Noradrenaline-Specific, Efficient Visualization in Brain Tissue Triggered by Unique Cascade Nucleophilic Substitution.

Noradrenaline as one of the most important neurotransmitters in the sympathetic nervous system plays key roles in all of the forebrain activities such as perception, memory, learning, and homeostasis, and its dysfunction is closely related to both neurodegenerative diseases and central nervous system disorders. The very similar structures and properties of the three coexisting catecholamine neurotransmitters-dopamine, epinephrine, and noradrenaline-make it almost impossible to design fluorescent probes that respond specifically to noradrenaline, which restricted its physiological and pathological studies greatly. Fantastic design turned dreams into reality in this work: the cascade nucleophilic substitution reactions between noradrenaline and fluorophore coupling carbonic ester, which formed a five-membered ring catechol-containing compound with the release of the fluorophore accompanied by unique fluorescent responses, allowed us to develop a fluorescent probe to detect and visualize noradrenaline over dopamine and epinephrine in brain tissue. Instead of the noradrenaline synzyme immunofluorescence labeling path, the present fluorescent probe can visualize noradrenaline directly with comparable specificity.