Dopamine (DA) is a pivotal neurotransmitter whose spatiotemporal dynamics are fundamentally linked to a myriad of neurological processes and disorders. Despite its significance, real-time visualization of DA across diverse cellular states remains challenging due to the scarcity of biocompatible and high-fidelity sensing strategies. Herein, we report a novel, trace Cu²⁺-catalyzed oxidative fluorogenic assay for the selective imaging of DA in living cells. By harnessing a trace copper-mediated redox cycle to catalyze DA oxidation, followed by specific fluorogenic recognition with 8-hydroxyjulolidine, this strategy circumvents the limitations of conventional oxidant-dependent approaches. The method yields a robust fluorescence response at 510 nm and maintains exceptional sensitivity and selectivity for DA over other catecholamines and biological interferents under physiological conditions. Notably, the strategy enabled the successful detection of endogenous DA dynamics in PC12 cells under normal, inflammatory, and depressive conditions. Time-lapse imaging revealed significantly suppressed DA release and altered DA reuptake kinetics in depressive cell models. This work provides a powerful analytical tool for elucidating the complex physiological and pathological roles of DA in neural systems.
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