(E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles as efficient Michael acceptors for cysteine: Real application in biological imaging

•Three heteroarylacrylonitriles-derived fluorescent probes were synthesized.•Three heteroarylacrylonitriles-derived fluorescent probes were assessed as Michael acceptors toward cysteine.•New compounds for cysteine detection are reported.•New probes for cysteine detection localize preferentially at the cytoplasm and endosomes of living cells.

(E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles derivatives (compounds 1, 2, and 3) were synthesized and assessed for their ability to recognize cysteine (Cys) in aqueous solution via a Michael-type reaction.The sensors can be used for the quantification of Cys with detection limits of ca. 10−5 M. The sensors showed excellent selectivity for Cys over other amino acids. The most reactive five-membered heterocyclic substituent in the tested compounds was the isoxazole derivative (compound 2). The reactivity study was complemented with a theoretical analysis based on the global electrophilicity and hardness. Interestingly, both descriptors correctly assign the reactivity trend 2 > 1 ≈ 3, in accordance with the experimental evidence. Finally, these sensors were successfully applied to the fluorescence imaging of intracellular Cys in SH-SY5Y cells.

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