Light-switchable azobenzene-linked bis-β-cyclodextrin dimers as platforms for cationizable supramolecular amphiphiles

Two bis-β-cyclodextrin derivatives linked through an azobenzene spacer—one bearing native β-cyclodextrin ((βCyD) 2 -azo) and the other, the fully methylated counterpart ((MeβCyD) 2 -azo)—were investigated using UV–Vis, circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and molecular modeling. Both undergo self-dimerization in aqueous solution, as evidenced by a characteristic exciton coupling (EC) signal in the CD spectra and a concentration-dependent loss of spectral resolution in NMR. NMR data also confirmed that aggregation occurred without self-inclusion into the cyclodextrin (CyD) cavities, excluding major conformational rearrangements. Their supramolecular behavior under photoisomerization was systematically examined by varying concentration, temperature, solvent polarity, and competitive guests. Spectroscopic and computational results support a model in which dimerization arises from intermolecular azobenzene–azobenzene π–π stacking in a sandwich-type arrangement, together with other hydrophobic interactions. In the case of the (MeβCyD) 2 -azo derivative, additional inter-dimer hydrophobic contacts promote hierarchical self-assembly into helical supramolecular oligomers at higher concentrations, as revealed by TEM, while remaining in fast equilibrium with the corresponding supramolecular dimers. The addition of a charged adamantane guest induces disaggregation: the EC signal vanishes for (βCyD) 2 -azo, whereas (MeβCyD) 2 -azo shows only partial attenuation, reflecting its greater aggregate stability. This disassembly is driven by electrostatic repulsion between charged ternary complexes. Finally, the complexation of both bis-β-cyclodextrin derivatives with an adamantane derivative containing three ionizable cationic tails (Ada-3NH 3 + ) was also studied as a prototype for the formation of ternary supramolecular complexes, offering a potential platform for the future exploration of nucleic acids nanocondensation.