Experimental and computational study of the complexation of adamantyl glycosides with β-cyclodextrin

Complexation of α- and β-anomers of adamantyl galactosides and adamantyl mannosides, having different configuration of the chiral linker connecting the sugar and the adamantamine (AMA) subunits, with β-cyclodextrin (β-CD) was investigated by means of NMR spectroscopy, microcalorimetric titrations and computational studies. The synthesis of adamantyl galactosides is also reported. The experimental investigations are consistent with the formation of 1:1 complexes in which the hydrophilic part of the guest protruded out of the secondary rim. The β-cyclodextrin was shown to be a rather efficient binder for the examined guests in water, primarily as a consequence of the enthalpically favourable inclusion of the adamantyl moiety within the hydrophobic cavity of the host. The structures of AMA derivatives complexes were modelled by combination of molecular and quantum mechanics - B3LYP/6-31G(d) in implicitly modelled water (PCM). The differences in the stability of primary and secondary complexes were observed. The main reasons for that could be more pronounced dehydration of the hydrophilic part of the guest upon complete adamantane inclusion in the complexes of primary type and the different hydrogen bonding pattern at the primary and secondary CD rims.