A Novel Merocyanine Derivative for Probing Polarity at Cubosome Interfaces

Abstract This study reports the development of a synthetic route for the chemical environment sensor C10SP, designed for incorporation into phytantriol‐based cubosomes. The molecule combines an apolar aliphatic tail for lipid bilayer anchoring with a polarity‐sensitive chromophore. Strategic steps, including tertiary amine‐mediated amidation to covalently attach the tail and controlled nitrogen methylation to form the iminium moiety within the indolenine scaffold, enabled the successful synthesis of C10SP. The photophysical analysis demonstrated that stabilizers intercalating into lipid bilayers reduce the polarity of cubosome aqueous channels by constraining lipid headgroup interactions with water, while non‐intercalating stabilizers have no effect. These findings underscore the potential of C10SP as a sensor for the polarity of lipid‐water interfaces, while also emphasizing the promise of cubosome aqueous channels as tunable environments for biological reactions sensitive to medium polarity.