التفاصيل البيبلوغرافية
| العنوان: |
Towards efficient Ir(III) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands. |
| المؤلفون: |
Sanz-Villafruela, Juan, Bermejo-Casadesús, Cristina, Martínez-Alonso, Marta, Moro, Artur, Lima, João C., Massaguer, Anna, Espino, Gustavo |
| المصدر: |
Dalton Transactions: An International Journal of Inorganic Chemistry; 7/21/2024, Vol. 53 Issue 27, p11393-11409, 17p |
| مستخلص: |
In this work we disclose a new family of biscyclometallated Ir(III) complexes of the general formula [Ir(C^N)2(N^N)]Cl (IrL1–IrL5), where HC^N is 1-phenyl-β-carboline and N^N ligands (L1–L5) are different diimine ligands that differ from each other in the number of aromatic rings fused to the bipyridine scaffold. The photophysical properties of IrL1–IrL5 were thoroughly studied, and theoretical calculations were performed for a deeper comprehension of the respective variations along the series. All complexes exhibited high photostability under blue light irradiation. An increase in the number of aromatic rings led to a reduction in the HOMO–LUMO band gap causing a red-shift in the absorbance bands. Although all the complexes generated singlet oxygen (1O2) in aerated aqueous solutions through a photocatalytic process, IrL5 was by far the most efficient photosensitizer. Consequently, IrL5 was highly active in the photocatalytic oxidation of NADH. The formation of aggregates in DMSO at a high concentration (25 mM) was confirmed using different techniques, but was proved to be negligible in the concentration range of biological experiments. Moreover, ICP-MS studies proved that the cellular uptake of IrL2 and IrL3 is much better relative to that of IrL1, IrL4 and IrL5. The antiproliferative activity of IrL1–IrL5 was investigated in the dark and under blue light irradiation against different cancer cell lines. Complexes IrL1–IrL4 were found to be cytotoxic under dark conditions, while IrL5 turned out to be weakly cytotoxic. Despite the low cellular uptake of IrL5, this derivative exhibited a high increase of cytotoxicity upon blue light irradiation resulting in photocytotoxicity indexes (PI) up to 38. IrL1–IrL4 showed lower photocytotoxicity indexes ranging from 1.3 to 17.0. Haemolytic experiments corroborated the compatibility of our complexes with red blood cells. Confocal microscopy studies proved their accumulation in mitochondria, leading to mitochondrial membrane depolarization, and ruled out their localization in lysosomes. Overall, the mitochondria-targeted activity of IrL5, which inhibits considerably the viability of cancer cells upon blue light irradiation, allows us to outline this PS as a new alternative to traditional chemotherapeutic agents. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
