β‐Cyclodextrin PAMAM Dendrimer: How to Overcome the Tumbling Process for Getting Fully Available Host Cavities

The synthesis of a G0 polyamidoamide (PAMAM) dendrimer end‐capped with four β‐cyclodextrin (β‐CD) units, named as Tetra‐CD was performed by using copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC). This new platform presents a considerable high water‐solubility in comparison to native β‐CD. Tumbling process involving half of the CD cavities in D2O was evidenced by 1H NMR spectroscopy. Interaction of adamantane with Tetra‐CD has been fully investigated by 1D/2D NMR techniques and mass spectrometry besides a joint study on new β‐CD monomers (named as A and B) and on a dimer (Di‐CD) and a trimer (Tri‐CD). The obtained results demonstrate that the tumbling effect can be shifted in the presence of an appropriate hydrophobic guest resulting in the full host‐ability of the CD units in water for that guest. A G0 PAMAM dendrimer bearing four β‐cyclodextrin cavities is synthesized through click chemistry. From the results of 1H NMR studies and mass spectrometry analyses, it is demonstrated that the complexation strength of adamantyl species with cyclodextrin is favourable to the full availability of the cavities in water, despite of a spontaneous tumbling process in that medium for the pristine platform.