基于氮杂环鎓盐的新型动态共价键和复杂动态信号级联体系

Signal transduction plays a vital role in many biological processes. The research of dynamic covalent chemistry is one of the cutting-edge areas of organic and supramolecular chemistry and has found key applications in the construction, modification, as well as modulation of molecular assemblies. In order to closely mimic complex biological systems, such as cellular communications, the goal of this project is to discover nitrogen-heterocyclic onium salts based novel dynamic covalent bonds and to achieve the controlled assembly as well as intelligent modulation of complex dynamic covalent signaling cascades through bridging the fields of signal transduction and dynamic covalent chemistry. First, a series of reversible covalent interactions, including addition reactions and condensation reactions, will be developed based on the concept of “reactivity based dynamic covalent chemistry” proposed recently by the principal investigator in conjunction with the diverse structures as well as reactions of nitrogen-heterocyclic onium salts. Next, dynamic signaling cascades will be constructed through the coupling of one reversible covalent reaction with a second reversible reaction, an acid-sensitive process, or a photo-controlled molecular switch, and the mechanism for assembly and modulation will also be investigated in detail. Building on those foundations, dynamic multistep cascades and multiresponsive dynamic cascades will be explored in order to further enhance the systematic complexity. The dynamic covalent reactions and cascades developed herein could find applications in the research of dynamic assembly, chemical sensing, and biological regulation.

信号转导在生命体系中发挥关键作用，而动态共价化学是当今有机超分子化学的前沿领域之一，在组装体构筑、修饰、调控等多个方面有重要应用。为模拟细胞通讯等复杂生命过程，本项目拟将信号转导和动态共价化学有机融合起来，致力于开发基于氮杂环鎓盐的新型动态共价键和复杂动态信号级联体系，解决动态共价级联体系的高效可控构筑和智能调控等关键科学问题。首先，围绕申请人提出的“基于反应性的动态共价化学”概念开展研究，结合氮杂环鎓盐的结构和反应多样性，开发基于动态加成和缩合反应的可逆共价键。其次，将动态反应和另一种动态反应、酸敏感过程或光控分子开关偶联起来，组装并调控动态共价级联体系，并探究动态组合库中的自分类现象。在上述基础上，探索动态多步级联体系和多重刺激响应级联体系，进一步提高系统复杂性，更加紧密地模拟复杂生命体系。预期本项目研发的动态共价键和动态级联体系将在动态组装、化学传感、生物调控等领域具有重要应用。

动态共价键兼具共价键的稳定性和超分子作用的动态可逆性，在构筑功能分子、组装和材料方面具有广泛应用，因而发展新型动态共价键和调控机制具有重要科学意义。本项目以结构多样的氮杂环鎓盐反应性为平台，开发了系列新型动态共价体系，进而用于级联体系和反应网络等复杂化学系统构建，并开展了分子识别和化学传感功能化探索。首先设计合成了10-甲基吖啶盐、5-甲基菲啶盐等氮杂环鎓盐，探究了它们和胺、硫醇等亲核试剂的动态加成反应，总结构效关系，利用π堆积等弱作用实现对动态组装的调控。为进一步平衡氮杂环鎓盐的反应性和稳定性，利用环链互变异构体开链醛和环状半缩胺原位产生的氮杂环鎓盐及双重反应性控制，实现C-N、C-O、C-S动态键的高效构筑和选择性切换，通过给受体轨道作用进行调控，进而在结构各异的骨架（例如2,2’位取代联芳基结构和邻位取代苯甲醛结构）证实了该策略的通用性。在上述基础上，经动态平衡的相互作用构筑质子传递信号级联体系和可切换多态反应网络等复杂化学系统，实现分子开关和发光材料的多重刺激响应性控制，并用于离子识别和蒸汽传感。本项目的研究成果丰富了动态共价键化学的构筑基元和调控机制，为后续分子识别、动态组装、智能材料研究奠定基础。