Solvent-Induced Stereomutation in Supramolecular Assemblies Explained by Hansen Solubility Parameters

Solvent-induced stereomutation, the reversal of supramolecular helicity driven by solvent identity, is a striking yet poorly understood phenomenon in supramolecular chemistry, with implications for chiral materials, molecular recognition, and functional assemblies. Despite numerous observations in diverse systems, a general framework for understanding and controlling such helicity inversion between supramolecular diastereomers remains elusive. Here, we present a quantitative strategy based on Hansen solubility parameters (HSPs) that identifies distinct and reproducible solvent regimes associated with opposite helicities in two structurally different chiral monomers: a C₂-symmetric perylene diimide derivative (S-PDI) with chiral citronellol side chains attached through gallate wedges, and a C₃-symmetric truxenone derivative (S-TTA) bearing the same chiral side chains connected via hydrogen-bonding amides. By mapping supramolecular handedness within the HSP space, we show that helicity arises not only from molecular structure but also from the interplay between solvent dispersion, polarity, and hydrogen-bonding, which modulate the solvation of side chains and influence the geometry of aromatic stacking. Furthermore, the helicity induced by the solvent environment is not a result of variations in the assembly pathway and is independent of concentration. These results establish HSP mapping as a general strategy for explaining the opposite supramolecular chirality controlled by the solvent and for designing adaptive, reconfigurable, and functional chiral materials.