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

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., alpha = 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 pi-pi stacking interactions.The protocol for developing new CSPs using synthetic selectors involves the following steps: (i) Synthesize chiral molecules capable of multiple interactions, (ii) evaluate enantiorecognition, (iii) anchor on silica, (iv) evaluate thermodynamics, and (v) assess stability of selector-selectand adducts via molecular docking.image