New cyclodextrin dimers and trimers capable of forming supramolecular adducts with shape-specific ligands

Bridged cyclodextrin dimers and trimers, in which respectively two and three hydrophobic cavities lie in close proximity, display much higher binding affinities and molecular selectivities than do parent cyclodextrins (CDs). By joining betaCD units with links inserted at different positions (2-2', 3-2', 6-2' or 6-2'-6'') and interposing spacers of different lengths and shapes, multicavity structures can be synthesized that are precisely tailored to fit specific guest molecules. This enzyme-mimicking strategy can also be used to generate stable supramolecular adducts. A series of CD dimers and trimers was prepared in good yields by carrying out the critical synthetic steps under power ultrasound (US) or microwave (MW) irradiation. Starting from azide and acetylenic CD derivatives, we exploited an efficient MW-promoted Huisgen 1,3-dipolar cycloaddition in the presence of Cu(I) salts. The resulting bridged CD derivatives gave stable adducts with magnetic-resonance-imaging contrast agents (MRI CAs) containing gadolinium(III) chelates. These inclusion complexes were found to be 2 to 3 orders of magnitude more stable than those formed by betaCD and to be endowed with high relaxivity values.