Exploring flavylium-based SWIR emitters: Design, synthesis and optical characterization of dyes derivatized with polar moieties

• Published in: Bioorganic chemistry 2024-07, Vol.148, p.107462-107462, Article 107462
• Main Authors: Blua, Federica, Boccalon, Mariangela, Rolando, Barbara, Napolitano, Roberta, Arena, Francesca, Blasi, Francesco, Bertinaria, Massimo
• Format: Article
• Language: English
• Subjects: Flavylium fluorophores; Optical imaging; Polymethine dyes; Shortwave infrared; SWIR emitters
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107462

[Display omitted] •A series of flavylium polymethine derivatives of Flav7 was designed and synthesized.•Optical characterization of the new fluorophores was carried out.•New SWIR emitters were obtained, with FlavMorpho selected as the best compound.•The best SWIR emitter, FlavMorpho, was encapsulated in phosholipidic micelles.•FlavMorpho micelles emission was higher than Flav7 and ICG, exciting at their λmax. Imaging in the shortwave infrared (SWIR, 1000–1700 nm) region is gaining traction for biomedical applications, leading to an in-depth search for fluorophores emitting at these wavelengths. The development of SWIR emitters, to be used in vivo in biological media, is mostly hampered by the considerable lipophilicity of the structures, resulting from the highly conjugated scaffold required to shift the emission to this region, that limit their aqueous solubility. In this work, we have modulated a known SWIR emitter, named Flav7, by adding hydrophilic moieties to the flavylium scaffold and we developed a new series of Flav7-derivatives, which proved to be indeed more polar than the parent compound, but still not freely water-soluble. Optical characterization of these derivatives allowed us to select FlavMorpho, a new compound with improved emission properties compared to Flav7. Encapsulation of the two compounds in micelles resulted in water-soluble SWIR emitters, with FlavMorpho micelles being twice as emissive as Flav7 micelles. The SWIR emission extent of FlavMorpho micelles proved also superior to the tail-emission of Indocyanine Green (ICG), the FDA-approved reference cyanine, in the same region, by exciting the probes at their respective absorption maxima in phosphate buffered saline (PBS) solution. The availability of optical imaging devices equipped with lasers able to excite these dyes at their maximum of absorption in the SWIR region, could pave the way for implemented SWIR imaging results.