Game of ligands: tuning the photodynamic activity of P(<scp>v</scp>) porphyrins in aqueous media

For developing novel photosensitizers (PS), three series of phosphorus(V) tetra-<i>meso</i>-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.