Preparation Of Chiral Selectivity Functionalized Magnetic Particles And Their Applications

Chiral compounds are ubiquitous in nature and play a significant role in living bodies. The two enantiomers of chiral compounds possess disparate differences in their biological or physiological activities because of their different physical and chemical properties in living systems. Therefore, separation and recognition of chiral compounds is of great significance in life science and pharmaceutical clinical research. Most separation techniques, including chemical recognition, crystallization, membrane separation, enzyme resolution and chromatography, have been developed for chiral separation. Although these separation methodologies possess their own characteristics for chiral recognition, they generally require great amounts of chiral selectors, difficult separation process, expensive analysis cost, long separation time and complicated experiment operations. These unfavorable factors have limited their application in enantiomeric separations. Fabricating a simple, rapid and efficient separation technique becomes an important research focus in chiral separation fields.Recently, magnetic nanoparticles have attracted great interest because of their unique magnetic properties, superparamagnetism, nanometer-scale effects as well as excellent biocompatibility. These superior properties make them have been widely used in various fields such as biological medicine, environmental analysis, bioseparation and catalysis. In this work, a novel and facile analytical technique based on chiral selectivity functionalized magnetic particles was developed for chiral recognition. In order to increase the immobilization capacity of chiral selectors on magnetic beads and subsequently improve the efficiency of chiral separation, three kinds of magnetic materials including magnetic mesoporous microspheres, magnetic polymer microspheres and PAMAM-modified magnetc beads, were respectively prepared and were then used for the immobilization of macrocyclic antibiotic, β-cyclodextrin derivatives and protein chiral selectors to from different chiral selectivity functionalized magnetic particles. They were then effectively applied in direct chiral separation of a variety of racemic compounds. Combination of magnetic nanoparticles with functionalized chiral selectors was simple and high-efficiency for direct chiral separation of racemates. An external magnetic field can be applied to facilitate the separation of chiral selectors from racemic mixture and recycle them. This method provides a solid foundation for the online capillary electrophoresis chiral separation. Our main research work are listed in the following several aspects.(1) Fe3O4magnetic microspheres were used as supports and then coated with a thin silica layer. Magnetic mesoporous microspheres were prepared through a surfactant self-assembly method using cetyl trimethyl ammonium bromide (CTAB) as a template, which were then used for immobilization of macrocyclic antibiotics chiral selectors to fabricate the teicoplanin-modified magnetic mesoporous microspheres. The prepared magnetic mesoporous materials were regularly spherical with core-shell structures. They exhibited strong magnetic responsiveness and large specific surface area. Combing magnetic nanoparticles with mesoporous materials could remarkably improve the immobilization of teicoplanin on the surface of magnetic beads. These teicoplanin-functionalized chiral materials were effective in direct chiral separation of five racemic compounds and still remained good chiral recognition capabilities after they were reused five times. The results lay a solid foundation for preparation of various chiral selectivity functionalized magnetic beads and their subsequent application in chiral separation of different kinds of racemates.(2) β-cyclodextrin and its derivatives were powerful chiral selectors and could be employed for effectively separation of most chiral compounds. β-cyclodextrin derivatives possess stronger chiral recognition capability because of the additional recognition sites. Therefore, we developed a novel class of chiral selective magnetic materials based on imidazolium cationic-modified β-cyclodextrin derivatives for chiral separation. Vinylimidazolium-modified β-cyclodextrin derivative was synthesized starting from native P-cyclodextrin through a microwave-assisted synthesis process, and was then polymerized on the surface of magnetic beads to form the imidazolyl cationic P-cyclodextrin chloride-modified magnetic polymer microspheres. The synthesized chiral materials possess spherical structures, good dispersion and high magnetic responsiveness. They showed excellent chiral recognition abilities toward three dansyl amino acids, and can be readily separated from racemic solutions under an applied magnetic field.(3) Polyamidoamine dendrimer (PAMAM)-modified magnetic beads were prepared by microwave irradiation, and were directly used for the immobilization of HSA. The activity of the immobilized HSA and the biocompatibility of PAMAM-modified magnetic beads were evaluated by an immunoaffinity assay. These functionalized chiral materials were then applied in direct chiral recognition of three racemic compounds. The results show that the chiral recognition capability of HSA-functionalized magnetic beads was enhanced with increasing PAMAM generation. HSA immobilized on third-generation PAMAM-modified magnetic beads possessed excellent chiral separation capability and biocompatibility. The adoption of PAMAM significantly maximized the bonding of chiral selectors to carriers, which is an effective method for improving the chiral separation efficiency.