Short Bridging and Partial Derivatization Synergistically Modified Β-Cyclodextrin Bonded Chiral Stationary Phases for Improved Enantioseparation

Abstract

β-Cyclodextrin (β-CD) and its derivatives have been widely employed in the field of chiral separation, but they are still faced the limitation of low enantioselectivity and complex processes. Derivatization with functional molecules or preparation as bridging dimers are the two main modifications for β-CD to obtain chiral recognition compounds. Herein, a partially derived bridged β-CD (CPI-EBCD) bonded chiral stationary phase was prepared to improve enantioseparation. The chiral recognition moiety was synthesized by a bridged β-cyclodextrin dimer using a short-chain bridging agent (ethylenediamine) and then modifying the bridged cyclodextrin with a 4-chlorophenylisocyanate (CPI) containing a benzene ring and polar group. Compared with natural β-CD, dual-chambered CPI-EBCDs have better encapsulation synergies and more recognition sites with the guest molecule, while the short flexible bridging groups make the double cavities closer and more easily recognizable as linear molecules. The introduction of derived groups CPI provided more recognition sites and more types of interactions, including π-π interaction force, hydrogen bonding effect, and dipole-dipole interaction, thus improving the enantiomer-specific chirality recognition effect. The chiral stationary phase CPI-EBCDP was obtained by connecting CPI-EDCB with mesoporous silica microspheres by simple photochemical reaction using a green non-toxic diazo resin as coupling agent, simplifying preparation process. In the reversed phase mode of liquid chromatography, CPI-EBCDP has excellent chiral recognition ability, and 12 chiral compounds are successfully isolated by optimizing mobile phase conditions, with good reproducibility and stability. The successful preparation of this new chiral stationary phase provides an important reference for the subsequent development of cyclodextrin-like chiral stationary phases.

Keywords: Bridged β-cyclodextrin, 4-chlorophenylisocyanate, Diazo resin, High performance liquid chromatography, Chiral separation