序列精确高分子合成新方法

序列精确高分子（Sequence-Defined Polymer）是一类单分散且具有确定单体单元序列分布的高分子。生物大分子如核酸和蛋白质均是序列精确高分子，其精确的序列结构确保了其在生命体系中复杂功能的精确表达。基于此，序列精确高分子合成已成为高分子化学领域重要研究内容。本项目将研究各类点击反应的正交性，建立串联多（≥3）正交点击反应库。并将以其为聚合反应发展合成序列精确高分子迭代次序和指数增长新方法，改善现存方法的缺陷并丰富所得序列精确高分子的序列种类和排布。将重点发展三种合成新方法：发展基于串联四正交点击反应的迭代次序增长新方法，实现双向不对称同时增长序列精确高分子链，解决现存双向迭代次序增长法仅能合成对称序列结构高分子的缺陷；发展基于串联三正交点击反应的迭代指数增长新方法，消除现存迭代指数增长法对保护基化学的依赖；结合点击反应组合和分子内环化策略，发展一种全新的迭代指数增长合成法。

Sequence-defined polymer has unique characteristics of monodispersity and perfectly defined monomer sequences. Biomacromolecules like nucleic acids and proteins all belong to sequence-defined polymers. It is the perfectly defined monomer sequences that guarantees their advanced functionalities in living system. Inspired by this, the research on sequence-defined polymer synthesis has become a hot topic in the field of polymer chemistry. In this proposal, we are going to intensely investigate the orthogonality of all kinds of click reactions and discover a library of multi-orthogonal (≥3) click reaction combinations. Using them as polymerization reactions, we are going to develop novel iterative sequential and exponential growth polymerization methods for preparing sequence-defined polymers. By virtue of these novel synthetic methods, we are going to improve the drawbacks of traditional iterative polymerization methods and expand the diversity of the resultant sequence-defined polymers. This proposal will develop at least three types of iterative polymerization methods. The first one is a novel bidirectional iterative sequential growth polymerization method developed on a combination of four orthogonal click reactions, which will grow sequence-defined polymer chains by simultaneously bonding different monomers at both polymer chain ends. This novel method will eliminate the drawback of the traditional bidirectional iterative sequential growth polymerization methods for producing sequence-defined polymer chains with only a symmetrical type of monomer sequences. The second one is a novel iterative exponential growth polymerization method developed on a combination of three orthogonal click reactions. This novel method will eliminate the usage of group protecting/deprotecting reactions required by the traditional iterative exponential growth polymerization methods. The third one is a novel iterative exponential growth polymerization method developed on the combination of multi-orthogonal click reactions and ring-closure of polymer chain technique.