Game of ligands: tuning the photodynamic activity of P(v) porphyrins in aqueous media†

Abstract

For developing novel photosensitizers (PS), three series of phosphorus(V) tetra-meso-aryl-substituted porphyrins, bearing varying numbers of pyridyl groups (0 to 2) and different axial ligands (–OH, –OEt, –OPrOH) are obtained. All complexes exhibit fluorescence in EtOH with moderate quantum yields (0.10–0.15) and singlet oxygen (SO) generation with high quantum yields (0.58–0.87). Photostability, fluorescence, and SO generation quantum yields increase with a reduction in the number of pyridyl groups. Moreover, using P(V) mono-pyridyl-substituted porphyrins as an example, it was demonstrated that photostability and SO generation depend on the nature of the axial ligands, with an increase observed in the following series: –OH < –OPrOH < –OEt. Interestingly, P(V) porphyrins with axial –OH ligands are subject to intracellular dephosphorylation and accumulation in human carcinoma cell organelles (apparently in lysosomes), whereas complexes with axial –OEt groups remain in the initial state and are diffusely distributed throughout the cytoplasm. Remarkably, P(V) complexes exhibit high photoinduced cytotoxicity against human breast adenocarcinoma MCF-7 and human lung adenocarcinoma A-549 cells, with IC₅₀ values reaching the nanomolar range. Mono-pyridyl-three-phenyl and tetraphenyl complexes bearing –OEt axial ligands are the most promising photosensitizing agents, with the highest light cytotoxicity (IC₅₀ = 2.0 and 5.7 M for A-549 and 8.9 and 14 nM for MCF-7 cells, respectively). The dose-dependent effect has also been demonstrated, confirming a light-induced mechanism of cell death.