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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 54; no. 24; pp. 9553 - 9564
• Main Authors: Efimova, Inessa A, Safonova, Evgeniya A, Polovkova, Marina A, Gorshkov, Egor V, Egorova, Tatiana V, Akasov, Roman A, Tsivadze, Aslan Yu, Gorbunova, Yulia G
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 17.06.2025
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aqueous solutions; Bioaccumulation; Cancer; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Cytotoxicity; Drug Screening Assays, Antitumor; Fluorescence; Humans; Ligands; MCF-7 Cells; Molecular Structure; Organelles; Phosphorus - chemistry; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Porphyrins; Porphyrins - chemistry; Porphyrins - pharmacology; Singlet oxygen; Singlet Oxygen - chemistry; Singlet Oxygen - metabolism; Substitutes; Toxicity; Water - chemistry
• ISSN: 1477-9226; 1477-9234; 1477-9234
• DOI: 10.1039/d5dt00808e

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 IC 50 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 (IC 50 = 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. In this work, the tendencies of photostability, light cytotoxicity, accumulation in cells and the ability to undergo dephosphorylation depending on the structure of P( v ) porphyrins are demonstrated.