Synthesis, Photophysical Properties, and Photodynamic Therapy Efficacies of Meso-Pyridine Bodipys and Their Ruthenium Complexes

Abstract

Photodynamic therapy (PDT) is a candidate approach for cancer treatment. In PDT applications, a fluorescent molecule, called photosensitizer (PS), induces light-directed production of reactive species, resulting in cytotoxicity. Having tunable fluorescence and easy derivatization properties, the BODIPY core is widely used as a PS. To further increase the light-induced toxicity, studies have shown the conjugation of heavy metals to the BODIPY core. However, such complexes are still needed to fully figure out their potential. In the current study, as part of an ongoing one, two novel ruthenium-BODIPY complexes were synthesized and characterized by structural, photophysical, and biological methods. To obtain complex structures between ruthenium dimers and BODIPY units, [RuCl2(p-cymene)](2) dimers, and non-iodo and di-iodo BODIPY derivatives were reacted in methanol-tetrahydrofuran (THF) medium. Photophysical properties, fluorescence lifetime, molar extinction coefficient, photostability, and capability of singlet oxygen generation were determined using absorption and/or fluorescence spectroscopy. Besides, the structures of the complexes were further clarified by the single-crystal X-ray technique. The cytotoxicity of compounds was examined against the human cervical cancer cell line, HeLa, and breast cancer cell line, MDA-MB-231, both in the dark and by light irradiation. Accordingly, both precursors and their ruthenium complexes were light-dependent toxic; nevertheless, di-iodinated meso-pyridine-substituted BODIPYs displayed light-independent toxicity by long-term treatments. Moreover, the effects of the complexes were cell-specific and the toxicities of di-iodinated BODIPY complexes were inversely correlated with the concentrations, underlying a possible aggregation and/or unpredicted cellular interaction pattern. These results emphasize that further functionalization and molecular characterization of BODIPY-ruthenium complexes are still required for PDT applications.