Synthesis Of Novel Amphiphilic Steroid Derivatives And The Primary Study Of Their Self-assembly Behavior

Self-assembly of amphiphilic molecules can be used to create various nanostructures and it has experienced an enormous increase in interest over the last several years.The novel nanostructures with respect to self-assembly phenomena have numerous potential uses in biomimetic chemistry,material science,separation technology and pharmaceutical industries.Thus,it is necessary to study the formation and transition of amphiphile self-assemblies which would be helpful to the application in these areas.Steroid compounds are versatile building blocks which support both the architectures observed in biological systems and the formation of liquid crystal,bilayer membranes.These properties are basically related to the characteristics of the steroidal skeleton,the molecular rigidity,the aggregative nature and the asymmetric carbons. Glucosamine have many interesting properties such as intrinsic chiral property and biocompatible property.Furethermore,it has the multiple and directional hydroxyl groups that are able to participate in effective and strong hydrogen bonding to generate self-organized structures.In this study cholesterol and deoxycholic acid were hydrophilically modified by glucosamine and two new kinds of amphiphilic steroid derivatives were synthesized.Their self-assemblies were prepared through the sol-gel method and the ultrasonic emulsification-solvent diffusion method.The self-assembly behavior was investigated.The main study of this dissertation is shown as follows.1.Two new amphiphilic steroid derivatives(N-cholesteryl succinyl glucosamine, CSG and N-deoxycholyl glucosamine,DCG) were designed and synthesized.Their chemical structures have been confirmed by means of Fourier Transform Infrared Spectrometry(FT-IR),Nuclear Magnetic Resonance Spectrometry(NMR) and Mass Spectrometry(MS).These two compounds have not been reported in literature.2.Self-assembles of CSG and DCG were prepared through the sol-gel method. Their gelation abilities were evaluated in 16 organic solvents in this study.Our results have demonstrated that CSG could gelate 1-butanol,iso-butanol,4-heptanol, cyclohexanol and 1-octanol under the concentration of 5.0 mg/mL,but DCG can not gelate any of them.Scanning electron microscopy(SEM),transmission electron microscopy(TEM),circular dichroism(CD) and small-angle X-ray diffraction(SAXRD) were used to analyze the aggregation mode of CSG in the organogel phase.A hierarchical self-assembly model was proposed to explain the transition from molecular to primary and secondary structure.It is shown from our results that CSG can aggregate into a micellar fibril nanostructure with high length-to-width ratio which is bundled and entangled to form a three-dimensional(3D) network that immobilize the fluid component probably by surface tension.Moreover,sol-gel polymerization of tetraethoxysilane (TEOS) was carried out using CSG in the gel phase.The silica obtained from the CSG+ 1-butanol gel show the tubular structure with ca.100 nm outer diameters.3.A novel ultrasonic emulsification-solvent diffusion method was also used to prepare the nanoscale molecular assemblies of DCG and CSG.SEM,TEM,SAXRD and dynamic laser light scattering(DLLS) were used to characterized the aggregates of DCG and CSG.It was found that nanoparticles made from CSG showed a pH-dependent aggregation-disaggregation process.In pure water above pH4.7,the uniform dispersions of CSG were formed after sonication.It is shown that CSG aggregated into a micellar fibril nanostructure with high length-to-width ratio and these fibrils were bundled to form thicker fibers with diameters of 50-100nm.But in lower pH region((pH＜4.7),a great deal of white turbidity rapidly produced after sonication.It was considered that the intermolecular hydrogen-bond was broken in lower pH region.For DCG,the composition of the organic phase and the pH value of water have an important impact on the structure of DCG aggregates.When dimethylsulfoxide(DMSO) was used as the organic phase,a pH-sensitive micelle-to-vesicle transformation was observed.And the vesicles formed by DCG in acid region underwent a fusion process with the elapse of time.According to our knowledge,such self-assembly behavior of a bile acid based amphiphile has not yet been reported to date.The molecular packing theory and the classical Derjaguin-Landau-Verwey-Overbeek(DLVO) theory of colloidal stability were used to explain these phenomena.