The Synthesis Of Novel Imidazolium-based Biomimetic Ionic Liquids And Applications In Their Separation Of Drug Molecules

Ionic liquids are attracting extensive attention of many scientists due to their unique physicochemical properties, such as low vapor pressure, good thermal stability, strong dissolving ability and designed property. With the rapid development of functionalized ionic liquids, the functionalizations of ionic liquid always cause the increasing of melting point and viscosity, which will restrict the application of the functionalized ionic liquids. Therefore, the designs and synthesizes of low melting point and viscosity of biocompatible biomimetic ionic liquids are of great significance. As a part of the project supported by the National Nature Science Foundation of China(Nos. 21173070, 21303044), seven novel biomimetic ionic liquids were synthesized by introducing the unsaturated and kinked tails into the side alkyl chain of alkylimidazolium ionic liquids. The biomimetic ionic liquids were applied to the separation of drugs. The major contents are as follow:1. Novel imidazolium-based biomimetic ionic liquids were synthesized: [C6(2)mim]BF4, [C6(2)mim]PF6, [C10(3,7)mim]Cl, [C10(3,7z)mim]Cl, [C10(3,7)mim]CH3COO, [C10(3,7z)mim]CH3COO and [C10(3z,7z)mim]PF6. These ionic liquids have different anions, such as chlorine ion, acetate radical ion, tetrafluoroborate ion and hexafluorophosphate ion. These ionic liquids have been characterized by NMR, TGA and DSC. The novel biomimetic ionic liquids(except [C10(3z,7z)mim]PF6) are liquid at room temperature. These ionic liquids with low melting point exhibit excellent thermostability.2. The data of the tie line were determined for aqueous two-phase systems(ATPSs) based on the ionic liquid 1-octyl-3-methylimidazolium bromide([C8mim]Br) and inorganic salts(K2HPO4, K3PO4, K2CO3) at 298.15 K. The abilities of three salts on the formation of the ionic liquid-ATPSs have been investigated. On the basis of the data of the tie line, [C8mim]Br-K2HPO4 ATPS were selected to separate pyritinol hydrochloride(PHC). The effects of the concentrations of ionic liquid or inorganic salt, temperature and the addition of micro biomimetic ionic liquids on the partition of PHC were investigated systematically. The dynamic light scattering(DLS) and UV-Vis spectrophotometry were used to investigate the partition behavior and the possible partition mechanism of PHC in both phases. The results indicated that extraction efficiency of PHC was improved when hydrophobic ionic liquids were added in the ionic liquid-ATPS. Hydrophobic ionic liquids [C10mim]BF4 and PHC interactions with [C8mim]Br promoted the transfer of drug molecules from the bottom phase to the top phase in ionic-liquid-based ATPS.3. The distribution behaviors of three drugs(PHC, dopamine hydrochloride and acetyl amino phenol) in these systems composed of the hydrophobic biomimetic ionic liquids and water were also studied. The effects of molecular structures of drugs and ionic liquids, temperature on the separation of the drugs were examined systematically. Experimental results showed that the biomimetic ionic liquids with the unsaturated and kinked tails had a larger volume, hinder ionic liquids interaction with drug molecules, and thus the extraction performance of drug molecules was reduced. The transfer of drug molecules from water phase to ionic liquid phase is a spontaneous process in liquid liquid extraction system. Moreover, raising the temperature is beneficial to the extraction of drug molecules.