Molecular Simulation of the Separation of Isoleucine Enantiomers by β-Cyclodextrin

Molecular mechanics and dynamics simulations were carried out to study the capacity of isoleucine enantiomers to form inclusion complexes with β⁻cyclodextrin, and to be discriminated by this chiral compound, in vacuo and with different solvents. Solvents were characterized not only by the value of dielectric constant ε in the Coulombic interaction energy, but also by the neutral and zwitterion configurations of isoleucine. Whereas the discrimination between the enantiomers for ε ≤ 2 is due to the electrostatic contribution, these differences are mainly due to the Lennard-Jones potential for ε > 2. The most enantioselective regions are located near the cavity walls, independently of the solvent. D-Ile is more stable than L-Ile in broader regions in vacuo, but L-Ile presents more stable locations with water. Isoleucine can form inclusion complexes with β⁻cyclodextrin in vacuo and with different solvents. Two probable configurations are deduced from the molecular dynamics simulation, in which the guest is always inside the cavity and with the carboxylic end of the amino acid oriented towards either rim of β⁻CD. In the simulation, the enantiomers preferentially occupy regions with greater chiral discrimination. The first eluted enantiomer in vacuo and with different solvents is L-Ile, independently of the solvent polarity.