Enantioseparation and chiral recognition of α-cyclohexylmandelic acid and methyl α-cyclohexylmandelate on hydroxypropyl-β-cyclodextrin as chiral selector: HPLC and molecular modeling.
Enantioseparations of (R/S)-α-cyclohexylmandelic acid [(R/S)-CHMA] and methyl (R/S)-α-cyclohexylmandelate [(R/S)-MCHMA] were performed on an achiral column (ODS) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobile phase additive. The influences of chromatographic conditions on the retention behavior of (R/S)-CHMA and (R/S)-MCHMA were studied in detail. Meanwhile, the thermodynamics parameters of enantioseparations for (R/S)-CHMA and (R/S)-MCHMA were determined to discuss driven power in the enantioseparation process. The inclusion complexation of HP-β-CD with each enantiomer for (R/S)-CHMA and (R/S)-MCHMA was simulated by molecular docking to understand the chiral recognition mechanism of (R/S)-CHMA and (R/S)-MCHMA on HP-β-CD. The results showed that the chiral recognition ability of enantiometers of (R/S)-CHMA and (R/S)-MCHMA on HP-β-CD is better than α-CD, β-CD, γ-CD and DM-β-CD. Under the selected chromatographic conditions, baseline separations of enantiomers of (R/S)-CHMA and (R/S)-MCHMA were achieved. It is proved that the stoichiometry for (R/S)-CHMA-HP-β-CD and (R/S)-MCHMA-HP-β-CD complexes is 1:1. However, the results of thermodynamics parameters analysis and molecular modeling show that the enantioseparations of CHMA and MCHMA on HP-β-CD are enthalpy-driven processes and the primary driving forces responsible for chiral recognition are hydrophobic forces, dipole-dipole interaction, charge-transfer and hydrophobic interaction.
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, China. shijh@zjut.edu.cn
Jie-hua
JH
Shi
Yan-hui
YH
Su
Wei
W
Jiang
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008333:Mandelic Acids / Q000737:chemistry* / Q000302:isolation & purification*; D000432:Methanol / Q000737:chemistry; D062105:Molecular Docking Simulation / Q000379:methods*; D013237:Stereoisomerism; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D008333:Mandelic Acids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000432:Methanol