Enantioselective binding of α-pinene and of some cyclohexanetriol derivatives by cyclodextrin hosts: A molecular modeling study

Abstract

We have used molecular modeling to investigate the enantioselective separation of the monoterpene α‐pinene on permethylated β‐cyclodextrin and on α‐cyclodextrin and the enantioselective separation of three cyclohexanetriol derivatives on permethylated β‐cyclodextrin. Using the Consistent Valence Force Field (CVFF) from Insight/Discover, we have carried out systematic rigid‐body docking grid searches on each of the optical antipodes of the organic guest molecules interacting with the cyclodextrins, followed by minimizations of the low‐energy docked structures. A statistical mechanical analysis of the minimized energies yields data that agree in four out of five cases with the experimental elution order of enantiomers. The computed energies of the rigid‐body docking before minimizations do not agree with the experimental results, suggesting that a conformational induced fit of the cyclodextrins upon binding of the organic guests may be involved in the mechanism of the chiral recognition. © 1996 by John Wiley & Sons, Inc.

Explanation of Where and How Enantioselective Binding Takes Place on Permethylated β-Cyclodextrin, a Chiral Stationary Phase Used in Gas Chromatography

“…This issue was addressed in an earlier paper where we found the induced fit changes for type I CSPs to be small and inconsequential with regards to the computed free energy differences we felt less confident that such a sampling protocol would work because it has been speculated that induced fit structural changes are especially important when cyclodextrins bind guest molecules and, consequently, that an alternative methodology accounting for such changes, like molecular dynamics, would be better suited for this task (see below) …”

“…A large number of molecular dynamics simulations of cyclodextrin host−guest complexes can be found in the literature, but most of them do not consider the topic of enantioselective binding . However, several MD simulations did focus on prediction of analyte elution order, and these are noted. ,, The computational approach taken in those studies is to dock the guest molecule inside the host cavity, energy minimize the complex, and carry out standard warmup, equilibration, and production runs to derive an averaged energy for R and an averaged energy for S analytes. Starting the trajectory from the interior of the CD is predicated on the understanding that most guests bind to the interior of these macrocycles in solution.…”

Dimerization and α-Cyclodextrin Inclusion of Propantheline Bromide as Studied by NMR and Molecular Modeling

“…Their aggregates are formed by the stacking of aromatic rings in most cases. − The solution structures of CyD inclusion complexes are estimated by NMR spectroscopy, circular dichroism, and molecular modeling. However, the estimated structures are rather rough in most cases. − Johnson and Bovey proposed the theory which estimates the magnitude of the shielding effect of the benzene molecule on the chemical shift of a proton . Yamamoto et al applied this theory to determine the solution structures of the equimolar complexes of 4-nitrophenol with CyDs …”

Molecular Modeling of the Enantioselectivity in Lipase-Catalyzed Transesterification Reactions

“…With systems where the lock and key concept (Fischer, 1894) works, this should be a successful way to calculate the difference in free energy. However, this approach is not appropriate when the enzyme must rearrange its geometry in order to accommodate the substrate in accordance with the induced fit concept (Haldane, 1930;Black et al, 1996). Releasing all geometrical constraints means more costly simulations in addition to larger energy fluctuations.…”