Preparation Of Molecularly Imprinted Polymer For Artemisinin Based On The Surface Of Silica Gel And Its Adsorption And Separation Behaviour In Supercritical Carbon Dioxide

Artemisinin is an effective antimalarial drug isolated from the herbal medicine Artemisia annua L. It is recommended to treat malaria by World Health Organization (WHO).Molecularly imprinted polymer is a kind of adsorbent with the ability of specifically recognizing and binding the target molecules. The surface molecular imprinting technique can decrease the steric hindrance between recognition sites and target molecules by designing the molecular recognition sites on the surfaces of imprinted materials. In the conventional organic solvents, though good separation can be achieved by imprinted polymers, the time to reach adsorption equilibrium is long and the adsorption capacity is also limited. In addition, the organic solvents are not good for environment. Supercritical CO2 has good solubility for artemisinin and high diffusion ability, but it has not excellent selectivity for analogues. If imprinted polymers are employed in supercritical CO2 instead of organic solvents, the mass transfer rate and adsorption capcity should be impoved. Combination of molecular imprinting technique and supercritical technology is a promising and environment-friendly method with prospects of sustainable development.In this paper, the preparation process of molecularly imprinted polymers (MIPs) for artemisinin was introduced. Silica gel (40-60mesh) were used as supporting matrix, and vinyltriethoxysilane (VTES) was grafted onto its surfaces. The preparation of MIPs for artemisinin was performed on the surfaces of the modified silica gel using artemisinin as the template, acrylamide (AM) and methacrylic acid (MAA) as the functional monomers and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. Elementary analysis, scanning electron microscopy, Fourier transform infrared spectroscopy and pore size analysis were used to characterize the prepared MIPs. The results showed that the imprinted film was coated onto the surfaces of silica gel. The surface area of MIPs was 325.042m2/g and pore size was 83.013?.Under the normal temperature and pressure condition, the adsorption and separation behaviour was measured in toluene solvent. The adsorption reached equilibrium at about 10h, while fast adsorption took place during the first 2h. Pseudo-first-order, Pseudo-second-order and Elovich adsorption kinetic equations were used to correlate the experimental data of the adsorption kinetics, and pseudo-second-order equation had the best correlation (R2=0.9730). At varied initial concentrations of artemisinin (range from 0.20mg/mL to 2.00mg/mL), adsorption capcity of MIPs and NIPs (non-imprinted polymers) both increased with the initial concentration of artemisinin, but MIPs had much higher adsorption capcity than that of NIPs. The adsorption capcity was 32.44mg/g at an initial artemisinin concentration of 2.00mg/mL. Langmuir, Freundlich and Langmuir-Freundlich isotherms were used to correlate the experimental data of the adsorption isotherm, and Langmuir-Freundlich isotherm had the best correlation (R2=0.9953). The selectivity coefficient of MIPs for artemisinin was 2.29 in artemisinin/artemether mixed solution with the initial concentration of 2mg/mL of each substance, and the relative selectivity coefficient was 2.03. The selectivity coefficients of MIPs for artemisinin with respect to artemether and arteether were 2.88 and 3.38 in artemisinin/artemether/arteether mixed solution with the initial concentration of 2mg/mL of each substance, and the relative selectivity coefficients were 2.74 and 3.10, respectively.A supercritical apparatus with a video detection window was applied in the observation of the process of artemisinin dissolved in supercritical CO2 and the determination of artemisinin solubility in supercritical CO2 at 313K (11～31MPa),323K (14～31MPa),333K (16～31MPa) by static method. The range of experimental solubility data was from 0.498×10-3 to 2.915×10-3mol/mol. At a fixed temperature, the solubility of artemisinin in supercritical CO2 increases with the pressure. At a fixed pressure, the effect of temperature on the solubility shifts from negative at the pressures below the crossover region to positive at the pressures above the crossover region. Chrastil and Mendez-Santiago-Teja models were selected to correlate the experimental solubility data. The average absolute relative deviation of the two correlations was 8.32% and 8.33%, respectively, which showed the good agreement between calculated values and experimental values. The relative deviation will be smaller when the experimental conditions are far away from the critical point.Under the 313K,20MPa condition, the adsorption and separation behaviour was measured in supercritical CO2. The adsorption reached equilibrium at about 3h, while fast adsorption took place during the first 0.5～1h. Pseudo-first-order and Pseudo-second-order adsorption kinetic equations were used to fit the experimental data, and pseudo-second-order equation had the better correlation (R2=0.9936). Adsorption capcity of MIPs for artemisinin increased with the initial concentration of artemisinin, and the adsorption capcity was 123.89mg/g at an initial artemisinin concentration of 1.74mg/mL. The selectivity coefficient of MIPs for artemisinin was 3.29 in artemisinin/artemether mixed solution with the initial concentration of 1.94mg/mL of each substance.Under the experimental conditions, adsorption equilibrium time in supercritical CO2 was less than 1/3 of that in toluene, adsorption capcity of MIPs in supercritical CO2 was as 4 times as that in toluene, and the selectivity coefficient of MIPs in supercritical CO2 increased when compared with that in toluene.