Light-controlled assembly and disassembly of cyclodextrin-bisazobenzene supramolecular complexes

Abstract

The inclusion complexation of a water soluble bis-azobenzene derivative (bis-Azo) and its monotopic analog (mono-Azo) with α-, β-, and γ-cyclodextrins (CyDs) was investigated as a prototype for light-responsive self-assembling systems. Using spectroscopic techniques (UV–vis, induced circular dichroism, ¹H NMR), computational methods (molecular mechanics and dynamics), and thermodynamic analyses, we examined the photoswitching properties, stability, and structural dynamics of these systems. The azobenzene moieties in the E-isomer of mono-Azo and bis-Azo consistently showed strong affinity for the αCyD cavity, characterized by high association constants. In contrast, no complex formation was observed upon photoinduced E-to-Z isomerization. For bis-Azo, this implies the formation of supramolecular αCyD dimers, with the spatial separation between the oppositely oriented host components determined by the connector linking the two azobenzene moieties in the E-configured ditopic guest. This complex disassembles upon photoswitching, driven by the structural disruption associated with the Z-form. Both the E-and Z-isomers fitted in the cavity of βCyD, with moderate selectivity towards the E-form. A similar scenario was found for complexes with γCyD when using low concentrations of the host. Interestingly, at high concentrations γCyD formed low-solubility pseudopolyrotaxane-type supramolecular architectures with bis-Azo, which were disrupted upon Z-isomer photoisomerization. All the complexes demonstrated high fatigue resistance, maintaining structural integrity after multiple isomerization cycles. This work advances the design of stimuli-responsive preorganized supramolecular systems, with potential applications in nucleic acid delivery through dual pH/light-sensitive mechanisms.