Work

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

Year: 2025

Type: preprint

Abstract: 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.

Source: ChemRxiv

DOI: 10.26434/chemrxiv-2025-t8fr3

Authors: Luis M. Negrón, Yazmary Meléndez-Contés, Jose Rivera

Institution: University of Puerto Rico System

Language: English

Topic: Supramolecular Chemistry and Complexes

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute on Minority Health and Health Disparities

Awards: Small Molecule Self-Assembly in Aqueos Media, COBRE Phase 2: Center for Neuroplasticity at the University of Puerto Rico, Center for Collaborative Research in Health Disparities, Support for University Biomedical Excellence at UPR-RP