水相中三维主体分子的自组装及其超分子功能

The construction of host molecules that have cavities with limited volume, as well as realizing their supramolecular functions, always represent the focuses of supramolecular chemistry. The traditional synthetic strategies, relying on irreversible organic reactions, often have relative low yields. Dynamic approaches, relying on the formation of metal-ligand coordinative bonds, can efficiently increase the yields. However, the use of metal often leads to high expense (e.g., Pd, or Pt), or sometimes toxicity (e.g., Cu, Co, Ni, Ga, Ce, etc.). The dynamic covalent approaches relying on imine base, could avoid using metal. However, this method cannot be used in aqueous systems. .In this project, we propose to develop a novel dynamic covalent synthetic approach, based on the formation of hydrazone bond (-C=N-NH-), which could be used to accomplish the highly efficient self-assembly of three-dimensional organic host molecules with complex structures in water. We also proposed to investigate the relationship between the host-guest binding affinities and a variety of factors, including the sizes of host-guest molecules, hydrophobicity and π-electron density of the building blocks, solvents, temperatures, ionic strength and acidity. We proposed to explore the molecular behaviors of the guest molecules in the cavities of the hosts. These self-assembled hosts would be used for the detection, storage and separation of guest molecules. The cavities of these hosts would also function as artificial enzymes to catalyze the reactions of the guest molecules in an efficient, selective and mild manner. The switching behavior of hydrazone linkages is also going to be taken advantage of, to develop drug delivery systems for targeted therapy of cancer.

构筑具备限域空腔的主体分子并实现其超分子功能一直是超分子化学领域研究的焦点。依赖于不可逆化学反应的传统合成法一般产率低下。基于金属配位键的主体分子动态合成法解决了产率的问题，然而金属的使用往往带来了昂贵的价格（如Pd)，或毒性（如Cu，Co, Ni, Ga，Ce等）。基于席夫碱等弱共价键的合成方法避免了金属的使用，然而无法适用于水溶液体系。.面对这些问题，该项目拟发展一类基于腙键（-C=N-NH-）的动态共价合成法，完成三维复杂有机主体分子在水溶液中的高效自组装。考察主客体分子的尺寸、构筑功能单元的亲疏水性与π电子云密度、溶剂、温度、离子强度等因素对于主客体结合能力的影响，探索客体分子在主体分子的限域空腔中的分子行为。将自组装形成的超分子体系用于客体分子的检测、存储、分离；实现在限域空间内对客体小分子高效的专一的催化；并利用腙的酸碱响应性发展一类抗癌药物的靶向输送体系。

本项目针对基于亚胺缩合反应的动态共价键和水溶液不兼容的问题，提出利用杂原子共振稳定亚胺的策略，发展了基于酰腙或肟的新型动态共价合成方法，实现了纯有机分子在水相中高效自组装，避免了传统自组装方法中有机溶剂、贵金属或有毒金属的使用。在水溶液中实现了一系列分子的高效甚至定量自组装，包括笼状分子，大环分子，互锁分子等。通过利用水溶液中的疏水效应，驱动了一些自组装分子对客体分子的识别。在本项目的资助下，共发表SCI论文26篇，包括Angew. Chem. Int. Ed. 7篇, Org. Lett. 4篇，J. Org. Chem.1篇，Chem.Commun.6篇， Nat.Commun.1篇，J. Am.Soc.Chem.3篇，Chem.Sci.1篇，Sci.Adv.1篇，Supramol. Chem.1篇，ChemPlusChem 1篇，Chem.Eur.J. 1篇。