Autor(es):
Gonzalo-Navarro, Carlos ; Zafon, Elisenda ; Organero, Juan Angel ; Jalón, Félix A. ; Lima, João Carlos ; Espino, Gustavo ; Rodríguez, Ana María ; Santos, Lucía ; Moro, Artur J. ; Barrabés, Sílvia ; Castro, Jessica ; Camacho-Aguayo, Javier ; Massaguer, Anna ; Manzano, Blanca R. ; Durá, Gema
Data: 2024
Identificador Persistente: http://hdl.handle.net/10362/166750
Origem: Repositório Institucional da UNL
Projeto/bolsa:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT;
Assunto(s): Molecular Medicine; Drug Discovery; SDG 3 - Good Health and Well-being
Descrição
This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (PID2021-127187OB-C21, PID2021-127187OB-C22), PID2019-105408GB-I00, Junta de Comunidades de Castilla-La Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260), Junta de Castilla y León (BU087G19), and UCLM-FEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). C.G. acknowledges his fellowship to both the European Social Fund and Plan Propio de I+D+I of UCLM (2022-PRED-20649). G.D. thanks the Junta de Comunidades de Castilla la Mancha and EU for financial support through the European Regional Development Fund (project SBPLY/19/180501/000191). Dr. F. Javier Galbán, head of the group “Analytical Biosensors Group” of Zaragoza University is also acknowledged. Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.
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.
