Unraveling Solvent-Dependent Chirality Inversion in the Self-Assembly of Glutamide Amphiphiles.

This study investigates the solvent-modulated supramolecular chirality and assembly kinetics of two naphthalimide structural isomers, 18NG and 23NG, designed from glutamide derivatives linked to 1,8- and 2,3-naphthalic anhydrides, respectively. Time-dependent circular dichroism (CD) spectra reveal that 18NG exhibits chiroptical signal amplification with aging time and solvent-dependent chirality inversion: In methylcyclohexane (MCH), it forms chiral assemblies with a positive Cotton effect, whereas in dimethyl sulfoxide (DMSO), it exhibits a negative Cotton effect. FT-IR and XRD analyses demonstrate stronger amide-amide hydrogen bonds in MCH and dominant hydrophobic interaction in DMSO, where DMSO acts as both a hydrogen-bond acceptor (competing with intermolecular hydrogen bonds) and a high-polarity solvent promoting alkyl-chain aggregation. In contrast, 23NG assembles rapidly in both solvents without chirality inversion due to pre-exposed hydrogen-bonding motifs. These findings show how solvent dictates supramolecular chirality and packing by modulating noncovalent interactions, while structural isomerism governs assembly kinetics and solvent responsiveness. This work provides insights for designing adaptive chiral nanomaterials through molecular structure and solvent control.