the synergy between peptide/metal-ligand assembly and efficient reactions. The complication in purification is circumvented by selective purification with peptide tags and the characterization of topology is facilitated by enzyme-mediated transformations. This project will give a library of model topological polymers with various molecular weight, chemical composition, and topology for a systematic study on their physical properties, such as crystallinity, phase separation, kinetics, and for revealing the topological effects on structure-property relationship. Through these efforts, we aim to discover novel molecular properties and physical pictures from such unconventional macromolecules.