Nanophase structuring in simple ternary solvents mediates reaction kinetics

Solvents are crucial to chemical reactivity. Ternary mixtures of water, a water-miscible polar organic solvent, and a water-immiscible oil can self-organize into nanoscale domains (nanophases), yet their impact on reaction kinetics is not well understood. Here, we investigate how nanophase structuring affects strain-promoted azide-alkyne click (SPAAC) reaction kinetics. Ternary solvents were designed to promote or suppress nanophase structuring, characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). High-throughput ultraviolet-visible spectroscopy (UV-vis) kinetics revealed that hydrophobic reactants exhibited faster rates in ternary solvents compared with pure solvents and water-containing binary mixtures. Rate enhancements were confined to a narrow region of the phase diagram containing oil-in-water nanophases and disappeared when hydrophilic reactants were used or when nanophase stability was reduced. These findings demonstrate that simple ternary solvents modulate reaction kinetics in a manner distinct from bulk solvent polarity or conventional hydrophobic effects and highlight the potential of nanophases to control reactivity.