TY - JOUR
T1 - Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy
AU - Gonzalo-Navarro, Carlos
AU - Zafon, Elisenda
AU - Organero, Juan Angel
AU - Jalón, Félix A.
AU - Lima, João Carlos
AU - Espino, Gustavo
AU - Rodríguez, Ana María
AU - Santos, Lucía
AU - Moro, Artur J.
AU - Barrabés, Sílvia
AU - Castro, Jessica
AU - Camacho-Aguayo, Javier
AU - Massaguer, Anna
AU - Manzano, Blanca R.
AU - Durá, Gema
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT#
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.
PY - 2024/2/8
Y1 - 2024/2/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85184663421&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.3c01276
DO - 10.1021/acs.jmedchem.3c01276
M3 - Article
C2 - 38291666
AN - SCOPUS:85184663421
SN - 0022-2623
VL - 67
SP - 1783
EP - 1811
JO - Journal Of Medicinal Chemistry
JF - Journal Of Medicinal Chemistry
IS - 3
ER -