Enantioseparations of methyl mandelate (MMA) and methyl a-cyclohexylmandelate (MCHMA) on permethylated b-cyclodextrin (PM-b-CD) chiral stationary phase were explored in detail using high-performance liquid chromatography. The influence of the concentration of organic modifiers, along with the column temperature, was studied. In addition, the thermodynamics parameters of the enantioseparations were determined to discuss driven power in the process of enantioseparations. In addition, host-guest complexation of PM-b-CD with MMA enantiomers was simulated by quantum mechanics PM3 method for understanding the chiral recognition mechanism. The experimental results showed that the retention factor (k), separation factor (a), and resolution factor (Rs) for MMA and MCHMA resolved on the PM-b-CD column all generally decreased with the increase of methanol content, which indicated that the main chiral recognition mechanism is that the hydrophobic portions of MMA and MCHMA are included in the hydrophobic cavity of PM-b-CD to form inclusion complexes. In addition, there is an excellent linear relationship between the logarithms of retention factors (k) of MMA and MCHMA enantiomers and 1/T. It was demonstrated that the enantioseparations of MMA and MCHMA on PM-b-CD chiral column were enthalpy-driven processes. The modeling results can correctly predict the retention order and provide an atomistic account of how chiral discrimination takes place. It is found that the most stable structure of (R)-MMA/PM-b-CD complex is different with that of (S)-MMA/PM-b-CD complex. The main driving forces responsible for chiral recognition are hydrophobic forces and weak hydrogen bondings.

Host-guest interactions of permethylated β-cyclodextrin (PM-β-CD) with methyl mandelate enantiomers ((R/S)-MMA) were simulated using semiempirical PM3 and ONIOM (B3LYP/6-31G(d):PM3) method. The chiral recognition mechanism of (R/S)-MMA enantiomers on PM-β-CD was investigated. The binding energies for all orientations considered in this research are reported. The most stable geometry structures of the two complexes are different. The benzene ring of (R)-MMA locates horizontally approximately on the wider edge of the PM-β-CD cavity, but the aromatic ring of (S)-MMA is deeply included into the hydrophobic cavity. Furthermore, the results of NBO analysis show that the main driving forces in the inclusion process of PM-β-CD with (R/S)-MMA are hydrogen bonding interaction, dipole-dipole interaction, charge-transfer and hydrophobic interaction. The stabilization energy of the (R)-MMA/PM-β-CD complex is lower than that of the (S)-MMA/PM-β-CD complex. Moreover, the chiral carbon in MMA of (R/S)-MMA/PM-β-CD complexes are close to the C2 and C3 in the glucose unit. The chiral recognition mechanism is thus closely related to the chiral environment provided by C2 and C3 in the glucose unit and the degree of (R/S)-MMA and PM-β-CD inclusion.

No abstract