Programmable Host–Guest Recognition for Shape-Shifting Supramolecular Nanostructure States

The ability to design nanostructures with programmable and reversible morphological transformations is essential for advancing supramolecular chemistry toward functional biomaterials. Here, a pH-sensitive supramolecular system is shown comprising a peptide amphiphile functionalized with carboxylate-terminated bicyclo[2.2.2]octane (BO) guest molecules along with a cucurbit[7]uril (CB[7]) host modified with a pendant PEG chain. This system enables dynamic transitions among three nanostructure states: filamentous nanofibers, spherical micelles, and nanoscale aggregates. These transitions are governed by pH-dependent CB[7]-BO complexation, which modulates the hydrophilic-lipophilic balance and steric repulsion of the self-assembling units. The nanostructure transformations are reversible, allowing control over nanostructure states by adjusting pH and component mixing ratio. Furthermore, these transitions can be triggered autonomously using an enzymatic pH control mechanism, enabling transient morphological changes. This work highlights the potential of integrating multiple supramolecular motifs to create dynamic, programmable, and switchable nanomaterials with life-like structural transience.