A cofactor mediated supramolecular oligo-adenine triplex for reprogrammable macroscopic hydrogel assembly

Noncanonical DNA structures mediated by low-molecular-weight cofactors significantly enrich the arsenal of the DNA toolbox and expand its functional applications. In this study, cyanuric acid (CA), a cofactor with three thymine-like edges, is employed to assemble adenine-rich strands (A-strands) into a parallel noncanonical A-CA triplex configuration through Watson-Crick and Hoogsteen interactions. This assembly occurs at a system pH value below the p<i>K</i>_a of the CA cofactor (6.9), where CA is protonated, while its deprotonation at higher pH levels leads to the dissociation of the A-CA triplex into single A-strands and free CA cofactors. The structural transition is fully pH reversible. The A-CA triplex is further utilized as a crosslinking element for reprogrammable macroscopic object assembly, exemplified by hydrogel cubes (5 × 5 × 5 mm), a topic that has been less explored compared to nano- and microscopic constructs. Controlled, modular assembly and disassembly of various configurations, such as square, line, and T-shape, are demonstrated through reversible pH adjustments. This strategy offers a streamlined approach using a single DNA sequence and cofactor for hydrogel modification and complex construction, providing cost-effective, recyclable, and stimuli-responsive functionality, which inspires the development of versatile and adaptive supramolecular systems in chemistry and materials science.