Extractive Separation Of Sparingly Aqua-and Lipo-soluble Natural Bioacive Homologues With Ionic Liquids

Natural bioactive compounds (NBCs) are media molecular-weight compounds with complicated structure and multiple functional groups. A certain amoun of NBC molecules contain both hydrophobic and polar groups, and form strong intramolecular interactions, so their solubilities in aqua-and lipo-solvents are usually very low. Besides that, NBCs generally exist together with its their structural similar homologues in plants. As a result, the separation of the sparingly aqua-and lipo-soluble NBCs (SALS-NBCs) is quite challenging. Currently used separation methods, such as adsorption chromatography, suffer from large amount consumption of organic solvents consumption, low capacity, etc. Therefore, this dissertation intends to take the advantages of ionic liquid (IL), such as good dissolution power and the easiness to form liquid-liquid biphasic system, to establish an IL-based extractive separation method for the SALS-NBC homologues.The dissolution characteristics of typical SALS-NBCs in464ILs and58molecular solvents were predicted with the conductor-like screening model for realistic solvation (COSMO-RS) method. Based on the solvation interaction parameters, the relationship among NBC and/IL structures-interactions-solubility was investigated, and the molecular recognition mechanisms for IL-based separation of NBCs were explored. The results show that, multiple strong interactions are formed between NBC and IL molecules; The solubility of studied NBCs in ILs increases with increasing the hydrogen-bonding (HB) interaction strength, and ILs with high HB-basicity are able to selectively recognise the hydroxyl group difference of the NBC homologues through HB interaction.A new ternary biphasic system, IL-water-ethyl acetate, with low mutual solubilities was constructed. Factors that influence the phase equilibrium of this biphasic system were studied, including the structures of anion, cation and functional groups, molar ratio of IL to water, as well as temperature. The results reveal that ILs exhibit high ion solvation ability could greatly reduce the mutual solubilities of the biphasic system. As the concentration of IL increases, the dipolarity/polarizability of IL-water mixture decreases while the HB basicity increases.This IL-water-ethyl acetate biphasic system was applied to separate typical SALS-NBCs, including soybean isoflavone aglycones (flavone/structually differing in phenol group), ginkgolides (terpene/structually differing in hydroxyl group) and capsainoids (alkaloids/structually differing in carbon-carbon double bond). The relationship between IL structure and separation ability was studied, and the homologues were separated with high performance. The results show that, the distribution coefficients of soybean isoflavone aglycones are mainly determined by both the hydrophobic and HB interactions, while the selectivity of genistein to daidzein and glycitein is mostly dependent on the HB interaction; when1-(2-hydroethyl)-3-methylimidazolium chloride [HOEMIm]Cl-water mixture ([HOEMIm]C1/H2O=90/10, mol%) was used as extractant, the selectivity of daidzein and glyctitein to genistein are7.7and7.1, respectively. The distribution coefficients of ginkgolides and the selectivity of ginkgolide C (GC) to ginkgolide B (GB) are both enhanced as the HB basicity of IL-water mixture raises; the selectivity of ginkgolide A (GA) to GB, however, is maily controlled by both the dipolarity/polarizability and HB basicity of IL-water mixture; when N-ethyl-pyridinium bromide [EPy]Br-water mixture used as extractant ([EPy]Br:water=12.6:87.4, mole ratio), the selecticity of GA/GB and GC/GB reaches1.7and6.5, respectively, and meanwhile the capacity is as high as25.4g·L-1, more than10times larger than in traditional molecular solvent systems. In extractive separation of capsaicin homologues structually differing in double bond, the selectivity of capsaicin (caps) to dihydrocapsaicin (dhcaps) generally increases with the dipolarity/polarizability of extractant increases; when using aqueous N-methyl-N-ethylpiridinium bromide [PP12]JBr solution ([PP12]Br:water=10:90, mole ratio) as extractant, the selectivity of caps to dhcaps reaches2.1. In IL-water-ethyl acetate biphasic system with water as diluent, not only the amount of IL used and the viscosity of IL-rich phase are reduced, but also adequate distribution coefficients and relatively high selectivities could be obtained.Based on the extraction equilibrium study, multiple fractional extractions and reuse of IL were investigated. Adopting fractional extraction with8theoritial plates, the purity of target flavone compound genistein enhance from21.6to91.6%together with a recovery of91.6%, and the purity of target compound GB up to91.86%was obtained under separated operations. On the basis of diluent-swing effect, high performance back-extraction and IL regeneration method is estabilished, the IL’s separation efficiency is not influenced within5times reuse. Takeing ginkgolides separation for example, the IL-based extraction method could reduce organic solvents consumption for more than90%of used with traditional chromatography method. In conclusion, the IL-based extraction method is characterised by high selectivity, large extraction capacity, low organic solvents consumption and wide application.