Functional Supramolecular System Based On Cyclodextrin And Self-assembly Of Amphiphilic Peptide

In 1987, the Nobel Prize was awarded to Professor C. J. Pedersen, J. M. Lehn and D. J. Cram for their contribution to supramolucular chemistry. Since then, supramolecular chemistry has developed at a breathtaking pace and has gotten more and more attention. The major work in this field is about complicated and organized structures and function based on non-covalent interactions. In recent years, supramolecular chemistry has developed into an emerging interdisciplinary which colligated physics, informatics, material science and biotics closely.This thesis mainly concerned about supramolecular self-assembly, one of the most important area in supramolecular chemistry. Supramolecular self-assembly can provide novel structures and functional ordered aggregates which are of great significance for studying biological function and new materials. In 2005, the journal of Science has raised 25 major scientific questions that need to be solved in 21th century in its album of 125th anniversary, the only question related to chemistry is "How far can we push chemical self-assembly?" The theme of this dissertation is the self-assembly based on cyclodextrin or amphiphilic peptide using host-guest inclusion, hydrogen bonding and π-π packing as the main constructing strategy. This thesis mainly consists of 4 parts, including:Chapter 1 Introduction. The background, concept, property and driven force of supramolecular chemistry are introduced in this part. The important position and significance of supramolecular self-assembly are mainly discussed. Introduction of cyclodextrin and research progress of supramolecular self-assembly based on cyclodextrin. The backgrounds and significance of nanostructures constructed by the self-assembly of pepitides.Chapter 2 Novel vesicular systems based on P-cyclodextrin and ultra small organic molecules. Although there is plenty of work about the ratio, configuration and inclusion stability between cyclodextrin and ultra small organic molecules, few of them are related to the assembly morphology of the inclusion. For deeply understanding, we chose a series of organic molecules with different functional groups, studied the composition of the aromatic molecules and cyclodextrin in aqueous and found that the inclusion self-assembly the ordered vesicle structure. The structure was identified and characterized using various techniques. The structural factors that caused the self-assembly were also revealed. And we conclude that the basket-like dimmers formed by cyclodextrin through hydrogen-bonding interaction may be the driving force for the structures which is different from the typical cyclodextrin vesicles based on amphiphiles. In addition, the vesicular architecture could be endowed with a diverse range of stimuli-responses, as a consequence of the selective addition of various guest molecules.Chapter 3 Supramolecular self-assembly systems of cyclodextrin with amphiphiles. Amphiphiles are composed of hydrophilic and hydrophobic parts, which can self-assemble into mono-layer, membrane, micelle, vesicle or nanotube. With the addition of cyclodextrin into the sysytem, the formation of inclusion complexes would affect the original ordered structures and then cause changes in mophologies. The complex of an ionic liquid-based surfactant (1-hexadecyl) triphenylphosphonium bromide and β-cyclodextrin was studied. The morphology of the supramolecular aggregates was characterized and the mechanism of self assembly was proved. Influence of internal and external factors (molar concentration, inorganic salt, external molecules) was also investigated. We prepared the inclusion compound of β-cyclodextrin and an anti-inflammatory drug molecule fenspiride which possessed anti-allergic and anti-brochoconstrictive properties. The inclusion compound was characterized and the effect of cyclodextrin on the solubilization of fenspiride in aqueous solution was also studied. In addition, some drug molecules can self-assemble into various morphologies due to their molecular structures, and different assembled nanostructures may have different effects on blood circulation, intracellular transport and curative effect. So it is very important to control the self-assembly of drug molecules. The microaggregation of amphiphilic medicine molecule and the effect of cyclodextrin on medicine molecule in self assembly system were studied. The assembly and diaassembly of aggregation could be realized through the tuning of cyclodextrin and the catalysis of amylase.Chapter 4 Self-assembly based on amphiphilic peptide synthesized by coupling of cinnamic acid and glycylglycine. The common used method to construct amphiphilic peptides is by introducing hydrophobic groups to the end of the peptides through chemical reactions. The molecule could assemble into vesicular structure in aqueous solution through the π-π stacking of aromatic ring and the hydrogen bonding of dipeptides. The morphology of the vesicle was measured and the mechanism of the formation could be proved. Cnamate groups, which are photo responsive, can undergo two photoreaction pathways including trans-cis photoisomerization and photodimerization. Cinnamic acid and its derivatives are easier to prepare and the stability is higher than the other light-sensitive molecules (such as azobenzene, styrene, etc.). So the cinnamoyl photochemical reactions have great significance in the modification of polyers, liquid crystal display, responsive materials and natural products synthesis. Furthermore, we found the change of molecular configuration by UV-irradiation would influence assembly of the amphiphilic dipeptide, which realized the controlling of self-assembly aggregation.The innovated points of this thesis mainly include:(1) We develop a facile and general approach to construct vesicles based on cyclodextrin and ultra small organic molecules. This extends the variety and type of cyclodextrin vesicles. We demonstrate the critical role cyclodextrin played in the vesicles formation.(2) A novel system based on cyclodextrin and surfactant active ionic liquid was prepared. The self-assembly and transformation process in aqueous solution can be controlled by adjusting the factors such as concentration, temperature, pH and salt. And it is the first time to realize the transition from vesicles to hydrogels induced by salts in the cyclodextrin and surface active ionic liquid systems.(3) Preparation of the inclusion complex of cyclodextrin and fenspiride, a new kind of analgesic, anti-inflammatory, anti-allergic drugs in solution and solid state. And we first reported the assembly of cyclodextrin and amphiphilic drug molecules. The assembly and diaassembly of aggregation could be realized through the tuning of cyclodextrin and the catalysis of amylase.(4) A novel kind of amphiphilic dipeptide was succesfully synthesized. It is the first time to report the light-sensitive vesicles based on amphiphilic short peptide. Loading of pyrene as the hydrophobic model molecule into the vesicles was also carried out. To be mentioned, both cinnamic acid and glycylglycine are non-toxic organic molecules with good biocompatibility. The study can make contribution to the design of new drug delivery system.