Nordihydroguaiaretic Acid Surface Molecularly Imprinted Polymers:Preparation,Recongnition And Characteristics

Nordihydroguaiaretic acid (NDGA) belongs to the lignans compounds, and widely exists in larrea tridentate, guaiacum officinale, yucca, ephedra and other plants. NDGA is a kind of phytoestrogen, and can remove free radicals, antioxidant, antibacterial, antiviral, antitumor and other pharmacological activities. In recent years, researcher found that NDGA can inhibits breast cancer, liver cancer, lung cancer, colorectal cancer, glioma tumor and have the ability to inhibit the proliferation and metastasis of cancer cells. NDGA extraction from natural medicine was found no significant side effects through animal experiment. So producing drugs for the treatment of tumors by NDGA has important practical significance and broad application prospects.Molecular imprinting technology (MIT) formed the template molecular complexes under the effect of one or more functional monomers, and then through the initiator polymerization between functional monomers and crosslinking agent. The obtained polymers after removing the template molecules by chemical or solvent extraction can be molecularly imprinted polymers (MIPs) with certain hole structures and recognition sites. In this thesis, it is that the computer molecular simulation as a theoretical guidance, the surface molecular imprinting technology was adopted to synthesize NDGA molecularly imprinted polymers, structure characterization and adsorption study. The research detail contents include the following four parts:In the first part, the development and principles of molecular imprinting technique, the preparations, synthesis methods and applications etc. of MIPs are summarized, meanwhile the research background, signification, technical route, content of meaning and highlight of this research are described.In the second part, the experiment method, experiment steps, experiment content as well as the medicine and reagent, instruments using in the experiment are described in detail.In the third part, the experimental data and, experimental result, analysis and discussion of the research are presented and the main points are as follows:(1) the selection of the optimum solvent, functional monomer, the ratio of the template molecules and functional monomer. The results show that in the molecularly imprinted pre-assembled system, when ethanol as the solvent, the solvation energies of both NDGA and functional monomer y-aminopropyltriethoxysilane (APTS) are the best, meanwhile, the complex in which the molar ratio of NDGA and APTS is 1:4 has a higher stable binding energy.(2) Design experiment method by orthogonal, optimize the experimental conditions. The optimum synthesis conditions of the NDGA molecularly imprinted polymers (MIP@SiO2) are as follows:NDGA as the template molecule, APTS and methyltriethoxysilane (MTEOS) as the functional monomers, tetraethyl orthosilicate (TEOS) as the cross-linker and ethanol as the porogenic solvent in the surface of silica. In addition, the optimum adsorption affinity occurred when the molar ratio of NDGA:APTS:MTEOS:TEOS was 1:6:2:80.(3) Scanning electron micrographs show that the surfaces of MIP@SiO2 particles became rough and scraggy, which was caused by the cladding and filling actions of the crosslinking polymer layers which was formed in the process of NDGA surface imprinting. Infrared spectra show that further demonstrating that template molecules (NDGA) were successfully removed from the surface of silica gel. Thermogravimetric analyses indicated that NDGA grew on the surface of silica gel. Nitrogen adsorption-desorption analysis demonstrated that the MIP@SiO2 layer was formed on the surface of silica gel successfully, and the entrance of mesoporous had been blocked.(4) The adsorption condition and properties of MIPs@SiO2 were studied. The optimum solid-liquid ratio experiments show that the solid-liquid ratio of 10/10 (w/v, mg/mL) adsorption capacity is the largest. Optimal pH experiments show that the pH value of eight can reach the largest adsorption capacity. The static adsorption experiments and dynamic adsorption experiments showed that the surface imprinting polymer adsorption balance (5.90 mg g-1) when the initial concentration of NDGA was 0.04 mg mL-1, and oscillation adsorption 8 h. Selective adsorption experiments show that the NDGA-MIP@SiO2 has higher dissociation constant Kd (147.50 mL g-1) for NDGA, separation factor a (5.62 and 1.82) and selective factor β (3.09).In the reusability analyses, the molecularly imprinted polymer repeat utilization rate remained at 90%. The results clearly showed that the MIP@SiO2 could be used repeatedly without distinctly losing its adsorption amount.(5) According to the MIP@SiO2 and NIP@SiO2 for ephedra ethanol extract of NDGA adsorption experiment. The adsorption capacity of MIP@SiO2 and NIP@SiO2 are 4.90 mg g-1 and 1.70 mg g-1 respectively, and the imprint factor (y) was 2.88, which implied that MIP@SiO2 was of good selectivity to NDGA.In the fourth part, the research results of the thesis are summarized, and the development directions of molecular imprinting technique in the future are also forecasted.