Brominated BODIPYs as potential photosensitizers for photodynamic therapy using a low irradiance excitation

Abstract

Three novel BODIPY-chromophores 4, 6 and 7 were synthesized by simple condensation reaction of thiocarboxaldehyde and pyrrole ring. Molecular structures were designed to contain thiophene rings and different arrangements for bromine substitution. The effect of these arrangements on the generation of singlet oxygen and optical properties was studied. In general, the presence of thiophene rings produces red-shifts in absorption spectra while three bromine substitution (6) tend to produce the largest singlet oxygen generation. Results show that these BODIPYs are excellent chromophores with high absorption coefficient, however they are poor fluorophores (with quantum yields <1%). Compounds 4, 6 and 7 were evaluated in three different organic solvents for the generation of singlet oxygen by using a spectrophotometric method, obtaining maximum quantum efficiencies of singlet oxygen generation of 84, 93 and 74% for 4, 6 and 7, respectively. The compounds comprise excellent photo- and chemical stability against reactive oxygen species. These BODIPYs show good compatibility to aqueous media and conserve most of their optical properties obtained in organic solvents. These results motivated to evaluate these BODIPYs as photosensitizers in photodynamic therapy (PDT). In particular, 4 used as photosensitizer showed 60% of HeLa cells viability reduction, determined by MTT assay.