基于柱芳烃人工跨膜通道的构建与输送研究

【作者】 陈磊；

【导师】 侯军利；

【作者基本信息】 复旦大学 ， 有机化学， 2013， 硕士

【摘要】 柱芳烃是由对苯二酚通过桥联亚甲基连接而成的柱状结构,由于其独特的对称结构以及卓越的分子识别能力,近期受到越来越多科研工作者的关注,并成为一类新的大环主体分子。我们以柱芳烃为基本骨架发展单分子人工跨膜通道,从而模拟通道蛋白的功能,并为研究物质跨膜输送的机理提供简单的模型。第一部分工作,我们以柱[n]芳烃(n=5,6)为骨架,利用苯丙氨酸三肽的衍生化,发展了一类人工跨膜氨基酸通道。通过1H NMR与IR实验,我们证实这类通道分子具有管状结构。通过动力学荧光实验,我们证实这类通道分子具有良好的嵌膜能力,并且对氨基酸显示出高效的跨膜输送能力。此外,由于这类通道分子具有手性,进一步研究发现该通道分子对手性氨基酸的输送也具有手性选择性,实现了对天然氨基酸通道功能的模拟。该类通道分子将在氨基酸的分离纯化方面具有良好的应用前景。第二部分工作,通过柱[5]芳烃的胺解反应,我们得到了一种烷基链内翻结构的柱芳烃。通过X-Ray单晶衍射证实分子内氢键的诱导作用导致烷基链向孔穴内弯曲。同时,我们对柱芳烃与一系列不同长度烷基二胺、单胺的反应进行了动力学研究。实验发现,分子内氢键即能稳定这种内翻结构,又能稳定反应中间体。因此,柱芳烃与二胺的反应展现了不同的速率常数。这类内翻结构的柱芳烃为发展具有可调控功能的人工跨膜输送体系提供了良好的模块。更多还原

【Abstract】 The new generation of macrocycles has received great attention for their unique tubular structure and excellent molecular recognition properties. Pillararene is a symmetrical pillar architecture in that hydroquinones are connected by methylene bridges. We are interested in building of single-molecular transmembrane channels from pillararenes to mimick the function of channel proteins.In the first part, peptide-appended pillar[n]arene (n=5,6) derivatives have been synthesized.1H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC50=0.002mol%). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels. And the applications of artificial channels have a good prospect in the separation and purification of amino acids.In the second part, pillar[5]arenes with introverted amino groups were produced through aminolysis. X-ray analysis demonstrated that the intramolecular hydrogen bonding induced the amino group toward the inner space of the cavity. The kinetic studies and molecular modelings revealed that the hydrogen bonding also contributed to the acceleration of the aminolysis through stabilizing the intermediate. Arranging a functional group inward of pillar[5]arene might generate a new kind of functional group introverted cavity. With this structure, we can design the regulated artificial channel, which is under investigation.更多还原