Breaking the Photostability and pH Limitation of Halo‐Fluoresceins through Chitosan Conjugation

Halo‐fluoresceins are widely used in cell and tissue staining, intracellular sensing, and photodynamic therapy, but their notorious photo‐instability and pH dependence restrict their applications, especially in long‐term visible light exposure and acidic environments. To overcome these limitations, here a strategy is proposed of conjugating chitosan with the carboxyl group of halo‐fluorescein (CS‐halofluorescein). The cross‐linked polymer chains and the hydrogen‐bonding networks of chitosan help shielding out 1O2 from direct attacking the encapsulated halo‐fluoresceins, leading to a two orders of magnitude lower photobleaching rate. Meanwhile, the condensation of primary amines of chitosan with the carboxyl group on halo‐fluorescein blocks the pH‐dependent intramolecular spirocyclization, leading to pH‐inert fluorescein derivatives. The greatly improved photostability and pH inertness of CS‐halofluoresceins can be harvested for aerobic photoredox synthesis and photodynamic bacteria inactivation in extremely acidic media. Moreover, food additive nature of chitosan and erythrosine (TIF) and excellent film‐forming property of chitosan allow coating‐based light‐assisted preservation of perishable fruits, leading to appreciably extended shelf life of fruits (e.g., perishable strawberry, rt: > 3 days; 4 °C: > 5 days). Halo‐fluoresceins are famous for various applications, such as photoredox synthesis, photodynamic therapy, and sensing and imaging, but suffer from notorious photo‐instability and pH dependence, which limit their applications in long‐term light exposure and acidic environments. Herein, a chitosan conjugation strategy is proposed for significantly increasing the anti‐photobleaching activity and pH inertness of halo‐fluoresceins, endowing these old dyes with new vitality.