Cu(I)‐Induced G‐quartets: Robust Supramolecular Polymers Exhibiting Heating‐Induced Aqueous Phase Transitions into Gel or Precipitate

Certain proteins and synthetic covalent polymers experience aqueous phase transitions, driving functional self-assembly. Herein, we unveil the ability of supramolecular polymers (SPs) formed by G4.Cu+ to undergo heating-induced unexpected aqueous phase transitions. For the first time, guided by Cu+, guanosine (G) formed a highly stable G-quartet (G4.Cu+)/G-quadruplex as a non-canonical DNA secondary structure with temperature tolerance, distinct from the well-known G4.K+. The G4.Cu+ self-assembled in water through p-p stacking, metallophilic and hydrophobic interactions, forming thermally robust SPs. This enhanced stability is attributed to the stronger coordination of Cu+ to four carbonyl oxygens of G-quartet and the presence of Cu+---Cu+ attractive metallophilic interactions in Cu+-induced G-quadruplex, exhibiting a significantly higher interaction energy than K+ as determined computationally. Remarkably, the aqueous SP solution exhibited heating-induced phase transitions-forming a hydrogel through dehydration-driven crosslinking of SPs below cloud temperature (Tcp) and a hydrophobic collapse-induced solid precipitate above Tcp, showcasing a lower critical solution temperature (LCST) behavior. Notably, this LCST behavior of G4.Cu+ SP originates from biomolecular functionality rather than commonly exploited thermo-responsive oligoethylene glycols with supramolecular assemblies. Furthermore, exploiting the redox reversibility of Cu+/Cu2+, we demonstrated control over the assembly and disassembly of G-quartets/G-quadruplex and gelation reversibly.