Chiral discrimination of ibuprofen isomers in β-cyclodextrin inclusion complexes: experimental (NMR) and theoretical (MD, MM/GBSA) studies

In this paper, we analyze the energetic and conformational preferences involved in the chiral discrimination of ibuprofen (Ibu) isomers by beta-cyclodextrin (β-CD) when forming inclusion complexes in water. This study was performed by means of atomistic molecular mechanics simulations upon four different penetration modes of the guest, and a structural 2D NMR experiment. The trajectories of these simulations were treated with the MM/GBSA method in order to obtain the relative weights of the different free energy components. The resulting values of the free energy of binding and other geometrical features indicate that this chiral selectivity is influenced by a preferred penetration mode involving the S-(+)-Ibu isomer. The calculated ΔΔG of binding is in good agreement with published experiments. © 2006 Elsevier Ltd. All rights reserved.