Kinetic and Thermodynamic Control of G-Quadruplex Polymorphism by Na⁺ and K⁺ Cations

G-Quadruplexes (G4s) are ubiquitous nucleic acid folding motifs that exhibit structural diversity that is dependent on cationic conditions. In this work, we exploit temperature-controlled single-molecule fluorescence resonance energy transfer (smFRET) to elucidate the kinetic and thermodynamic mechanisms by which monovalent cations (K+ and Na+) impact folding topologies for a simple G-quadruplex sequence (5′-GGG-(TAAGGG)3-3′) with a three-state folding equilibrium.