A Supramolecular Fluorescent Chemosensor Enabling Specific and Rapid Quantification of Norepinephrine Dynamics

Host-guest supramolecular fluorescence probes have garnered significant attention in the detection and sensing of bioactive molecules due to their functionalization potential, adjustable physical properties, and high specificity. However, such probes that reliably, rapidly, and specifically measure neurotransmitter dynamics at the cellular and in vivo level have yet to be reported. Herein, we present a supramolecular fluorescent chemosensor designed for norepinephrine (NE) detection, showing an exceptional response and specificity through host-guest complexation. Multiple covalent/noncovalent interactions, molecular-folding, and confinement effect in the system synergistically enhance selectivity and accelerate reaction kinetics down to 190 ms. Our chemosensor enables real-time quantification and imaging of NE across various models including neuronal cytomembranes, brain tissues, and zebrafish. Notably, we successfully monitored NE levels in 26 brain regions of freely moving mice under fear-induced stress, revealing elevated concentrations of NE in these regions associated with emotional processing. Thus, our chemosensor is a robust tool for measuring neurotransmitter dynamics in diverse model organisms.