Ionic Liquids And Poly(ionic Liquid)s-based Separation Methods For Phosphatidylserine Purification

Homologues separation is a key process in the production of high-purity drugs and chemicals.High-purity phosphatidylserine(PS)is widely used as drugs and functional additives;however,PS often appears in a mixture with structurally similar homologues and the selective separation of phospholipid homologues remains challenging.Ionic liquids(ILs)have demonstrated great potential in the separations of structurally-related compounds due to their tunable structure and properties.In this thesis,the ILs-based liquid-liquid extraction experiments were selected as the method to obtain high-purity PS.Herein,we synthesized a series of mesoporous poly(ionic liquid)s(MPILs)and studied their adsorption capacity for phospholipid homologues.The solubilities of phospholipid homologues were determined.Based on the determination results,a series of IL/diluent-hexane biphasic systems were established to study their extraction performance for phospholipid homologues.Factors that influence the phase equilibrium of this biphasic system were investigated,including the diluent type,structures of ionic liquids,extraction temperature as well as initial concentration of the raw material.The results showed that the structure of the ILs'anion had a significant impact on the separation selectivity and Br-based ionic liquid exhibited excellent separation selectivity.In 1-ethyl-3-methylimidazolium bromide([EMIm]Br)/methanol-hexane biphasic systems,the selectivity of phosphatidylcholine(PC)to PS(SPC/PS)reached up to 29.48,when the mole fraction of IL was only 5%,which revealed significantly better property than that in traditional solvent systems.Increasing the length of the alkyl side chain on the cation had a great impact on the distribution coefficients of PC(DPC).When the alkyl side chain on the cation was extended from ethyl([EMIm]Br)to octyl([OMIm]Br),the DPC increased from 11.79 to 37.11.Additionally,we found that an obvious synergistic extraction effect between IL and polar diluent was observed.Based on the extraction equilibrium study,ab initio calculations and dynamic light scattering were used to explore the micro-interaction and micro-structure between ionic liquid and phospholipid homologues.It was found that phospholipid homologues formed multiple hydrogen-bonding and electrostatic interactions with IL.Thereinto,the P=O group of PC formed triple hydrogen bonds with the H atoms of[EMIm]Br,and multiple H atoms of the quaternary amine structure of PC had a strong electrostatic interaction with the anion Br of[EMIm]Br.The interactions of hydrogen-bonding and electrostatic between PC and[EMIm]Br were stronger than those between PS and[EMIm]Br.On the other hand,the interaction energy between PC or PS and[EMIm]Br by ab initio calculations were obtained.The value of the interaction energy between PC and[EMIm]Br was-129.45 kJ/mol,which was larger than the value of the interaction energy between PS and[EMIm]Br(-91.70 kJ/mol),indicating that[EMIm]Br has a stronger recognition to PC,which is probably beneficial for the selective separation of phospholipid homologues.Seven kinds of porous poly(ionic liquid)s(PILs)with different alkyl side chains on the cation based on 3-alkyl-1-vinylimidazolium bromide monomer were synthesized by cross-linking polymerization.The structure,morphology,ionic liquid content and thermal stability of PILs were characterized by specific surface area,SEM,FT-IR,elemental analysis and TGA.The results indicated that the synthesized PILs were mesoporous materials,and the thermal stability of PILs increased with the increasing ionic liquid content of PILs.The adsorption properties of mesoporous polyionic liquids for phospholipid homologues were investigated.It showed that increasing the alkyl side chain length of imidazolium bromide of PILs and reducing of the proportion of crosslinker were beneficial to improve the adsorption performance of the PILs for the phospholipid homologues.P(2DVB-OVIMBr),which was synthesized by[OMIm]Br and DVB at a molar ratio of 2:1,exhibited high adsorption capacity for phospholipid homologues.The adsorption capacity of P(2DVB-OVIMBr)to PS,PC and phosphotidylethanolamin(PE)could reach to 17.05,7.58 and 7.20 mg·g-1,which can achieve the selective adsorption.In addition,the adsorption kinetics of phospholipid homologues adsorbed on mesoporous PILs were studied.It was found that their kinetic curves could be fitted with Lagergren first order rate equation.