Theoretical study on chiral recognition mechanism of ethyl-3-hydroxybutyrate with permethylated β-cyclodextrin

The inclusion interactions between permethylated β-cyclodextrin (PMβCD) and enantiomers of ethyl-3-hydroxybutyrate ((R/S)-EHB) were simulated using the semi-empirical PM3 and ONIOM (B3LYP/6-31g(d):PM3) methods. The chiral recognition mechanism of (R/S)-EHB enantiomers on PMβCD was investigated. The modeling results showed that the most stable geometries of two (R/S)-EHB/PMβCD complexes were obviously different. The ethoxy group of (S)-EHB is nearly prostrated at the wider rim of PMβCD cavity, as the ethoxy group of (R)-EHB inserted into the hydrophobic cavity of PMβCD. The results showed that the binding energy (BE) and total stabilization energy (EONIOM) of (R)-EHB/PMβCD complex both are lower than that of (S)-EHB/PMβCD complex and the total charge transfer of (R)-EHB/PMβCD complex is greater than that of (S)-EHB/PMβCD, indicating that the (R)-EHB/PMβCD complex is more stable than the (S)-EHB/PMβCD complex. Furthermore, it can be deduced from the results obtained by NBO analysis that the main driving forces in the chiral recognitions of (R/S)-EHB enantiomers on PMβCD are weak hydrogen bonding interaction, dipole–dipole interaction, charge-transfer function and hydrophobic interaction, which leads to form different geometric structures of (R/S)-EHB/PMβCD complexes. However, in (R/S)-EHB/PMβCD complexes, the chiral carbon of (R/S)-EHB are both close to C2 and C3 in glucose units, so the chiral selector capacity is mainly due to the chiral environment provided by C2 and C3 in glucose units and the tightness of combining between (R/S)-EHB and PMβCD.