(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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