Quantitative prediction of enantioseparation using β-cyclodextrin derivatives as chiral selectors in capillary electrophoresis

Abstract

β-Cyclodextrin derivatives as chiral selectors are becoming increasingly important for enantioseparations in capillary electrophoresis (CE). Nevertheless, there are some enormous challenges in choosing effective selectors from a variety of compounds, and up to now no systematic quantitative studies for predicting the possibility of enantiomeric separation before CE experiments have been reported. In this paper, in order to resolve previous confusions, we investigated the enantioseparations of ten chiral drugs using a method of combining experiments with theoretical calculations. MMFF, PM3, DFT and ONIOM2 methods were simultaneously utilized during the course of our computer simulations. The results indicated that a specific value of greater than or approximately equal to 6 kJ mol(-1) for the interaction energy difference (ΔΔE) between a pair of enantiomers with a selector is required in order to achieve enantiomeric separation. This discovery offers a meaningful reference to predict enantiomeric separations, so as to design and synthesize some more efficient chiral selectors.

DFT-D4 Insight into the Inclusion of Amphetamine and Methamphetamine in Cucurbit[7]uril: Energetic, Structural and Biosensing Properties

“…Indeed, S-AMP@CB [7] and S-MET@CB [7] are found to be 3.18 and 1.31 kJ/mol more stable than the complexes R-AMP@CB [7] and R-MET@CB [7]. The small difference in their complexation energies suggests the formation of a racemic mixture of AMP and MET enantiomers [72], as observed in the X-ray crystal structures of the host-guest complexes where both forms of R and S enantiomers were found. Based on the frequency calculations, we determined ∆G Complexation at temperature 298K for each complex and compared it with the experimental values.…”

Primary vs Secondary: Directionalized Guest Coordination in β-Cyclodextrin Derivatives

“…The first 11 atoms of each repeating unit are heavy atoms, while the other (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) atoms are hydrogen atoms.…”

“…As a result, in computational investigations of host-guest coordinations, there is a tendency to simplify the modelling procedure by neglecting conformational flexibility and considering only a single binding mode. [11][12][13][14][15][16][17][18] As a result, the computational inspection of host-guest binding is simplified to a singlestate calculation that can be treated via single-point calculations with normal mode approximation or restrained sampling in the neighborhood of the initial bound configuration. However, recent modelling reports with comprehensive conformational sampling suggest the pivotal role of the conformational flexibility of both components involved in host-guest coordination and a general multi-modal binding behavior in host-guest complexes, [19][20][21][22][23] which suggests that the single-state approximation, regardless of the accuracy level of the employed Hamiltonian, could introduce systematic biases of unknown magnitude.…”

Chiral Separations by Capillary Electrophoresis and related Techniques with Different Chiral Selectors: A Review

“…In addition, the plurality of CD derivatives across the spaces and substituents meets the possibility of enantiomeric separation for large-scale chiral compounds [152]. CDs act as chiral selectors to separate enantiomers and are suitable for related strategies, such as capillary derivatization, inclusion complex formation mec-hanism, chiral recognition, molecular modeling, quantitative approaches, also detection of analytes [153][154][155][156][157][158][159][160][161][162][163]. 15 different cyclodextrin derivatives were investigated as a chiral complexing reagent.…”