Multifunctional Heterometallic Ir<sup>III</sup>−Au<sup>I</sup> Probes as Promising Anticancer and Antiangiogenic Agents
Marta Redrado, Andrea Benedi, Isabel Marzo, A.L. García-Otín, Vanesa Fernández‐Moreira, M. Concepción Gimeno
Abstract
Abstract A new class of emissive cyclometallated Ir III −Au I complexes with a bis(diphenylphosphino) methanide bridging ligand was successfully synthesised from the diphosphino complex [Ir(N^C) 2 (dppm)] + ( 1 ). The different gold ancillary ligand, a triphenylphosphine ( 2 ), a chloride ( 3 ) or a thiocytosine ( 4 ) did not reveal any significant effect on the photophysical properties, which are mainly due to metal‐to‐ligand charge‐transfer ( 3 MLCT) transitions based on Ir III . However, the Au I fragment, along with the ancillary ligand, seemed crucial for the bioactivity in A549 lung carcinoma cells versus endothelial cells. Both cell types display variable sensitivities to the complexes (IC 50 =0.6–3.5 μM). The apoptotic pathway is activated in all cases, and paraptotic cell death seems to take place at initial stages in A549 cells. Species 2 – 4 showed at least dual lysosomal and mitochondrial biodistribution in A549 cells, with an initial lysosomal localisation and a possible trafficking process between both organelles with time. The bimetallic Ir III −Au I complexes disrupted the mitochondrial transmembrane potential in A549 cells and increased reactive oxygen species (ROS) generation and thioredoxin reductase (TrxR) inhibition in comparison with that displayed by the monometallic complex 1 . Angiogenic activity assays performed in endothelial cells revealed the promising antimetastatic potential of 1 , 2 and 4 .