Preparation of two new anionic β-cyclodextrin-based hybrid monolithic chiral stationary phases for CEC enantioseparations of drugs and molecular modeling of enantiomer-chiral selector interactions.

Two anionic β-cyclodextrin-based nanohybrid monolithic columns were synthesized and applied in CEC enantioseparation with UV detection. The first monolithic column was fabricated via a "one-pot" approach using glycidyl methacrylate-functionalized sulfated β-cyclodextrin (GMA-S-β-CD), sodium 3-mercaptopropanesulfonate, and alkoxysilanes. The second column was prepared similarly using glutamate-modified β-cyclodextrin (GMA-Glu-β-CD) as the chiral stationary phase. Compared to the Glu-β-CD monolith, the S-β-CD column exhibited significantly higher separation efficiency, achieving baseline separation for 19 out of 27 chiral drugs-including antibiotics, antihistamines, azoles, and other therapeutic agents-whereas the Glu-β-CD monolith resolved only 14. Repeatability was excellent, with relative standard deviations (RSDs) below 4.84% for run-to-run, day-to-day, and column-to-column analyses. Furthermore, quantum mechanics-molecular mechanics (QM-MM) simulations were employed to elucidate the differences in interaction strengths between enantiomers and cyclodextrins within the inclusion complexes.