Crystal structures and molecular dynamics studies of the inclusion compounds of β-citronellol in β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin

The crystal structures of the inclusion complexes of the beta-citronellol (cl) in beta-Cyclodextrin (beta-CD), heptakis(2,6-di-O-methyl)-beta-Cyclodextrin (DM-beta-CD) and heptakis(2,3,6-tri-O-methyl)-beta-Cyclodextrin (TM-beta-CD) have being investigated by X-ray crystallography. The cl/beta-CD inclusion complex crystallizes in the P1space group forming dimers which are arranged along the c-axis according to the Intermediate Channel packing mode. Inside the dimeric host cavity two enantiomeric guest molecules are accommodated. The inclusion complexes of cl/DM-beta-CD and cl/TM-beta-CD crystallize in the P2(1)2(1)2(1) space group having both 1:1 guest:host stoichiometry, the guest found always with the (-)-cl enantiomeric configuration. The guest is fully encapsulated inside the DM-beta-CD host cavity whereas is partially encapsulated in the TM-beta-CD which is severely puckered as in all TM-beta-CD complexes and its primary side is efficiently blocked by the methoxy groups. The complex units in the case of cl/DM-beta-CD pack along the crystallographic a-axis in a head-to-tail manner forming columns of herringbone mode whereas in the case of cl/TM-beta-CD are arranged also head-to-tail, parallel to the b-axis, in a screw-channel mode. MD simulations based on the determined crystal structures showed that in a simulated aqueous environment the guest maintains the inclusion mode observed crystallographically in every case. MM/GBSA-calculations used for comparison of the inclusion complexes binding affinity with each other, indicated that the inclusion of beta-citronellol in TM-beta-CD is less favorable than in beta-CD and DM-beta-CD. (c) 2018 Elsevier B.V. All rights reserved.