Experimental and Theoretical Studies on the Enantioseparation and Chiral Recognition of Mandelate and Cyclohexylmandelate on Permethylated β-Cyclodextrin Chiral Stationary Phase

Abstract

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.

How to simulate affinities for host–guest systems lacking binding mode information: application to the liquid chromatographic separation of hexabromocyclododecane stereoisomers

“…Taking the natural logarithm of k is justified by thermodynamic studies of the chromatographic retention behavior revealing a linear correlation between ln(k) and thermodynamic quantities such as the inversed temperature, the Fig. 6 Low energy conformations of (−)-γ-HBCD within the β-pmCD (represented by its solvent-excluded surface) cavity with a mass center distance of 3 Å on the left-hand and of (+)-β-HBCD with a distance of 5.8 Å on the right-hand fetched from the equilibrium region of an MD simulation with explicit water enthalpy and free energy [56,57]. In order to figure out the correlation model's robustness, these coefficients were averaged over multiple time ranges starting at succeeding time frames with 20 ps offsets, but all ending at 360 ps.…”

Characterization of Calixarene/Ionic Liquid Mixture as Gas Chromatographic Stationary Phase through Thermodynamic Parameters and LSER

“…In the process of chromatographic separation, the relationship between the retention factor (k) and column temperature (T) can be described by the following equations [25]:…”

Study on the separation of ofloxacin enantiomers by hydroxyl-propyl-β-cyclodextrin as a chiral selector in capillary electrophoresis: a computational approach

“…The methods employed include molecular mechanics, molecular dynamics, semiempirical methods and density functional theory calculations [4,[18][19][20][21][22][23][24][25][26]. Semiempirical methods are attracting lots of attention in the simulation of CD-inclusion compounds due to their reasonable accuracy and less computational demands.…”