Enantioseparation and modeling study of selected chiral pharmaceuticals on a commercialized phenylcarbamate-β-cyclodextrin column using polar organic mode

Abstract

The chiral separation capability of Chiral-CD-Ph column, containing phenylcarbamate-β-cyclodextrin as the chiral selector in polar organic mode was investigated. A total of 25 compounds with different structures and acid-base properties were tested, and 20 of them were separated using acetonitrile or methanol as eluent. The effects of various chromatographic parameters, such as the type and proportion of organic modifier, flow rate, and column temperature were analyzed in detail in relation to chromatographic performance. A U-shape retention curve was observed when a mixture of acetonitrile and methanol was used as the eluent, indicating different types of interactions in different solvent mixtures. Van 't Hoff analysis was used for calculation of thermodynamic parameters which revealed that the enantioseparation is mainly enthalpy controlled; however, entropic control was also observed. The enantiomer recognition ability at the atomic level was also investigated through a molecular modeling study, which revealed surface binding in polar organic mode instead of inclusion complexation. Our work proves that the phenylcarbamate-β-cyclodextrin chiral selector can be effectively used in polar organic mode for the chiral separation of compounds with diverse structures. Furthermore, it is also important to note that it was demonstrated that surface binding is responsible for the formation of supramolecular complexes in certain cyclodextrin derivatives.