Study On Chiral Recognition Mechanism Of Naproxen On Polysaccharide-based Chiral Stationary Phases

Chromatographic enantioseparation on chiral stationary phases (CSPs) represents one ofthe most direct and facile approaches for the determination of enantiomeric purity and thepreparation of pure enantiomeric drugs. So, the study of chiral recognition mechanism and thesynthesis of CSPs are very important. This article mainly discussed the enantioseparations ofnaproxen on two polysaccharide-based CSPs, including Chiralpak IA and Chiralcel OD-H.Following aspects were represented in this study.1. In the introduction section, the importance of chiral recognition and the progress ofchiral recognition study have been reviewed. The importance and methods of chiral separationare briefly introduced. the reported six kinds of CSPs, including Pirkle type CSPs, proteinCSPs, macrocyclic CSPs, ligand exchange CSPs, molecular imprinting CSPs and polymerCSPs are briefly reviewed. The thermodynamic method for the study of chiral recognitionmechanism is also reviewed. The reversal of elution order between the two enantiomers isexplained.2. Enantioseparation of naproxen was performed on an immobilizedpolysaccharide-based chiral stationary phase (CSP), Chiralpak IA, in the normal-phase mode.The effects of polar alcohol modifier in the mobile phase and column temperature (20-50℃)on the retention, enantioseparation and elution order were investigated in detail. Two unusualphenomena were observed. One was solvent-induced reversal of elution order for the twoenantiomers. Not only the type but also the content of polar alcohol modifer could induce thereversal. Another uncommon phenomenon was peak deformation under somechromatographic conditions. The system peak of acetic acid likely caused the peakdeformation in the chromatographic system. Solvent-induced reversal of elution order for thenaproxen was obtained, temperature-induced inversion of elution order for naproxen was notobserved directly. In a previous study,1,1’-bi-2-naphthol (BINOL) was enantiosepated onChirapak IA in the normal-phase mode. A domain in which enantioseparation can not beobtained can be named as “temperature-induced blind zone” or “solvent-induced blind zone” of chiral recognition. In this zone, chiral recognition becomes invalid. Farther away from theblind zone, better chiral recognition should be obtained. It is important to anticipate whensuch temperature-induced and solvent-induced inversions of elution order would occur.Another meaningful aspect is, how to shift one enantioseparation into suitable domain whichis far away from the “blind zone”. The reason for the reversals was elucidated based on Van′tHoff equation and the stoichiometric displacement theory for retention. Some misleadingdiscussions about chiral recognition mechanism were also pointed out.3. Enantiosepation of naproxen on a coated polysaccharide-based chiral stationary phase,Chiralcel OD-H, was also studied under normal-phase mode. The effects of type and contentof polar alcohol modifier in the mobile phase and column temperature (20-50℃) on theretention, enantioseparation and elution order were investigated in detail.Temperature-induced and solvent-induced inversions of elution order for naproxen were notobserved directly. Enantiosepation of BINOL diacetate and dicinnamate on Chiralpak IA wasalso studied.