Preparation And Application Of Gold-Functionalized Silica-Based Chiral Columns For High-Performance Liquid Chromatograpy

The enantiomers of chiral drugs have great differences in pharmacological aspects, so the separation of enantiomers has attracted much more attention. High performance liquid chromatography (HPLC) method is widely used in enantioseparation, because of its high efficiency, rapid and accurate. In order to increase the types of chiral stationary phases (CSP), achieve higher enantioseparation efficency and selectivity of traditional silica-based HPLC, and overcome unavoidable weakness of silica from low mechanical strength, specific surface area and the sample capacity, in this paper, nanoparticles will be introducted into the traditional stationary phases, to research and develop a kind of novel chiral stationary phase for the corresponding chiral drug enantiomers separation. This paper includes three sections as the following:(1) Based on chloroauric acid used as raw material, monodisperse gold nanoparticles (Au NPs) with diameters of 15±5nm were synthesized through chemical reduction method. The SiO2@Au core-shell material was fabricated by the seed growth method. The resulting material of SiO2@Au possessed a core-shell structure in which AuNPs were the shell and silica spheres were the core. In addition, through studying on synthetic conditions in detail, it was found that the proportion of reducing agent and the amount of Au NPs had an impact on the formation of Au shell. Then SiO2@Au core-shell materials were prepared under the optimized conditions. The SiO2@Au-3,5-dimethyl-phenyl isocyanate derivative of cellulose CSP was prepared by coating 3,5-dimethyl-phenyl isocyanate derivative of cellulose on the surfaces of SiO2@Au core-shell materials, and was applied to separate chiral compounds. The experiments revealed that the separations of nine pairs of enantiomers (flavanone (Rs=1.10), ibuprofen (Rs=2.20), fenthion (Rs=1.20) etc.) were achieved by SiO2@Au-3,5-dime-thylphenyl isocyanate derivative of cellulose chiral stationary phase under the normal chromatographic mode, respectively. The CSP based on SiO2@Au exhibited a higher mass transfer rate, compared to the corresponding SiO2-3,5-dimethyl-phenyl isocyanate derivative of cellulose column.(2) A novel chiral stationary phase of SiO2@Au-thiol-β-cyclodextrin (SH-β-CD) was prepared through bonding chemically SH-β-CD on the surface of the SiO2@Au core-shell material, and then the chromatographic performance was evaluated. It is concluded that nine compounds (propranolol (Rs=3.67), flavanone (Rs=1.47), diazinon (Rs=1.18) etc.) have a good separation. The effects of mobile phase, salt concentration, pH value and column temperature on the separation of racemates were investigated. Compared with traditional cyclodextrin CSP, the new CSP showed a higher mass transfer rate and special selective for investigated analytes due to the surface effect of Au NPs, which showed that chiral-modified AuNPs on the surface of silica gel had more sufficient interaction with the analytes, resulting in significant enhancement of enantioseparation efficiciency.(3) SiO2 nanoparticles were prepared by sol-gel method based on tetraethylorthosilicate. The SiO2@SiO2 core-shell material was formed based on self-assembly of SiO2 nanoparticles (NPs) on the surfaces of porous silica spheres under mild conditions. The SiO2@SiO2-3,5-dimethyl-phenyl isocyanate derivative of cellulose CSP was prepared by the coating method and then evaluated the chromatographic performance was evaluated. The results showed that 13 racemates (cypermethrin, flavanone, pirimiphos-methyl etc.) could be effectively separated.