Bright and Versatile Azetidinecarboxamide-Based Fluorophore–Ligand Conjugates for High-Resolution Cell Imaging

Abstract

Fluorophore–ligand conjugates play a pivotal role in cellular imaging, providing high target specificity. However, simultaneously achieving conjugates with high brightness and ligand-targeting diversity presents significant challenges. Traditional strategies often require complex, multistep modifications for fluorophore enhancement and ligand conjugation. Here, we present an azetidinecarboxamide strategy that addresses these challenges by integrating brightness enhancement and ligand conjugation capabilities within a single molecular framework. The azetidinecarboxamide core suppresses twisted intramolecular charge transfer (TICT), thereby enhancing fluorescence quantum yield. Its carbonyl group provides a versatile site for conjugating a wide range of targeting ligands, enabling the rapid development of diverse and tunable fluorophore–ligand conjugates. This streamlined approach reduces synthetic complexity, accelerates probe development, and is compatible with a wide variety of fluorophores, such as coumarin, naphthalimide, NBD, rhodol, rhodamine, and silicon–rhodamine, facilitating the creation of high-performance, multifunctional probes for advanced cellular imaging.