Preparation And Chiral Separation Properties Of Cellulose Derivative/Silica-Based Hybrid Materials

Due to the importance of enantiomers with optical activity in biology,medicine,life science and other fields,the preparation methods and mechanism of optical pure enantiomers have attracted great attention in many fields.How to obtain enantiomer drugs has become a research hotspot.Chiral stationary phases(CSPs)based on cellulose derivatives for high performance liquid chromatography(HPLC)have been widely used due to their high-efficiency chiral recognition performance.Until now,the content of organic components in the commonly used chiral stationary phase of cellulose does not exceed 20 wt%.This feature greatly limits the development of chiral stationary phases with high-efficiency chiral separation performance.Based on this background,a series of organic-inorganic hybrid materials with high organic contents using cellulose derivatives as organic matrix and tetraethyl silicate(TEOS)as inorganic silicon source had been prepared through acid-catalysed and base-catalysed sol-gel processes,respectively.The reaction process and preparation conditions were systematically investigated,and the preparation mechanism and chiral recognition mechanism of the obtained hybrid materials were further explored.Cellulose tris(3,5-dimethylphenylcarbamate)derivatives containing 0%,2% and 4% of 3-(triethoxysilyl)propyl group were synthesized by carbamoylation method based on microcrystalline cellulose,respectively.The structure of the synthesized derivatives is regular and the substitution is complete.A series of organic-inorganic hybrid materials with high cellulose derivative content was prepared by acid catalysis sol-gel method.The hybrid materials have regular morphologies,uniform particle size distribution,large specific surface area and narrow pore size distribution.And the organic contents are higher than 30 wt%.Among them,the type of surfactant and alcohol have important effects on the synthesis efficiency of acid catalysis method and the properties of hybrid materials.Using cationic surfactants and alcohols with long alkyl chain can significantly increase the yield of hybrid materials,and the particle size of hybrid microspheres decreases with the increase of surfactant concentration.AC-6,AC-9 and AC-12 have excellent chiral recognition abilities,all the racemates except Rac-6 have good separation results.The chiral separation results of Rac-1 and Rac-4 on the acid-catalyzed hybrid materials AC-6,AC-9 and AC-12 were better than those on commercial column Chiralpak IB.The chiral separation ability of the hybrid chiral packing materials was much dependent on the organic content,and the higher the organic content,the better the chiral separation ability.The hybrid materials possessed a good potential for the preparative enantioseparation of optically pure enantiomers,and the loading capacity of AC-6 was 4 times that of the coated type CSP.A series of organic-inorganic hybrid chiral packing materials with high cellulose derivative content were prepared by base catalysis sol-gel method.The hybrid materials have regular morphologies,uniform particle size distribution,large specific surface area and narrow pore size distribution.As well as,the organic content of hybrid materials is between 30 wt%～ 40wt%,which can be controlled.In the process of preparing hybrid materials by sol-gel method catalyzed by alkali,the amount of solvents such as alkali and water and the reaction temperature have great effects on the morphology,particle size distribution and the proportion control of organic and inorganic components of the hybrid materials.With the increase of the amount of solvent,the regularity of the hybrid material was improved and the particle size distribution was more uniform.The chiral recognition ability of hybrid materials was evaluated by HPLC.The results showed that those materials.The chiral separation results of Rac-1～Rac-5 and Rac-7 on the base-catalyzed hybrid materials were better than those on CPM-1 and commercial column Chiralpak IB.The interaction between the synthesized derivatives and different enantiomers was simulated,and the optimal conformation between the derivatives and enantiomers was obtained under the condition of the lowest energy based on the principles of molecular mechanics and molecular dynamics.To further explore the chiral recognition mechanism of cellulose derivatives,the simulation results were compared with the results of HPLC separation.The molecular simulation results showed that the elution sequence of the enantiomers predicted by the simulation was exactly the same as that of the chromatographic resolution,and the interaction energy difference calculated by the simulation was basically consistent with the variation rule of the energy difference ΔΔG calculated by the chromatographic resolution.Cellulose derivatives can form π-π stacking,T-type π-π,π-s,π-alkyl,conventional hydrogen bonds and atypical hydrogen bond with enantiomers in their chiral grooves,which have an important impact on their chiral recognition abilities.