Investigation of the conformational behaviour of permethylated cyclodextrins by molecular modelling

Conformations of manually built native and permethylated α-, β- and γ-cyclodextrins (CD) were investigated using various computer assisted molecular modelling methods. Calculations were carried by applying the MM + and the Tripos force field. The influences of atomic charges on the macrocyclic conformations during the optimization procedure were analyzed. The permethylation of hydroxyl groups of cyclodextrins changes bond and torsion angles between the glucose monomers and of the primary substituents. A method to determine the diameters of the cyclodextrin cavity by a modelling approach is described. It is shown that due to permethylation the larger cavity opening is increased and the primary substituents are canted outwards. As a consequence, the torus shape of the molecule changes, which is an important feature for docking and fitting studies.