G-Quadruplex Supramolecular Polymers with Unusual Phase Transitions

Abstract

Supramolecular polymers (SPs) are non-covalent analogues of conventional polymers, constructed from small molecular monomers interconnected through directional and reversible interactions.1 These weak yet cooperative interactions give rise to one-dimensional molecular assemblies that are inherently dynamic and responsive to external stimuli. In this talk, I will focus on aqueous SPs and discuss our recent advances in metal-ion-induced G-quadruplex-based SPs2,3,4 that exhibit unusual thermos-responsiveness and phase transitions in water. We report, for the first time, that Cu⁺ ions can guide guanosine (G) to form an exceptionally stable G-quadruplex, distinct from the well-known K⁺-stabilized G-quadruplex, a non-canonical DNA secondary structure.2 The resulting G4·Cu⁺ self-assembles in water through a combination of π–π stacking, metallophilic interactions, and hydrophobic effects to form thermally robust SPs. The aqueous SP solution undergoes heating-induced unusual phase transitions. Below the cloud point temperature, dehydration-driven crosslinking of SPs leads to hydrogel formation, while above cloud point a hydrophobic collapse produces a cloudy precipitate, reflecting an apparent lower critical solution temperature (LCST)-type behavior.2 Notably, these G4·Cu⁺ supramolecular polymers and gels remain stable over both higher and lower temperature ranges, suggesting a possible overlap of LCST- and UCST-type transitions. By introducing suitable good cosolvents as molecular regulators, the enthalpic and entropic contributions governing these transitions can be decoupled. The cosolvent shifts the UCST and LCST boundaries in opposite directions, revealing an intermediate temperature window in which the system exists as a monomeric sol. In water–cosolvent mixtures, the supramolecular polymer forms a gel at room temperature, dissociates into a sol around ~50 °C, and re-polymerizes into a gel above ~80 °C, analogous to sequential UCST- and LCST-like behaviors. Beyond Cu⁺, we also demonstrate that dimercury(I) induces the formation of a highly stable octameric G-quadruplex, G8·Hg2²⁺. This assembly undergoes J-type stacking to generate SPs and gels with superior resistance to aging, dilution, and temperature compared to conventional G4·K⁺ gels.3 These aqueous G-quadruplex SPs with programmable phase transitions open new opportunities for smart materials in materials science, and reconfigurable biomaterials.