Imidazo[1,2-a]pyridine-based hybrids. Copper-catalyzed cycloaddition synthesis, photophysics, docking, and interaction studies with biomacromolecules

• Published in: Dyes and pigments 2023-06, Vol.214, p.111212, Article 111212
• Main Authors: Lopes, Eric F., Saraiva, Maiara T., Debia, Natalí P., Silva, Luana, Chaves, Otávio A., Stieler, Rafael, Iglesias, Bernardo A., Rodembusch, Fabiano S., Lüdtke, Diogo S.
• Format: Article
• Language: English
• Subjects: Biomolecules; Carbohydrates; Click chemistry; ESIPT; imidazo[1,2-a]pyridine; Optical sensor
• ISSN: 0143-7208; 1873-3743
• DOI: 10.1016/j.dyepig.2023.111212

Herein, we report the connection between imidazo[1,2-a]pyridines with several biologically relevant molecules. The strategy used to build these connections was based on a copper-catalyzed cycloaddition, where different azides and imidazo[1,2-a]pyridine moieties bearing an alkyne were used in this transformation. In total, 8 imidazo[1,2-a]pyridines bearing a terminal alkyne could be synthesized, thus, allowing for the synthesis of 27 new hybrid molecules connected by a triazole ring. In addition 17 imidazo[1,2-a]pyridines connected to either carbohydrate or naturally originated molecules were also prepared. Based on their electronic structure, two examples based on the benzothiazole moiety were selected for fluorescence and binding studies. These compounds show absorption maxima in the UV region, ascribed to 1π-π* electronic transition. The presence of an additional hydroxyl group in one compound allowed a completely different photophysical behavior, where a dual fluorescence emission could be observed, related to the ESIPT process. Spectroscopic studies by UV–Vis, steady-state fluorescence, and molecular docking calculations evidenced the ability of each derivative to establish interactions with CT-DNA and human and bovine serum albumins (HSA, and BSA, respectively). The behavior presented for this new class of compounds makes them a promising tool as optical sensors for biomacromolecules. •Synthesis of synthetical handles based on Imidzo[1,2-a]pyridines.•Copper-catalyzed cycloaddition for the synthesis of the most diverse triazoles containing imidazo[1,2-a]pyridines.•Photophysical experiments for selected examples.•Comparison between an ESIPT and non-ESIPT fluorophore.•DNA and BSA interaction studies using UV–Vis absorption, steady-state fluorescence emission, and molecular docking.