Theoretical Study On Chiral Recognition Mechanism Of Ethyl-3-Hydroxybutyrate And Ethyl-3-(2,2,2-Trifluoroacetoxy) Butyrate With PMBCD

In this thesis, the studies of cyclodextrins host-guest chiral recognition mechanism were carried out by molecular simulation method, including the semiempirical PM3 method, ONIOM method and NBO analysis. The nature of chiral recognition and host-guest interaction force were stated from the molecular level.Chiral recognization mechanism of permethlated-β-cyclodextrin (PMBCD) with enantiomers of ethyl-3-hydroxybutyrate ((R/S)-EHB) was simulated by the semiempirical PM3 method. Then took the hybrid ONIOM method which models the PMBCD at the PM3 level and the guest molecule using B3LYP/6-31g(d) for precise calculation. The modeling results showed the stabilization complexation structures which formed with (R/S)-EHB enantiomers and PMBCD were different. (S)-EHB was located on the cavity wide mouth end of PMBCD to form an associated molecule, but the esterfunction of (R)-EHB inserted into the PMBCD cavity to form an inclusion molecule. So the hydrophobic forces between (R)-EHB and PMBCD are bigger than that of (S)-EHB and PMBCD. The binding energy of (S)-EHB/PMBCD was less than that of (R)-EHB/PMBCD. And in (R/S)-EHB/PMBCD inclusion complex, the chiral carbon of (R/S)-EHB are both close to C2 and C3 in glucose unit, thus the chiral selector capacity is mainly due to the chiral environment provided by C2 and C3 in the glucose unit. Morever, the Natural Bond Orbital (NBO) results show the hydrophobic forces and the charge transfer interactions are the main forces in the chiral recognition mechanism of (R/S)-EHB enantiomers on PMBCD.The host-guest complexation of permethlated-β-cyclodextrin (PMBCD) with enantiomers of ethyl 3-(2,2,2-trifluoroacetoxy) butyrate ((R/S)-ETB) was simulated by semiempirical PM3 method. The modeling results showed both (S)-ETB and (R)-ETB inserted into the PMBCD cavity to form inclusion molecule, but the molecular geometries of the most stable complexes were quite different. The binding energy of (R)-ETB/PMBCD was less than that of (S)-ETB/PMBCD. And the chiral carbon of (R/S)-ETB are both close to C2 and C3 in glucose unit. The Natural Bond Orbital (NBO) results show that the H-bond and hyperconjugation interactions of (S)-ETB/PMBCD are bigger than (S)-ETB/PMBCD. So the chiral recognization mechanism were closely related to the chiral environment provided to C2 and C3 in glucose unit and H-bond, hyperconjugation interactions of (R/S)-ETB and PMBCD.