纳米或亚纳米管在分子水平的物质输运、分离和检测方面具有广泛的应用前景，是当前纳米科学和超分子化学领域研究的前沿热点。课题组前期工作发现具有刚性骨架的六元（间苯乙炔）大环化合物能够通过π-π堆积和侧链的分子间氢键作用形成螺旋管状自组装体，具有良好的氢离子、钾离子通道性能以及水通道性能。构筑长度可控且结构稳定的此类有机纳米管将极大地促进纳米空间限域下的物质传输过程及机理的系统研究。本博士学位论文设计并成功合成得到了通过肽链串连六元（间苯乙炔）大环的分子纳米管寡聚体，并通过多种手段研究了其组装体的稳定性，平面脂双层研究发现寡聚体形成的纳米管具有突出的离子通道传输性质。具体研究内容及成果如下：

论文第一部分内容对近几年常见的纳米管构筑手段进行了简明扼要的综述，其中包括碳纳米管、自组装有机纳米管和单分子纳米管，同时也较为系统地总结了我们课题组近几年对大环自组装的研究成果。

论文第二部分在对构筑长度可控且结构稳定纳米管工作梳理的基础上，提出将大环作为氨基酸取代基，通过取代氨基酸的逐步缩合得到肽链串连大环寡聚体的设计思路和合成路线（单肽链系列大环及其寡聚体编号：MC-1-Ox，x代表大环的个数）。接着通过多步有机反应分别合成了大环的双烷基侧链单元、β-丙氨酸及双烷基酰胺侧链修饰苯乙炔半环二炔单元和双烷基酰胺侧链修饰的苯乙炔半环二碘单元，最后通过偶联反应的半环对接法得到了含有β-丙氨酸侧链和双烷基酰胺侧链的大环单体MC-1-O1。接着一部分MC-1-O1脱去Boc保护基，另一部分水解掉甲酯，两部分产物通过缩合反应得到大环二聚体MC-1-O2。通过类似的方法，最终得到了肽链串连的六元（间苯乙炔）大环四聚体MC-1-O4。四聚体MC-1-O4的合成总共25步反应，总收率为1‰。合成的关键中间体和目标产物进行了氢谱、碳谱和高分辨或者MALDI-TOF质谱的表征确认。

论文第三部分，对合成肽链串联寡聚体目标化合物中的关键步骤进行了系统优化。首先利用廉价易得的溴代物代替碘代物作为初始原料，较为便捷高效地得到了部分中间体。另一方面，采用氨基定位、氯化碘的碘代反应将对氨基苯甲酸转化为3,5-二碘-4-氨基苯甲酸，然后通过重氮化反应将氨基转化为氢原子，高效地合成了3,5-二碘苯甲酸。此外，对于路线中关键中间体半环化合物的合成，先合成具有不同反应活性位点的3-溴-5-碘苯甲酰胺代替完全依靠统计学概率实现单边取代的3,5-二碘苯甲酰胺，平均收率由45%提高到70%。经过路线优化，虽然整条路线增加了两步反应（由25步增加到27步），但是平均总收率增加了3倍，达到3‰。同时优化后的路线中减少了用柱层析分离纯化的次数和操作难度，提高了合成效率。另外，为了得到更加稳定的以六元（间苯乙炔）大环为基本单元构建的纳米管，基于路线优化结果，对双肽链串连的大环寡聚体进行了有益的探索（双肽链系列大环及其寡聚体编号：MC-2-Ox，x代表大环的个数），通过26步反应得到了双肽链单环产物MC-2-O1，进一步通过串连反应成功得到了双肽链串连六元（间苯乙炔）大环二聚体MC-2-O2。由于串联过程中有多个反应位点导致更多的副产物，双肽链大环二聚体的总收率不足1‰。

论文第四部分工作中，分别采用核磁共振氢谱、紫外-可见光光谱、圆二色谱以及荧光光谱研究了六元（间苯乙炔）大环单体MC-1-O1、二聚体MC-1-O2和四聚体MC-1-O4的组装性能，考察了不同溶剂、混合溶剂以及不同温度对组装行为的影响。结果表明，弱极性溶剂如四氯化碳中有利于寡聚体的组装，极性溶剂和温度升高会减弱组装。四聚体MC-1-O4相比于二聚体MC-1-O2和单体MC-1-O1，表现出更强的组装稳定性。在平面脂双层离子通道实验中发现，六元（间苯乙炔）大环四聚体MC-1-O4能够形成稳定的通道，对氢离子和钾离子单通道持续通导时间能够长达数分钟，远远超出文献中类似化合物的通道稳定性。

综上所述，本论文工作通过引入肽链作为连接单元成功将大环串连起来，得到了单链大环单体、二聚体和四聚体以及双链大环单体和二聚体，并通过一系列波谱实验证实了随着聚合度的增加，大环寡聚体形成的纳米管更加稳定，离子通道稳定性更加突出。本论文的研究工作为设计合成长度可控稳定性高的分子纳米管提供了一种有效策略，对于发展高性能的分子尺度分离介质及其在功能材料和生命科学方面应用有着重要意义。

Nanotubes or sub-nanotubes have broad application prospects in molecular-level material transport, separation, and detection, and are currently at the forefront of research in the fields of nanoscience and supramolecular chemistry. Previous work of our group has found that shape-persistent hexakis(m-phenyleneethynylene) (m-PE) macrocycles were able to form helical tubular self-assemblies through π-π stacking and intermolecular hydrogen bonding of side chains. These self-assemblies exhibit excellent channel functionality for transporting proton and potassium ions, and water molecules. Constructing such organic nanotubes with controllable length and good stability will greatly promote the systematic study of material transport processes and mechanisms under nanoscale confinement. In this dissertation, peptide-linked oligomers of molecular nanotubes composed of m-PE macrocycles were designed and successfully synthesized. The stabilities of their assemblies were studied by using various spectral and spectroscopies. It was found that the molecular nanotubes formed by oligomers showed the outstanding ion channel transport properties through planar lipid bilayer studies. The specific research contents and achievements are shown as follows:

In the first part of this dissertation，a brief summary of common nanotube construction methods in recent years was provided, including carbon nanotubes, self-assembled organic nanotubes, and single-molecular nanotubes. It also systematically summarized the research results of our research group on macrocycle self-assembly in recent years.

In the second part of this dissertation, we analyzed the work of our research group in constructing nanotubes with controllable length and stable structure, and proposed a synthetical strategy for oligomers of macrocycles linked by peptide chains, in which m-PE macrocycles was designed as the substitute groug of b-anline and oligomers were constructed through amino acid condensations (The single-peptide chain series of macrocycles and their oligomers are labeled MC-1-Ox, where ”x” represents the number of macrocycles.). Subsequently, we synthesized the building blocks of the double alkyl side chain unit, β-alanine and alkylamide side chain-modified phenylethynylene half-cyclic diynes unit, and alkylamide side chain-modified phenylethynylene diiodide unit through multi-step organic reactions. Then, the macrocycle monomer MC-1-O1 containing β-alanine side chains and alkylamide was obtained through coupling reaction using half-cyclic docking method. After the deprotection of the Boc group and the hydrolysis of the methyl ester group of MC-1-O1, respectively, the resulted two products were condensed through a coupling reaction to afford the macrocyclic dimer MC-1-O2. Following the similar methods, the peptide-linked (m-PE) macrocycle tetramer MC-1-O4 was finally obtained. The synthesis of tetramer MC-1-O4 involved 25 steps of reaction with a total yield of 1‰. Key intermediates and the target compounds were fully characteriezed with ¹H NMR, ¹³C NMR and mass spectroscopies.

In the third part of this dissertation, the key steps in synthesizing the target compounds of oligomers linked by peptide chains were systematically optimized. Firstly, inexpensive and readily available bromides were used instead of iodides as starting materials to more conveniently and efficiently prepare some intermediates. Specifically, 3,5-diiodo-4-aminobenzoic acid was efficiently synthesized by converting p-aminobenzoic acid to 3,5-diiodo-4-aminobenzoic acid through amino group localization and iodination with iodine chloride, followed by diazotization to convert the amino group to a hydrogen atom. In addition, for the synthesis of key intermediate half-cyclic compounds, 3-bromo-5-iodobenzamide with different reactive sites was synthesized to achieve one-sided substitution of 3,5-diiodobenzamide, increasing the average yield from 45% to 70%. Although the entire route was increased by two steps (from 25 steps to 27 steps) after optimization, the average total yield was increased by three times, up to 3‰. At the same time, the number of purifications by column chromatography was reduced in the optimized route, which improved the synthesis efficiency. On the other hand, based on the optimization results of the route, more stable nanotubes based on (m-PE) macrocycles as basic units linked by double peptide chains were further explored (The double-peptide chain series of macrocycles and their oligomers are labeled MC-1-Ox, where “x” represents the number of macrocycles). The double-peptide chain monomer MC-2-O1 was obtained through a 26-step reactions and further successfully linked into a double-peptide chain-linked (m-PE) macrocycle dimer MC-2-O2. However, due to the presence of multiple reaction sites during the condensation process, a total yield of less than 1‰ for the double-peptide chain macrocycle dimer was affored due to more by products resulted.

In the fourth part of this dissertation, the assembly properties of (m-PE) macrocycle monomer MC-1-O1, dimer MC-1-O2, and tetramer MC-1-O4 were studied using HNMR spectroscopy, UV-vis spectroscopy, circular dichroism spectroscopy, and fluorescence spectroscopy. The effects of different solvents, mixed solvents, and temperatures on the assembly behavior were investigated. The results showed that weakly polar solvents such as carbon tetrachloride were conducive to oligomer assembly, while polar solvents and increasing or decreasing temperature weakened the assembly. Tetramer MC-1-O4 exhibited stronger assembly stability compared to dimer MC-1-O2 and monomer MC-1-O1. In planar lipid bilayer ion channel experiments, it was found that (m-PE) macrocycle tetramer MC-1-O4 was able to form stable channels with a single-channel conductance time for proton and potassium ions lasting for several minutes, far exceeding the channel stability of similar compounds in the literatures.

In summary, by using peptide chains as connecting units, single-chain macrocycle monomers, dimers, and tetramers as well as double-chain macrocycle monomers and dimers were successfully designed and synthesized in this thesis. Through a series of spectroscopic verifications, it was confirmed that with the increase of polymerization degree, the nanotubes formed by macrocycle oligomers were more stable and the stability of ion channels was more prominent. The research work in this thesis provides an effective strategy for designing and synthesizing molecular nanotubes with controllable length and high stability, which is of great significance for developing high-performance molecular-scale separation media and their applications in functional materials and life sciences.