Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Carlos Gonzalo-Navarro, Elisenda Zafon, Juan Angel Organero, Félix A. Jalón, João Carlos Lima, Gustavo Espino, Ana María Rodríguez, Lucía Santos, Artur J. Moro, Sílvia Barrabés, Jessica Castro, Javier Camacho-Aguayo, Anna Massaguer, Blanca R. Manzano, Gema Durá

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
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Abstract

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT.
Original languageEnglish
Pages (from-to)1783-1811
Number of pages29
JournalJournal Of Medicinal Chemistry
Volume67
Issue number3
Early online date31 Jan 2024
DOIs
Publication statusPublished - 8 Feb 2024

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