Enantioseparation of mandelic acid and substituted derivatives by high‐performance liquid chromatography with hydroxypropyl‐β‐cyclodextrin as chiral mobile additive and evaluation of inclusion complexes by molecular dynamics

Abstract

The enantioseparation and resolution mechanism of mandelic acid (MA), 4-methoxymandelic acid (MMA), and 4-propoxymandelic acid (PMA) were investigated by reversed-phase high-performance liquid chromatography (HPLC) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobilephase additive and molecular dynamics simulation. The suitable chromatographic conditions for the enantioseparation of MA, MMA, and PMA were obtained. Under the selected chromatographic conditions, these enantiomers could achieve baseline separation. The results of thermodynamic parameter analysis revealed that the main driven forces for the enantioseparation of MA, MMA, and PMA could be van der Waals forces and hydrogen-bonding interactions and the chromatographic retention of these chiral compounds was an enthalpy-driven process. The results of the molecular simulation revealed that their chiral resolution mechanism on HP-β-CD was responsible for the formation of inclusion complexes of enantiomers with HP-β-CD with different conformations and binding energies. And the binding energy of HP-β-CD with (S)-isomer was larger than that with (R)-isomer, which is consistent with the experimental results of the first elution of (S)-isomer. Additionally, it is also confirmed that the interaction energies included the van der Waals energy (ΔE vdw ), electrostatic energy (ΔE elec ), polar solvation energy, and SASA energy (ΔE sasa ), and the separation factor (α) was closely connected with the disparity in the binding energies of optical isomers and HP-β-CD complexes. Meanwhile, from molecular dynamics simulation, it can be found that the Δ (ΔE binding ), (Δ(ΔE binding ) = ΔE binding,R À ΔE binding,S ) value was in order of MA-HP-β-CD complex > MMA-HP-β-CD complex > PMA-HP-β-CD complex, which was consistent with the order of Δ(ΔG) values obtained from van't Hoff plot. This indicated that the molecular dynamics simulation has predictive function for chiral resolution.

Enantioseparation of basic drugs by reverse phase high‐performance liquid chromatography system using carboxymethyl‐β‐cyclodextrin as chiral mobile phase additive

“…The interaction between the enantiomer and CM‐β‐CD, as well as the interaction between the inclusion and the stationary phase adsorption site, could be investigated further via thermodynamic analysis in order to better understand the enantiomer separation mechanism in chromatographic separation. The relationship between the capacity factor( k ′) or separation factor (α) and the column temperature (T) during chromatographic chiral separation process can be described by the van't Hoff and Gibbs–Holmholtz equations as follows 17 : where k ′ is the capacity factor of enantiomer and α is the separation factor of two racemic isomers. ΔG, ΔH, and ΔS represent the Gibbs free energy change, the enthalpy change, and the entropy change, respectively.…”

“…The subscript 1 means the data belong to the enantiomer eluting first, and the subscript 2 means the data belong to the enantiomer eluting second investigated further via thermodynamic analysis in order to better understand the enantiomer separation mechanism in chromatographic separation. The relationship between the capacity factor(k 0 ) or separation factor (α) and the column temperature (T) during chromatographic chiral separation process can be described by the van't Hoff and Gibbs-Holmholtz equations as follows 17 :…”

“…11,12 On the other hand, the method of utilizing the CMPA has been widely used in exploratory research as a versatile and flexible method to demonstrate greater potential in chiral separation. 13,14 So far, a wide range of chiral selectors, including cyclodextrins (CDs), [14][15][16][17][18] chiral ion-pair inclusions, 19,20 and chiral ligand-exchange inclusions, [21][22][23] have been explored in CMPA techniques.…”

Pb2+ Responsive Cu-In-Zn-S Quantum Dots With Low Cytotoxicity

“…Elucidating the thermodynamic parameters might help provide clues on the involvement of these forces in the conjugation process. According to the view of Ross ( Jiang et al, 2019 ; Li et al, 2020 ; Shi et al, 2021 ), when Δ H θ < 0 and Δ S θ < 0 were associated with hydrogen bonding or van der Waals forces, the negative values obtained for both Δ H θ (−4.428 × 10 4 J·mol −1 ) and Δ S θ (−1.144 × 10 2 J·mol −1 K −1 ) in this study suggested the involvement of hydrogen bonding or van der Waals forces in the formation of Pb 2+ and CIZS QDs. The negative enthalpy change is due to the broken Pb 2+ -H 2 O bond, which is favorable for the formation of the Pb 2+ -CIZS QD complex, while the negative entropy contributes to the formation of the complex that decreases the chaos of the interaction system.…”

A covalent organic framework for chiral capillary electrochromatography using a cyclodextrin mobile phase additive

“…31 For example, fipronil have two aromatic rings, which may fit better in the CD cavity; the presence of hydroxyl or carbonyl groups in histidine can enhance the hydrogen bond interaction between hydroxyl groups of CD and histidine. 32 The results showed that all the analytes could be rapidly separated from the baseline under the optimized conditions of Method 2 with a resolution > 1.5 and a separation factor (α) > 1.05 (Table 2). It may be possible that a positive mutual synergy existed between HP-β-CD and COF TpBD for enantiomers of each analytes.…”