Imidazolinone-based fluorophores: from Green Fluorescent Proteins to confinement strategies and bioinspired materials design

Abstract

Fluorescent proteins, such as the Green Fluorescent Protein (GFP) discovered in Aequorea victoria, have revolutionized biological researches. Their fluorescence is primarily governed by a dye containing an imidazolinone motif that is buried within the protein core, as well as by its stabilization by the surrounding protein scaffold. Inspired by this structure-property relationship, researchers have developed synthetic imidazolinone-based dyes and engineered confined environments that emulate the folded protein cage. These complementary strategies overcome key limitations of the isolated natural dyes, including low brightness and quenching via twisted intramolecular charge transfer (TICT). This review examines the structural and photophysical properties of unnatural imidazolinone-based dyes, as well as the role of confinement in modulating their fluorescence. We compare covalent and non-covalent confinement approaches, highlighting their effects on brightness, stability, and functional versatility. Finally, we discuss emerging applications in imaging, sensing, photocatalysis, phototherapy, and optical devices. We also outline the challenges and opportunities of advancing confined imidazolinone fluorophores beyond natural protein frameworks.