Molecular docking study for the prediction of enantiodifferentiation of chiral styrene oxides by octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-γ-cyclodextrin

A molecular docking study, using molecular mechanics calculations with AutoDock and semi-empirical PM3 calculations, was used to help predict the enantiodiscrimination of mono-substituted styrene oxides by octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-γ-cyclodextrin (DIACTGCD), through the differences in the interaction energies and inclusion geometries. The small differences in the binding free energy values (ΔΔG) obtained from AutoDock do not show any significant enantiodifferentiation, whereas structure re-optimization with the PM3 algorithm results in larger binding energy differences (ΔΔE). All DIACTGCD–styrene oxide inclusion complexes have binding energies in the range of −13.62 to −3.83 kcal mol−1, indicating that the host–guest interactions involved are hydrophobic and van der Waals forces between the CO acetyl group, the O2/O3/O4 atoms of DIACTGCD and the substituents/epoxide group of styrene oxides. The effect of the same substituent position on the inclusion geometry is similar for all styrene oxides entirely embedded at or near the central DIACTGCD cavity. The degrees of enantiodiscrimination are: o > m > p for Cl-, CH3- and CF3-enantiomers and o > p > m for Br-, F- and NO2-enantiomers. The molecular docking results suggest that the complexation between styrene oxides and DIACTGCD depends on the type and position of the substituents on the aromatic ring. The high discriminatory ability exhibited by DIACTGCD against enantiomeric styrene oxides could potentially serve as a chiral selector, for example in chromatographic separation.