具有刺激响应性人工氯离子通道的构筑和跨膜输运性能研究

Rapid and important progress has been made in the simulation of selective transmembrane transport of anions using synthetic systems, and become a highly efficient method to study the function of natural anion transporters. However, the transport activity of most currently reported artificial systems are not regulatable, so it is an ongoing challenge to construct an artificial anion channel with stimuli-responsive activity and develop methods to gate the activity of the anion channels. In the previous studies, it was found that the side-chains attached to the pillararene could be induced to assemble into unimolecular tube through intramolecular hydrogen bonds. On this basis, the project proposed to attach multiple hydrogen bonding recognition sites and stimuli-responsive sites to the side-chains adopting the non-covalent interaction between the channel molecules and different anions, in order to design a kind of unimolecular artificial chloride channels with stimuli-responsive activities, and further establish the relevant characterization methods. It is proposed to screen the transport activities and selectivities of anion channels on vesicles and planar lipid bilayer, while the stimuli-responsive activities would be explored by adjusting pH or ligand binding. The successful execution of this project would not only highly simulate the function of natural transmembrane proteins, but also have be of great values for potential applications to construct biosensors and organic functional materials.

利用人工合成的体系模拟阴离子的选择性跨膜输运近年来取得了重要进展，已成为研究天然阴离子转运蛋白功能的重要手段之一。然而目前报道的人工体系多不具有可调控的输运功能，因此，构筑具有刺激响应性的人工阴离子通道并发展通道性能的调控方法是一个持续的挑战。本课题拟利用通道分子与不同阴离子之间的非共价相互作用为切入点，在利用分子内氢键诱导整个分子组装成单分子管的基础上，提出向柱芳烃骨架的侧链上引入多重氢键识别位点和刺激响应位点，发展一类具有刺激响应性的人工跨膜氯离子通道并建立相关表征方法。设计将在磷脂分子组装成的囊泡及平面脂双层上开展阴离子的跨膜输运能力和选择性研究，并采用调节pH和配体分子的方式探索阴离子跨膜输运的刺激响应性。本课题的成功实施，不仅可实现天然通道蛋白功能的高度模拟，在构筑生物传感器及有机功能材料方面也具有潜在的应用价值。

生命体中的细胞膜具有一定的选择透过性，只允许小的非极性分子通过自由扩散的方式进出细胞，对极性溶质和生物大分子高度不渗透，必须借助膜蛋白实现物质和能量的交换。大多数天然膜蛋白结构复杂，受到其功能启发，近年来化学工作者发展了很多人工体系来模拟天然通道蛋白的性能，其中单分子人工通道体系的构筑是该研究领域的难点。本项目基于通道分子与不同阴离子之间的非共价相互作用，利用分子内氢键诱导整个分子组装成单分子管状结构，构筑了基于柱芳烃的人工跨膜单分子通道。在磷脂分子组装成的囊泡上开展了通道分子对不同卤素阴离子及碱金属阳离子的跨膜输运选择性研究，探讨了侧链结构和通道分子跨膜输运效率之间的关系，为进一步结构优化及该类通道分子的结构及功能设计提供了一定的理论依据。