Exclusive Cupric Ion Specificity of Gel–Sol Transition Enables Efficient Sensing and Therapeutic Delivery

Specific molecular recognition offers remarkable selectivity found in biological systems. Hydrogels exhibit fascinating properties including phase transition, wherein gel-to-sol transition through specific metal ion recognition has been nonexistent. An unexpected Cu(II)-induced disassembly of a G-quadruplex hydrogel into a sol state rapidly (in minutes) is presented, which is solely specific to cupric ions. The hydrogelator components, guanosine, and phenylboronic acid, bind cupric ions much more strongly than any other metal ions, causing disruption of the well-ordered Hoogsteen-type hydrogen-bonded G-quadruplex network structure selectively by Cu(II). The synergistic dual recognition is further facilitated by C─C coupled biphenyl production, providing a favorable driving force for the gel disruption. The utility of the specific recognition-mediated gel degradation is demonstrated in detecting cupric ions with high sensitivity (≈1 µm), even in real-world samples, including spiked human serum. It is effectively translated into a paper-based point-of-care device. Further, leveraging the specificity of the phase transition, the sustained delivery of a model drug (Levodopa) is showcased in response to Cu(II), which gets upregulated in certain neurodegenerative diseases. Altogether, this discovery of the dual molecular recognition-guided gel-to-sol transition offers a robust platform for specific detection, imaging, and therapeutic delivery, besides enriching the fundamental scientific advancement of G-quadruplex-based hydrogel chemistry.