酰腙类动态共价双亲分子的组装及其和生物膜的相互作用

The goal of this project is to combine the efforts of soft matter assembly, dynamic covalent reactions, as well as molecular recognition, in order to discover new strategies for achieving the efficient controlled assembly, dynamic modulation and chemical stimuli-responsiveness, as well as new function of amphiphilic aggregates, and to explore their interactions with biological membranes to lay the foundation for biological recognition. Dynamic covalent amphiphiles will be constructed in situ by combining hydrophilic and hydrophobic components using reversible acylhydrazone formation to minimize synthetic efforts and enhance structural diversity. The ordered aggregates from those dynamic amphiphiles will then be assembled and characterized, the driving force and mechanism of the self-assembly process will be elucidated, and their structure and function will be modulated by dynamic component exchange and supramolecular interactions, such as metal coordination and hydrogen bonding, in order to enhance the stimuli-responsiveness of the system. Based on these results, the interaction of amphiphilic assemblies and biological membranes will be investigated. The library of dynamic covalent amphiphiles will then be constructed for high-throughput screening to achieve the recognition and sensing of membrane components, such as head group phosphates. The results of this project will pave the way for future research in biomimic materials assembly and biological sensing.

本项目致力于将软物质组装、动态共价反应和分子识别有机结合起来，针对双亲分子聚集体的高效可控组装、动态调控和化学刺激响应性、新功能发现等关键问题，寻找双亲分子聚集体组装和调控的新模式，并探索它们和生物膜的相互作用，为生物识别奠定基础。设计并合成亲水基团和疏水基团组装模块，通过高亲和可逆酰腙生成反应原位组装动态共价双亲分子，减少合成步骤，显著提高动态双亲分子的多样性。进一步系统研究这些动态双亲分子的有序聚集体的组装和表征，探明组装驱动力和过程机理，并以酰腙官能团的识别位点为平台，使用动态组分交换和金属配位、氢键等超分子作用实现结构和功能动态调控，发现2-3个新型刺激响应体系。在上述基础上，阐明这些动态共价双亲分子聚集体和生物膜的相互作用机理，率先建立含多识别位点的动态双亲分子库，并通过高通量筛选实现细胞膜组分磷酸根的识别和传感。预期本项目的研究成果将为未来仿生材料组装和生物传感研究铺平道路。

腙类是一类常见的动态共价键，又含有氢键给受体等超分子识别位点，可用于响应性材料的构筑。本项目以酰腙键为平台，开展了酰腙类动态双亲组装体的设计合成、聚集体组装和调控以及传感功能研究。首先合成了结构多样并含有配位基团、亲疏水基团等不同识别位点的醛和酰肼基元，并通过它们的组合实现了酰腙双亲聚合物的一步合成组装。系统探究了含配位点酰腙的聚集体及其调控，发现具有对金属离子、阴离子溶剂、pH等的多重刺激响应性，并探究了组装形貌和机制；进一步通过亲疏水作用调控实现了具有相反温度响应的酰腙聚集体组装和解组装及其调控，模拟了生物膜及其和小分子的相互作用。以上述研究为基础，开展了酰腙组装体的化学传感功能研究，实现了铜离子、氰根离子、焦磷酸根等的检测。本项目研究结果为后续智能仿生响应材料的开发以及生物识别和传感奠定了基础。