Molecular Simulation of the Separation of Some Amino Acid Enantiomers by β-Cyclodextrin in Gas-Phase

Abstract

The complexes formed by β-cyclodextrin and some amino acids (alanine, valine, leucine, and isoleucine) in vacuo are studied by molecular mechanics and dynamics simulations. These methods have been improved with respect to our previous studies with amino acids, regarding the determination of molecular structures or initial enantiomer dispositions in the molecular dynamics trajectories. The greatest contribution to the interaction energy is from the van der Waals term, although the discrimination between enantiomers is due mainly to the electrostatic contribution. The lowest energy structures of the complexes obtained from molecular mechanics are inclusion complexes in which the carboxylic end of amino acids is pointing toward the narrow (D-) or wide rim (L-) of β-cyclodextrin. The position probability density provided by molecular dynamics also confirms inclusion complex formation, because the guests spend most time inside the cavity of β-cyclodextrin along its axis, with the carboxylic end pointing toward the narrow rim. The L-amino acids are the first eluted enantiomers in all cases and chiral discrimination increases with the size of guests, except leucine, which has the lowest capacity to discriminate. During the simulation, Ala and Val remain in weakly enantioselective regions, while Leu and Ile stay in zones with great chiral selectivity.

Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-β-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR

“…In addition to the problems with equilibrating, it is worth asking if the molecular mechanics-based MD computations are generally accurate enough to notice the enantioselectivity of the complexation and if the observed energy differences are not just random fluctuations. Many examples of successful molecular modeling in cases of enantiodiscrimination or enantioseparation by cyclodextrines can be found in the literature [19,43,44]. The calculated binding energies are certainly not quantitative, as the accuracy of the molecular mechanics calculations is rather limited [42].…”

Insights into Structural Features and Ternary Phase Diagrams of Prednisolone/β-Cyclodextrin Inclusion Complex

“…In recent years, molecular simulation techniques have been frequently used to study the formation mechanism of ICs. , Molecular dynamics (MD) allows for the simulation of the IC formation process by visualizing the trajectory of the host and guest molecules and their mode of action at the molecular level. , Moreover, information can be gathered about the exact structure, energy, and other characteristics of the complexes using quantum chemical techniques . Alvira et al investigated the formation of ICs of β-CDs with amino acids under vacuum conditions and the chiral separation of these enantiomers by molecular mechanics and molecular dynamics. Imamura et al performed quantum chemical calculations and MD simulations to analyze the molecular interaction mechanism of cyclic glucan with the guest molecule.…”

“…28,29 Moreover, information can be gathered about the exact structure, energy, and other characteristics of the complexes using quantum chemical techniques. 30 Alvira et al 31 investigated the formation of ICs of β-CDs with amino acids under vacuum conditions and the chiral separation of these enantiomers by molecular mechanics and molecular dynamics. Imamura et al 32 performed quantum chemical calculations and MD simulations to analyze the molecular interaction mechanism of cyclic glucan with the guest molecule.…”