A chromatographic and computational study on the driving force operating in the exceptionally large enantioseparation of N-thiocarbamoyl-3-(4'-biphenyl)-5-phenyl-4,5-dihydro-(1H) pyrazole on a 4-methylbenzoate cellulose-based chiral stationary phase

Abstract

This paper describes the results obtained in the HPLC enantioseparation of N-thiocarbamoyl-3-(4'-biphenyl)-5-phenyl-4,5-dihydro-(1H) pyrazole on a cellulose tris(4-methylbenzoate) chiral stationary phase (OJ-3 CSP) using normal-phase and polar organic conditions. The enantioseparation factor (α=207) observed using the mixture n-hexane-2-propanol 70:30 as a mobile phase is among the highest values ever reported in enantioselective HPLC. The enantioseparation process was investigated by means of molecular modelling techniques. Chromatographic and theoretical investigations addressed the extreme affinity of the most CSP retained (S)-enantiomer to the intermolecular H bond network between the ligand thioamide group and the stationary phase O atoms.

Keywords: Chiral stationary phase; Chiralcel OJ-3; Enantiomer separation; High enantioselectivity; Molecular dynamics; Temperature effects.