Protonation-Induced Octamer–Hexadecamer Transition in Multiresponsive Supramolecular G-Quadruplexes

Ionization-induced supramolecular assembly remains a rare and mechanistically intriguing phenomenon in soft matter design. Here, we report a pH-responsive system in which guanosine derivatives bearing imidazole moieties undergo a reversible transformation from discrete octameric to hexadecameric G-quadruplex structures upon protonation. This structural transition leads to the formation of multiresponsive supramolecular particles capable of encapsulating and releasing small-molecule cargo in response to acidic stimuli. Spectroscopic, calorimetric, and computational studies reveal the energetic and conformational basis for this transition, establishing a direct link between ionization events, supramolecular topology, and emergent function. These findings demonstrate a new strategy for programming responsive behavior into guanosine-based assemblies and expand the design toolbox for pH-triggered delivery platforms.