Synthesis of asymmetric cationic zinc porphyrin photosensitizer containing thiophene group for photodynamic therapy in vitro and theoretical calculation of DFT

• Published in: Journal of molecular structure 2024-04, Vol.1302, p.137497, Article 137497
• Main Authors: Zhang, Wen-Yuan, Li, Gui-Chen, Wang, Bo, Fan, Yan, Sun, Xue-Qin, Yang, Yi-Xin, Zhang, Chun-Yan, Feng, Xiao-Xia, Xu, Wei-Bing, Liu, Jia-Cheng
• Format: Article
• Language: English
• Subjects: Photodynamic therapy; Photosensitizer; Porphyrin; ROS
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.137497

•Three types of thiophene zinc porphyrin photosensitizers (Zn-P1, Zn-P2, and Zn-P3) with varied side chains were synthesized using adept methods. The issue of poor water solubility of porphyrin photosensitizers was resolved through a methylation reaction.•Based on density functional theory and singlet oxygen production experiments, Zn-P1 exhibited the utmost activity and remarkable singlet oxygen production capabilities.•The Zn-P1 demonstrated notable phototoxicity and selectivity towards HepG2 cells according to the cytotoxicity test. The anti-cancer mechanism was explained by cell staining experiment and reactive oxygen species experiment. The photosensitizer produces reactive oxygen species when exposed to light, inducing apoptosis in cancer cells. Porphyrins, as photosensitizers for photodynamic therapy, is used to treat various cancers. In this study, three different side-chain variants of thiophene-zinc porphyrins were synthesized (Zn-P1, Zn-P2, and Zn-P3). Among the synthesized compounds, Zn-P1 exhibited the highest activity and demonstrated superior singlet oxygen generation capability according to both density functional theory calculations and singlet oxygen generation experiments. Our cytotoxicity assays revealed that Zn-P1 exhibited remarkable phototoxicity along with a pronounced selectivity for HepG2 cells. This selectivity was confirmed by cell staining experiments, which showed obvious apoptotic processes. Further insight into this anticancer mechanism was provided by cell reactive oxygen species experiments, which explained the induction of cancer cell apoptosis. Light-activated production of reactive oxygen species by photosensitizers initiates the apoptotic cascade in cancer cells. This study highlights the utility of cationic porphyrin photosensitizer complexes in photodynamic therapy and provides new insights for the development of innovative photosensitizers in cancer treatment.