Synthesis and characterization of benzotriazolyl acrylonitrile analogs-based donor-acceptor molecules: Optical properties, in vitro cytotoxicity, and cellular imaging

• Published in: Dyes and pigments 2021-05, Vol.189, p.109251, Article 109251
• Main Authors: Hernández-Fernández, Eugenio, Ortega-Villarreal, Ana Sofia, García-López, Ma. Concepción, Chan-Navarro, Rodrigo, Garrard, Samuel, Valdivia-Berroeta, Gabriel A., Smith, Stacey J., Christensen, Kenneth A., Michaelis, David J.
• Format: Article
• Language: English
• Subjects: Acrylonitrile analogs; Benzotriazole; Cellular imaging; Confocal microscopy; Lysosome/endosome staining
• ISSN: 0143-7208; 1873-3743
• DOI: 10.1016/j.dyepig.2021.109251

A series of eight new (E)-benzotriazolyl acrylonitrile derivatives were synthesized under reflux conditions via Knoevenagel condensation between acetonitrile analogs and a short series of aromatic aldehydes. X-ray diffraction analysis for one of the compounds was performed to determine the (E)-geometry of its double bond. The photoluminescent properties of all compounds in solution were also evaluated. These compounds exhibit strong blue, green and yellow emission under ultraviolet light excitation with fluorescence quantum yield in the 0.08–0.58% range. To determine the suitability of these compounds for use in cell-based analysis, cytotoxicity assays were performed on a representative molecule using a common mammalian cell line (HEK 293T cells) at different concentrations. The results showed limited toxicity (72 ± 16% viability) at the highest concentration tested (50 μM). Finally, confocal microscopy demonstrated that our compound was internalized into cells and localized to endosomes and/or lysosomes in a similar fashion to Dextran–Cascade Blue (DCB). [Display omitted] •A series of benzotriazolyl acrylonitriles with D-A systems were prepared.•The (E)-geometry of the double-bond was confirmed by X-ray analysis.•Compounds showed interesting photophysical properties for bioimaging.•Selected compound presented low cytotoxicity in HEK 293T cell line.•Benzotriazolyl acrylonitriles can be considered safe cell-based fluorescent markers.