Synthesis, Spectroscopic, Computational, and PDT Investigations of a Series of Cationic Meso -(3-pyridyl)-indolylstyryl-BODIPYs

Boron dipyrromethene (BODIPY) dyes bearing a meso-(3-pyridyl) moiety have found multiple applications, such as pH and metal ion sensors, fluorescence probes, and as sensitizers for phototherapy. A series of 3-mono- and 3,5-di-indolylstyryl-BODIPYs bearing a meso-(3-pyridyl) group and different 2,6-substituents (H, Cl, Br, I) was synthesized and their properties investigated. The extension of π-conjugation via the indolylstyryl groups produced bathochromic shifts in the absorption and emission spectra of up to 200 nm, while the introduction of the heavy 2,6-iodo groups induced the highest in vitro and in vivo phototoxicity. In a comparison study with Photofrin, mono-indolylstyryl-BODIPY 4a cat was found to be a potent photosensitizer (IC50 = 11 μM at 3 J/cm2; under the same conditions Photofrin’s IC50 = 24 μM) in HT-29 cells. In mice bearing HT-29 xenograft tumors, BODIPY 4a cat shows similar PDT efficacy as Photofrin and is the most promising photosensitizer among the new series of meso-(3-pyridyl)-BODIPYs.