Solvent heterogeneity regulates assembly pathways in supramolecular polymerization

Abstract Supramolecular polymers are fundamental mimics of biological assemblies with diverse functions. However, predicting monomer solubility and controlling the colloidal stability of the resulting assemblies in solution remain major challenges. As a result, their preparation commonly relies on solvent mixtures, which can generate local heterogeneities during sample processing—an effect that remains poorly understood. Here, we demonstrate that solvent heterogeneity biases assembly pathways in supramolecular polymerization, with the extent of this effect modulated by monomer structure. Using an amphiphilic Pd(II) complex as a model system, we uncover a thermally accelerated transition from kinetically controlled discrete nanostructures to thermodynamically stable supramolecular polymers in water/1,4-dioxane mixtures. Combined experimental and theoretical analyses reveal that this transformation is mediated by microscopic liquid–liquid phase separation within the mixed solvent, creating 1,4-dioxane-enriched microdomains with increased local monomer concentration. Thermal annealing enhances molecular mobility and promotes the growth and coalescence of these microdomains, facilitating the transition to one-dimensional fibers. Extending the investigation to structurally related monomers further identifies the metal center and hydrogen-bonding motifs as key design elements governing this behavior. By linking molecular design and solvent heterogeneity to pathway complexity, our findings highlight how mixed solvents can be used to control supramolecular polymerization.