RESUMO
Norepinephrine (NE) is a key neurotransmitter in the central and sympathetic nervous systems, whose content fluctuates dynamically and rapidly in various brain regions during different physiological and pathophysiological processes. However, it remains a great challenge to directly visualize and precisely quantify the transient NE dynamics in living systems with high accuracy, specificity, sensitivity, and, in particular, high temporal resolution. Herein, we developed a series of small-molecular probes that can specifically detect NE through a sequential nucleophilic substitution-cyclization reaction, accompanied by a ratiometric near-infrared fluorescence response, within an impressively short time down to 60 ms, which is 3 orders of magnitude faster than that of present small-molecular probes. A unique water-promoted intermolecular proton transfer mechanism is disclosed, which dramatically boosted the recognition kinetics by â¼680 times. Benefiting from these excellent features, we quantitatively imaged the transient endogenous NE dynamics under external stimuli at the single living neuron level and further revealed the close correlations between NE fluctuations and Parkinson's disease pathology at the level of acute brain slices and live mouse brains in vivo.
Assuntos
Encéfalo , Norepinefrina , Animais , Camundongos , Encéfalo/diagnóstico por imagem , Sondas Moleculares , Imagem Óptica , NeurôniosRESUMO
Norepinephrine (NE) is a key neurotransmitter in the central nervous system of organisms; however, specifically tracking the transient NE dynamics with high spatiotemporal resolution in living systems remains a great challenge. Herein, we develop a small molecular fluorescent probe that can precisely anchor on neuronal cytomembranes and specifically respond to NE on a 100-ms timescale. A unique dual acceleration mechanism of molecular-folding and water-bridging is disclosed, which boosts the reaction kinetics by Ë105 and Ë103 times, respectively. Benefiting from its excellent spatiotemporal resolution, the probe is applied to monitor NE dynamics at the single-neuron level, thereby, successfully snapshotting the fast fluctuation of NE levels at neuronal cytomembranes within 2 s. Moreover, two-photon fluorescence imaging of acute brain tissue slices reveals a close correlation between downregulated NE levels and Alzheimer's disease pathology as well as antioxidant therapy.
Assuntos
Doença de Alzheimer , Norepinefrina , Humanos , Doença de Alzheimer/diagnóstico por imagem , Neurônios , Imagem ÓpticaRESUMO
Stereoselective ß-C(sp2)-H alkylation of enamides with redox-active N-hydroxyphthalimide esters via a photoredox-catalyzed decarboxylative cross-coupling reaction is demonstrated. This methodology features operational simplicity, broad substrate scopes, and excellent stereoselectivities and functional group tolerance, affording a diverse array of geometrically defined and synthetically valuable enamides bearing primary, secondary or tertiary alkyl groups in satisfactory yields.