Preparation Of Silica-based Cellulose Hybrid Particles And Chiral Polymers Of Intrinsical Porosity For Chiral Separation

Recognition, design, separation and purification of chiral molecules are crucial to the development of modern biology and pharmaceutical engineering. High performance liquid chromatography is one of the most important methods for chiral separation. However, current commercial chiral columns are still facing problems such as low loading capacity and lack of mechanical strength, which limits its application on large-scale preparative chiral separation. On the other hand, membrane-mediated enantiomer separation offers an alternative technology. Low-energy consumption, high processing capacity and continuous operation suggest membrane processes can satisfy many of the criteria for large-scale enantiomer enrichment. But inverse proportionality of permeability and permeation selectivity for reported chiral membranes limits their industrial applications.This thesis focuses on preparation of silica-based cellulose hybrid stationary phase and chiral polymers of intrinsic porosity for chiral separation.A hybrid cellulose 3,5-dimethylphenylcarbamate chiral stationary phase (organic/inorganic: 70/30, w/w) was prepared via a sol-gel method. In addition, the as-synthesized hybrid chiral silica spheres were treated with an end-capping process to mask the residual silica hydroxyl groups, allows it to separate basic racemates and more than 70% of standard racemantes can be separated. Separation of commercialized anti-hypertension β-blocker drugs reached far better than baseline separation on the end-capped CSP, which is close to commercial chiral column Chiralcel OD, among them, pindolol reaches to selectivity of 5.5.Preparation of these hybrid particles with high surface area and controlled organic/inorganic ratio is challenging. We have found that by controlling the pH of the sol-gel step and regulating the weight ratio of the inorganic precursor over CDMPC, unique functional hybrid particles could be prepared with optimum surface area (500 m2/g), novel interfacial features and excellent mechanical strength. These new hybrid particles exhibit excellent solvent durability which is crucial for preparative chromatography. Separation of trifluoroanthrylethanol and pindolol has reached baseline separation. HPLC analysis of columns packed with this material confirmed solvent tolerance such as chloroform, giving potential applications for large scale chromatographic separations.On the membrane issue, we report the first synthesis of a chiral polymer of intrinsic microporosity ((+)-PIM). (±)-5,5’,6,6’-Tetrahydroxy-3,3,3’,3’-tetramethyl spirobisindane (TTSBI) was resolved by diastereomeric complexation. The enantiopure spirobisindane was used to synthesize a chiral ladder polymer, (+)-PIM-CN. (+)-PIM-COOH was synthesized by acid hydrolysis of (+)-PIM-CN. Following characterization, both (+)-PIM-CN and (+)-PIM-COOH were evaluated for their ability to selectively transport a variety of racemates including mandelic acid (Man) (31 % ee), Fmoc-phenylalanine (Fmoc-phe) (75 % ee), 1,1’-Bi-2-naphthol (Binol) (53 % ee) and TTSBI (87 % ee) with high permeation rates. A selective diffusion transport mechanism was consistent with the results from (+)-PIMs material. Their high permeability, processability and ease of chemical modification offer considerable potential for liquid phase membrane separations and as media for related separation applications like HPLC material and chiral MOFs ligand.