Cu(I)-Induced G-Quadruplex: Reentrant Supramolecular Polymerization with UCST Gel–Sol–LCST Gel Transitions

Abstract

Aqueous phase transitions governed by upper and lower critical solution temperatures (UCST/LCST) are fundamental to (bio)macromolecular self-assembly, yet reproducing such behavior in supramolecular polymers (SPs) remains challenging because of their dynamic, solvent-sensitive nature. Here, we report Cu+-induced G-quadruplex (G4·Cu+) supramolecular polymers that self-assemble in water through π–π stacking, Cu+ coordination, Cu+···Cu+ metallophilic interactions and hydrophobic forces. In water, the system exhibits LCST-like behavior, undergoing dehydration-driven gelation below the cloud point followed by hydrophobic collapse into a precipitated phase at higher temperatures. The strong Cu+-stabilized assembly causes enthalpic (UCST-like) and entropic (LCST-like) polymerization contributions to overlap, masking the individual transitions. By introducing good cosolvents, these competing transitions are separated, revealing reentrant gel–sol–gel phase behavior under monotonic heating. At low temperature, solvent-solvent interaction-driven cononsolvency reduces polymer solubility, forming a crosslinked UCST-like gel. Upon heating, disruption of solvent-solvent interactions generates a monomeric sol, while further heating induces solvophobic collapse and reassembly into an LCST-like gel. This minimalistic supramolecular system demonstrates solvent-controlled reentrant thermal phase transitions and provides a general strategy for engineering thermally adaptive and reconfigurable supramolecular biomaterials.