Synthesis And The Self-Assembly Of Functional Supramolecular Systems

In1987, the Nobel prize was awarded to3scientists:C. J. Pedersen, J. M. Lehn and D. J. Cram to commend their pioneering contribution on the theory and application in supramolecular chemistry. Since then, supramolecular chemistry, as a new frontier subjects, has been rapidly developed. Supramolecular chemistry has drawn much attention by scientists and merged into every area of chemistry, even science, with much contribution. Then in2005, among the25questions to be urgently resolved in21st century were proposed by the famous journal "Science" in its125anniversaries special volume, the only one relative with chemistry is "How far can we push chemical assembly?", from which it is known that chemical assembly is the key question in the research of supramolecular chemistry.Literally, supramolecular chemistry can be defined as "chemistry beyond molecules", which means the holistic chemistry with highly complicated and organized properties constructed by several chemical species through the interactions between molecules, including the hydrogen bonding, host-guest interactions, hydrophobic-hydrophobic interaction, electrostatic interactions and π-π stacking, etc. Since the parts are not connected by the covalent bonds, they can still maintain some connatural physical and chemical properties and show the monolithic function for the interactions between each other.At present, supramolecular chemistry has already colligated biology, material science and physics to construct "supramolecular science" and "supramolecular technology". The obvious achievement of supramolecular science is to direct the information science with organized, complicated and adaptive exhibitions, from inorganic to zoetic. The field develops so fast that even the relative scientists pause to ponder and bring forward:"Supramolecular Science:Where It Is and Where It Is Going?", which is also the subject of the last supramolecular chemistry conference before21century (1998). Prof. J. M. Lehn, the father of supramolecular chemistry, ever advanced3subjects:information and programmability, dynamics and reversibility&combinatorial feature and adaptability.Synchronously, supramolecular chemistry is also an important field in researching the bio-function, understanding the life phenomenon and exploring the life origin. Supramolecular chemistry is also an area that develops very fast and full of energy. The essence of this interdisciplinary subject has attracted the comprehensive attention of physicists, theory scientists, crystal scientists, inorganic solid chemists, organic synthesis chemists, biochemists and biologists.This thesis mainly concerned about supramolecular self-assemble, the most important area in supramolecular chemistry. Self-assemble phenomenon is very common in our daily life, for example, the formation of the galaxy, cloud or minerals, the growth of plants, the construction of organelles. It is so normal, and if we can function and control the self-assemble behavior, some unexpected effects may be obtained, which could have great impact to the present chemistry even science, whose research objects are mainly materials connected by covalent bonds. Supramolecular functional self-assemble will break the long-time "monopolize" of synthetic chemistry based on the covalent bonds, especially in material science. In a word, supramolecular functional self-assemble is a great challenge and an area waiting to be deeply studied.This thesis mainly consists of6parts, including:(1) Cyclodextrin, as a nanoreactor with excellent properties, has been widely applied in the mimic of the bio-enzyme. Firstly, we developed a novel synthesis method for the preparation of benzofurazan-N-oxides:in the neutral aqueous solution at room temperature, o-nitroaniline was oxidized under supramolecular catalysis by cyclodextrins. Cyclodextrins can be easily recovered by filtration and reused for the consecutive runs in this reaction without almost no change in the yield and purity. Based on the comparison of the1H NMR and FT-IR experimental results, the reaction mechanism was proposed. Cyclodextrin and o-nitroaniline can form a special supramolecular inclusion through hydrogen bonding and hydrophobic-hydrophobic interaction. Cyclodextrins play a role of supramolecular phase-transfer catalyst. What's more, the cavity of cyclodextrin and the hydrogen bonding would protect the obtained benzofurazan-N-oxides from the over-oxidation. From the supramolecular inclusion, we can recognize the key role of the supramolecular functional self-assemble plays. In a word, the traditional base and acid&the organic solvents were excluded. A new synthesis approach for the preparation of benzofurazan-N-oxides was advanced through a green method. Secondly, the traditional Beirut reaction was greatly improved to approach green chemistry. Beirut reaction was carried out in the aqueous medium with excellent yield. Cyclodextrins can be easily recovered and reused for the consecutive runs in this reaction without decrease in the catalysis property. Based on the comparison of the1H NMR and FT-IR experimental results, the reaction mechanism was proposed. The avoid of the organic solvents can elude the explosion danger, which is a practical routine. In the field of supramolecular catalysis, the "covalent effect" was firstly proposed.(2) A novel class of surfactant-"supramolecular surfactant" was designed, prepared, characterized and applied. The strategy was demonstrated as follows:in order to achieve the goal, nine n-AQs with different lengths of alkyl were synthesized by the direct reaction of1-nitroanthraquinone and alkylamines to act as the guest molecules. With the inclusion of n-AQ and β-CD, the supramolecular complex can self-assemble into vesicular structures in the methanol/water solvent, which were visualized by TEM, SEM, DLS and EFM. The property of fluorescence was successfully implanted into vesicles, which was observed by EFM. The possible mechanism of the vesicle formation was suggested based on the results of UV, fluorescence spectrum and MD simulation. The vesicles were sensitive and multi-responsive to external stimuli. Furthermore, the vesicles were successfully applied in the staining of living cells and the possible staining approach was also suggested. We believe that the supramolecular vesicles will serve useful in the fields of biomaterials, cell-mimic, design of intelligent materials and molecule machines.(3) In summary, we report the preparation and application of the first pH-reversible fluorescent vesicle system based on the "supramolecular amphiphiles". With the inclusion of the guest molecule and cyclodextrin, the supramolecular complex can self-assembly into vesicular structures in aqueous solution, which were revealed by TEM, SEM, DLS and EFM. The possible mechanism of vesicle-formation was suggested based on the results of1H NMR,2D NMR ROESY, UV, and FT-IR. The vesicles collapse when acetic acid was added. When pH was adjusted to7.0, vesicles appeared again. The vesicles were successfully applied in the staining of living cells and the possible staining approach was also suggested. We believe the supramolecular vesicles will serve useful in the fields of biomaterials, cell-mimic, design of intelligent materials and molecule machines.(4) In summary, we constructed the supramolecular nanorod aggregation in aqueous solution from the special amphiphile composed of a conjunction of cyclodextrin and anthraquinone. The nanorods transform into vesicles upon the introduction of cyclodextrin, which acts as a dissociation agent for the π-π stacking. The possible mechanisms of the formation of the nanorods and vesicles are suggested based on the results of TEM, SEM, DLS, EFM, UV-vis, and2D NMR ROESY. The vesicles are responsive to Cu2+/H+. Understanding the cyclodextrin-linked-anthraquinone system may hopefully provide a sophisticated pathway for the design of intelligent materials with high sensitivity and selectivity. We believe the supramolecular system will also be useful in the fields of biomaterials and cell mimicry.(5) A facial approach to design vesicles with functional macrocyclic host sites was developed:a modified cyclomaltoheptaose (P-cyclodextrin) containing an anthraquinone moiety, was synthesized via3steps. In aqueous solution the conjuction can self-assemble into vesicles, which was characterized in detail by TEM, SEM, EFM and DLS. The possible vesicular model with functional host sites on the bilayers was suggested and demonstrated based on the result of2D NMR ROESY, UV-vis spectrum and MD simulations. The vesicles are responsive to the external stimuli, such as H+and Cu2+. With macrocyclic host sites confined on the bilayers, the vesicles could carry PTX effectively via the recognition of cyclodextrin. The loading mechanism was given based on the1H NMR,2D NMR ROESY, FT-IR and XRD results. The vesicles coated with PTX have remarkable anticancer effects, even better than natural PTX. We believe this work will cast a new light on the delivery materials with macrocyclic host sites.(6) Three azobenzene caged-compounds based on naphthalene were synthesized and the process was optimized. The structure-function of this class of compounds was researched and we found that if the azo connected at the a site of the naphthalene, the energy to excitate the molecule can be diminished, further to decrease the energy of the light for the configuration inversion. The wavelength of the excitation light was successfully moved to the visible light area, and correspondingly, the needed energy was decreased to a great extent, which will expand the application of this class of compounds in the biological area. The introduction of sulfonic acid greatly increased the solubility in aqueous solution. Basically, this kind of compounds can be controlled by the visible light in aqueous solution.The innovated points of this thesis mainly includes:(1) The traditional reactions in organic solvents was successfully carried out in aqueous medium under the supramolecular catalysis. The reaction condition was greatly optimized and the catalysts can be recycled, which can be fit to the demand of green chemistry. This point is especially important at present for the deficiency of energy and resources. Based on the above, the "covalent effect" was firstly proposed.(2) Novel sensitive vesicular system based on the "supramolecular surfactant" was studied, including the design of the guest molecules, the preparation and characterization of the vesicles, the proposing and confirmation of the mechanism and the application in the living-cell-staining area.(3) PH-reversible vesicles based on the "supramolecular surfactant" were firstly studied. The morphology was fully characterized by multiple methods. The vesicle-formation and pH-reversible mechanisms were suggested. The system was successfully applied in the area of the staining of the cancer cells. The vesicular system may have further application in the load and targeted release of the anti-cancer drugs.(4) The cyclodextrin-anthraquinone conjunction was synthesized and its self-assembling behavior in aqueous solution was studied:at room temperature the conjunction can self-assemble into well-defined nanorods and transform into vesicles induced by the external natural cyclodextrin. The study will provide new references in the field of preparation of controlled materials and the design of molecular machines.(5) Another cyclodextrin-anthraquinone conjunction was synthesized and its self-assembled behavior in aqueous solution was studied. The assembled vesicles and the mechanism were fully characterized. We successfully loaded hydrophobic paclitaxel to the vesicle system. The paclitaxel-loaded-vesicles were found to have excellent anti-cancer effect. This will cast a new light in the design of novel drug carrier systems.(6) New photo-controlled caged compounds were synthesized, which greatly improve the property of the system with photo-controlled release protons. The energy to excitate the molecule can be diminished, further to decrease the energy of the light for the configuration inversion. The wavelength of the excitation light was successfully moved to the visible light area. The introduction of sulfonic acid greatly increased the solubility in aqueous solution. The formal acetonitrile solvent was excluded. The research will greatly expand the application in the biological areas.