Design, Synthesis, and Applications of Bis-Amido HPLC Pirkle-Type Chiral Stationary Phases

Abstract

Two different types of chiral stationary phases, based on Pirkle's design, were created by attaching chiral selectors to 3-mercapto silica gel. To prepare the enantiomeric selectors, 3,5-dinitrobenzoyl and naphthyl groups were sequentially added to a chiral 1,2-diaminocyclohexane core. The chiral selectors demonstrated enantioselectivity towards ibuprofen enantiomers in solution, as confirmed by ¹H NMR spectroscopy, and in initial HPLC testing, the enantiomeric selectors showed enantioselectivity for selected racemic solutes (viz., α = 1.27 for1,1′-bi-(2-naphthol)). Molecular docking studies revealed that the chiral selectors had a bent structure and a cleft-like cavity where the analyte could be held during complexation while establishing H-bonding and π–π stacking interactions.