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 π-π 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 (T_cp) and a hydrophobic collapse-induced solid precipitate above T_cp, 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.