Preparation And Application Of Novel High Performance Liquid Chromatography Chiral Stationary Phase Based On Graphene Oxide

Chiral phenomena and chiral drugs have always been the research hotspots in the chemical and biological fields.Therefore,higher requirements have been put forward for the development and separation of racemates in clinical drug substances.In order to obtain further the pure single enantiomer and the respective metabolic processes of the two enantiomers,it is necessary to develop the efficient chiral separation materials to separate increasingly complex racemates with the different properties and structures.In recent years,with the rise of nanomaterials,the physicochemical properties of graphene oxide(GO)have been gradually discovered and formed into composite materials for biosensors,solar cells,adsorption separation,catalysts and other fields.As a simple separation method,high performance liquid chromatography(HPLC)has the advantages of qualitative and quantitative analysis and trace amount determination,which can meet the requirements of enantioseparation and determination under complex conditions.Based on the previous related research,we prepared a series of HPLC chiral stationary phases(CSP)by bonding GO to Si02 and adding different chiral selector to apply iin enantioseparation.The main work in the study is as follows:here are four main aspects.(1)The GO was chemically bonded to NH2-SiO2 to obtain GO@SiO2,and further reduction to obtain rGO@SiO2.Cellulose-tris(3,5-dimethylphenylcarbamate)as a chiral recognition material was coated to rGO@SiO2 to obtained cellulose derivatives CSP and for the separation of chiral enantiomers.The results show that the presence of rGO significantly increased the hydrophobic interaction and ?-?stacking of CSP material with chiral drugs compared to blank columns,and the retention time and resolution increased significantly.The rGO and cellulose derivatives have a synergistic effect on enantioseparation.Nine aromatic chiral compounds were separated and cellulose derivatives chiral column was stable with a special range of temperatures.(2)?-CD-GO@SiO2 type CSP was prepared by using GO@SiO2 as matrix and ?-cyclodextrin(?-CD)as chiral recognition material.Seven chiral substances were separated with different degrees in reversed-phase chromatography mode.A mixture of four nucleoside with small molecules were separated in the hydrophilic interaction chromatography(HILIC)mode on this CSP.The separation sequence is closely related to the molecular structure and polarity of analytes.The separation mechanism of analytes on the CSP were discussed in depth by investigating the influence of retention time with the composition,temperature and pH of mobile phase.CSP promotes enantioseparation of analytes by hydrogen bonding,?-? stacking and so on.GO and p-CD have a synergistic effect on enantioseparation.The retention and separation of nucleoside molecules in HILIC is due to the interaction of multiple forces.(3)Van-GO@SiO2 type CSP was prepared by using GO@SiO2 as matrix and vancomycin derivatives as a chiral recognition material.Seven chiral substances were evaluated for enantioseparation ability in the normal phase or reversed phase mode on the CSP,and retention properties were further investigated.The results show that the novel vancomycin chiral column exhibits certain enantioseparation ability in both normal and reversed phase modes due to the presence of GO and synergistic effect with vancomycin in enantioseparation.Through studying the effect of column temperature on the enantiosepatation,it was further found that the vancomycin chiral column has good stability in the experimental temperature range and the temperature change does not affect its separation mechanism.(4)A GO@Zn-MOF type CSP was prepared based on metal organic framework(MOF)and GO.Nine chiral substances were separated on this CSP with a mobile phase including n-hexane at least 90%.1-phenylethanol were used as a test probe to investigate the effect of temperature and flow rate on the enantiosepartion.The physical and chemical properties of GO and the pore effect of Zn-MOF have a significant impact on the resolution of chiral substances.According to the relevant literature data and the comparison of this study,some analytes were separated on the surfaces of the Zn-MOF material by chiral recognition and GO interaction,meanwhile the otherswere separated by the pore effect and chiral recognition via the Zn-MOF channel.