No abstract

Enantioselectivity of the propranolol on β-cyclodextrin was simulated by molecular modeling. Monte Carlo (MC) docking and molecular dynamics (MD) simulations were applied to investigate the molecular mechanism of enantioselective difference of both enantiomeric complexes. An energetic analysis of MC docking simulations coupled to the MD simulations successfully explains the experimental elution order of propranolol enantiomers. Molecular dynamics simulations indicate that average energy difference between the enantiomeric complexes, frequently used as a measure of chiral recognition, depends on the length of the simulation time. We found that, only in case of much longer MD simulations, noticeable chiral separation was observed.

Molecular modeling was performed to comprehend the chiral recognition of α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) enantiomers by cyclomaltoheptaose (β-cyclodextrin, β-CD) and 6-amino-6-deoxycyclomaltoheptaose (am-β-CD). Monte Carlo (MC) docking coupled to constant temperature molecular dynamics (MD) simulations was applied to the investigation for the α-methoxy-α-trifluoromethylphenylacetic acid complexation with two different CDs in terms of the relative distribution of the interaction energies. The calculated results are finely correlated with the experimental observations in chiral recognition thermodynamics. Am-β-CD as a host showed the superior enantio-discrimination ability to the native β-CD where the amino group of am-β-CD was critically involved in enhancing the ability of chiral discrimination via the Coulombic interaction with MTPA.