空腔内具有氢键供体位点的水溶性大环的合成、识别及应用研究

Molecular recognition is one of the central research topics for both supramolecular chemistry and biophysics, and is also the basis of artificial supramolecular systems and numerous biological functional systems. During the last half a century, artificial molecular recognition has made remarkable achievements. Nevertheless, it is still difficult for artificial molecular receptors to selectively recognize polar molecules in water, which is, however, commonplace for biomolecular receptors. This is because molecular recognition with hydrogen bonding in water is challenging. Inspired by the structures of biomolecular receptors, we proposed the concept of “endo-functionalized molecular tubes”, in which hydrogen bonding sites are incorporated inside the deep hydrophobic cavity of molecular tubes. Thus, with the cooperative action between hydrogen bond and hydrophobic effect, selective recognition of several polar solvent molecules in water has been achieved. In this project, we would like to perform a systematic and thorough research on the synthesis, modification and molecular recognition of several amide-based endo-functionalized molecular tubes; By using ITC, NMR, X-ray crystallography, fluorescence spectroscopy, and stopped-flow spectroscopy, we would like to reveal the relationship between molecular recognition and cavity structure, and understand the physical organic origins of hydrophobic effects and hydrogen bonding in water; In addition, we will also explore the applications of these macrocyclic receptors in the detection of environmental pollutants, chiral analysis, and self-assembly materials.

分子识别是超分子化学和生物物理学的主要研究主题，也是构成人工超分子体系和众多生物功能体系的基础。经过半个世纪的发展，人工分子受体已经取得了令人瞩目的成就，但是仍然很难在水中实现对极性分子的选择性识别。而这对生物分子识别却很常见。这主要是因为在水中利用氢键进行分子识别非常困难。受生物受体结构的启发，我们首次提出了“内修饰分子管”的概念，将氢键键合位点植入到疏水的深穴空腔中，利用疏水效应与氢键之间的协同作用，实现了对部分极性溶剂分子的选择性识别。在此基础上，本项目拟系统地探索多种酰胺内修饰分子管的骨架合成与侧链修饰方法，利用ITC、NMR、X-Ray单晶衍射、荧光光谱、停流光谱等手段揭示其结构变化与识别性能之间的构效关系，理解疏水效应以及氢键的物理有机化学本质，并探索这类新型大环主体分子在环境污染物检测、手性分析、以及超分子自组装材料等方面的应用。

分子识别是超分子化学与生物物理化学的主要研究主题，也是构建人工超分子体系和生物功能体系的基础。大环主体是人工分子识别的主要研究工具。经过半个世纪的发展，人工分子识别取得了令人瞩目的成就。然而，水相中功能分子的高效与选择性识别仍然是合成主体所面临的一个巨大挑战。针对这一难题，本项目通过模拟生物受体的识别口袋，提出了“内修饰空腔”的仿生研究理念，将氢键供体位点内植于深穴疏水空腔之中，设计合成了一类具有内修饰空腔的新型大环主体——酰胺萘管，系统研究了该类大环主体对极性分子、手性分子、药物分子、环境污染物等有机分子的水相选择性识别行为，揭示了内修饰空腔在水相选择性分子识别的物理有机化学本质，为水相选择性分子识别这一难题提供了解决方案。在分子识别研究的基础上，我们还探索了这类具有内修饰空腔的大环主体在手性分子的光谱分析、超分子耗散自组装、环境污染物的检测与去除、有机毒物的解毒、非共价生物偶联等领域的功能应用，为分析化学、环境科学、化学生物学等领域提供了新型研究工具。