Supramolecular Self-Assemblies On The Basis Of Pillararenes-Based Host-Guest Recognitions And Their Applications

It is of continuing interests to design and synthesize novel macrocyclic hosts because of their important roles in the development of supramolecular chemistry. It has been demonstrated that the arrival of any new generation of macrocycles can not only accelerate the development of supramolecular chemistry but also provide new opportunities for material science. Crown ethers, cyclodextrins, calixarenes and cucurbiturils are the classical four generations of macrocyclic hosts in supramolecular chemistry, and they exhibit fantastic applications in different fields. In 2008, a novel host molecule, named as pillararene, was synthesized. Pillararenes, a new kind of cyclic oligomers, were made up of hydroquinone or hydroquinone ether derivatives that are connected by methylenes at para-positions, resulting in the formation of rigid pillar structures. Due to their unique structure and excellent host-guest properties, pillararenes have been the focus of supramolecular chemistry over the past few years. In this dissertation, we focus on the host-guest recognitions between pillararenes and different guests, including anions and cationic molecular guests. On the basis of the pillararene-based host-guest recognition motifs, we fabricated a series of supramolecular amphiphiles and studied their self-assembly in water. Moreover, we applied the aggregates formed from these supramolecular amphiphiles in bio-relevant applications, such as drug delivery, cell imaging and so on.In the first part, we designed and synthesized a non-symmetric pillar[5]arene through click chemistry. Due to the unique geometric structure of pillar[5]arene, multiple C-H···X hydrogen-bonding interactions between the host and the anions formed and greatly improved their binding affinity. We found that the pillar[5]arene-based host could selectively complex with fluoride, because the electronegativity and basicity of the fluoride anion were the strongest and its size was suitable for the cavity of pillar[5]arene. More interestingly, the pillar structure of the host changed into conical structure upon complexation with fluoride.In the second part, cavity extended pillar[5]arenes, containing electron-rich naphthyl groups on both sides or on one side of the pillar[5]arene backbone were designed and prepared. Novel cavity extended pillar[5]arenes containing electron-rich naphthyl groups have been demonstrated to have enhanced binding affinity to linear guests containing electron-deficient 4,4’-bipyridinium units. The importance of size effect, charge density, cooperative effect and C-H···π interactions have been investigated, which play significant roles in the complexation of these host-guest systems.In the third part, we established a photo-responsive host-guest recognition motif. The trans form of an azobenzene-containing guest can complex with a pillar[6]arene while it can not complex with pillar[5]arenes due to the different cavity sizes of the pillar[6]arene and the pillar[5]arenes. Upon irradiation with UV light, the conformation of the guest changed from the trans form to the cis form and the threading of the guest through the cavity of pillar[6]arene was prohibited due to the size mismatch, but it rethreaded through the cavity again upon visible light irradiation. This photo-controlled switch of threading results in microstructural changed of the self-assembled aggregates formed from the host-guest inclusion eomplex. These phenomena have been demonstrated by various characterization techniques. Therefore, this new efficient pillar[6]arene-based host-guest recognition motif exhibited a photo-responsive threading-dethreading switch in organic solvents. Acting as a good supplement to the existing widely used cyclodextrin/azobenzene recognition motif in water, it will have a broad application in the future fabrication of more sophisticated photoresponsive supramolecular systems.In the fourth part, we successfully synthesized the first water-soluble pillar[6]arene bearing carboxylate anionic groups on both rims. In contrast to the tubular aggregates of amphiphilic guest, the host-guest complex self-assembled into vesicles, induced by a curvature-dependent mechanism. This reversible transformation between nanotubes and vesicles could be easily controlled by changing the pH. Furthermore, the confined hydrophobic cavity of the water-soluble pillar[6]arene could be ultilized to interact with a neutral guest containing a pyerenyl group, which caused the formation of a 1:1 [2]pseudorotaxane. This host-guest complex was a good supramolecular dispersant for MWNTs in water. By adjusting the solution to acidity, the predispersed MWNTs reaggregated, and this process could be reversibly pH-controlled.In the fifth part, the complexation between a water-soluble pillar[6]arene (WP6) and paraquat (PQ) in water was investigated. They could form a stable 1:1 [2]pseudorotaxane with an extremely high association constant of (1.02±0.10)×108 M-1 mainly driven by electrostatic interactions, hydrophobic interactions and π-π stacking interactions. This novel recognition motif was further used to control the aggregation of a complex between WP6 and an amphiphilic paraquat derivative (C2V12) in water. The controlled release of water-soluble dye molecules from the vesicles the formed from the host-guest complex the could be achieved by the collapse of the vesicles into the micelles upon changing the solution pH to acidity. Additionally, the high binding affinity between WP6 and paraquat could be utilized to efficiently reduce the toxicity of paraquat. After the formation of a stable host-guest complex between WP6 and paraquat, less opportunity was available for paraquat to interact with the reducing agents in the cell, which made the generation of its radical cation more difficult, resulting in the efficient reduction of paraquat toxicity.In the fifth part, we designed a novel pillar[5]arene-based macrocyclic amphiphile with galactoses as the hydrophlic part and alkyl chains as the hydrophobic part. Due to the existence of intermolecular hydrogen bonds between the galactoses and the van der Waals interactions between the alkyl chains, the macrocyclic amphiphile self-assembled into vesicles in water and was gradually transformed into nanotubes after standing for one week. The biocompatible galactoses coating the sweet nanotubes endowed them with interesting biofunctions, which could act as excellent cell glue to effectively agglutinate E. coli.In the seventh part, four-armed TPE derivatives containing electron-rich naphthalene (TPE-NP) and electron-deficient paraquat (TPE-PQ) groups, respectively, were designed and synthesized. Driven by charge-transfer (CT) interactions, a complex formed between TPE-NP and TPE-PQ. It self-assembled into nanorods in a 1D packing mode, resulting in restriction of intramolecular rotation to enhance the AIE effect significantly. A difunctional negatively charged water-soluble pillar[6] arene (AH) was employed to reduce the toxicity and enhance the membrane permeability of TPE-PQ by forming a stable inclusion complex (AH4(?)TPE-PQ) with TPE-PQ. A ternary system containing AH, TPE-NP and TPE-PQ was utilized as a selective imaging agent for cancer cells due to the pH-responsiveness of AH. Compared to the physiological pH of 7.4, the pH in tumor tissue and endosomes is more acidic, resulting in the disassembly of the host-guest complex AH4(?)TPE-PQ and the formation of the AIE-enhanced CT complex between TPE-NP and TPE-NP in the cancer cells.In the eighth part, a novel ternary drug delivery system (DDS) was constructed using a photodegradable anticancer prodrug (Py-Cbl), a water-soluble pillararene supramolecular container (WP6), and a diblock copolymer methoxy-poly(ethylene glycol)114-block-poly(L-lysine hydrochloride)2oo (PEG-b-PLKC). The water solubility of Py-Cbl was enhanced effectively by forming a stable host-guest inclusion complex with the pillararene (WP6(?)Py-Cbl). Accompanied with the release of the anticancer drug, the fluorescence colour of the cell changed from bright blue to dark blue, which could be used to monitor the release of the anticancer drug. On the other hand, the biocompatibility and the membrane permeability of the DDS were improved effectively after the formation of ternary polyion complex (PIC) micelles with WP6(?)Py-Cbl and the PLKC block as the core and the PEG block as the shell. This was used to follow the drug release process. This DDS successfully addressed three important issues:1) enhancement of the water solubility of the anticancer prodrug; 2) controlled release of the anticancer drug; 3) accurate and quantitative measurement of the drug release.