Mahdi Chaari,Nerea Gaztelumendi,Justo Cabrera-González, Paula Peixoto-Moledo,Clara Viñas, Elba Xochitiotzi-Flores, Norberto Farfán, Abdelhamid Ben Salah, Carme Nogués*, and Rosario Núñez*. Bioconjugate Chemistry. DOI: 10.1021/acs.bioconjchem.8b00204
A series of novel fluorescent BODIPY-anionic boron cluster conjugates bearing [B12H12]2– (5, 6), [3,3′-Co(1,2-C2B9H11)2]− (7, 8), and [3,3′-Fe(1,2-C2B9H11)2]− (9) anions have been readily synthesized from meso-(4-hydroxyphenyl)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY 4), and their structure and photoluminescence properties have been assessed. Linking anionic boron clusters to the BODIPY (4) does not alter significantly the luminescent properties of the final fluorophores, showing all of them similar emission fluorescent quantum yields (3–6%). Moreover, the cytotoxicity and cellular uptake of compounds 5–9 have been analyzed in vitro at different concentrations of B (5, 50, and 100 μg B/mL) using HeLa cells. At the lowest concentration, none of the compounds shows cytotoxicity and they are successfully internalized by the cells, especially compounds 7 and 8, which exhibit a strong cytoplasmic stain indicating an excellent internalization efficiency. To the best of our knowledge, these are the first BODIPY-anionic boron cluster conjugates developed as fluorescent dyes aiming at prospective biomedical applications. Furthermore, the cellular permeability of the starting BODIPY (4) was improved after the functionalization with boron clusters. The exceptional cellular uptake and intracellular boron release, together with the fluorescent and biocompatibility properties, make compounds 7 and 8good candidates for in vitro cell tracking.