HIGH-FIELD NMR TECHNIQUES, MOLECULAR MODELING AND MOLECULAR-DYNAMICS SIMULATIONS IN THE STUDY OF THE INCLUSION COMPLEX OF THE COGNITION ACTIVATOR (+ -1-(4-METHOXYBENZOYL)-5-OXO-2-PYRROLIDINEPROPANOIC ACID (CI-933) WITH BETA-CYCLODEXTRIN/

The formation of the inclusion complex of beta-cyclodextrin with the n ew cognition activator -1-(4-methoxybenzoyl)-5-oxo-2-pyrrolidinepropan oic acid (CI-933) and the chiral discrimination capability of the macr ocyclic host towards the racemic guest were evident from H-1 NMR studi es. The structure, relative host-guest orientation and binding mode of the complex were studied using the ROESY NMR technique complemented b y molecular modelling and molecular dynamics simulations (CHARMM). All these methods converged towards the structure attained by inserting t he guest, the aromatic ring first, into the hydrophobic cavity of the host from the side of the secondary hydroxyls. Both the R- and S-enant iomers were found deeply inserted into the host, the diastereoisomeric complexes formed featuring different numbers and distribution of inte rmolecular hydrogen bonds.