Monomer Versus Dimer of Cationic Ir(III) Complexes for Photodynamic Therapy by Two-Photon Activation: A Comparative Study

Iridium(III) complexes have been recognized as promising candidates for two-photon sensitized photodynamic therapy (PDT). In this context, we report on the study of two complexes: a monomer (<b>IrL</b>^<b>1</b>) and a dimer (<b>Ir</b>_<b>2</b><b>L</b>^<b>2</b>). Both complexes possess 2-phenylpyridine cyclometallating ligands and a pyridylbenzimidazole derivative as an ancillary ligand. In the dimer, the two Ir(III) centers are connected by a non-conjugated bridged bis(pyridylbenzimidazole). We compare the photophysical properties of these complexes. Both display phosphorescent emission in the orange-red part of the visible spectrum, with emissions centered at 610 nm for <b>IrL</b>^<b>1</b> and 625 nm for <b>Ir</b>_<b>2</b><b>L</b>^<b>2</b>, both exhibiting quantum yields of ∼24%. However, <b>Ir</b>_<b>2</b><b>L</b>^<b>2</b> proves to be much brighter than the monomer, making the dimer four times brighter than <b>IrL</b>^<b>1</b>. This trend is consistent under two-photon excitation (TPE), and the singlet oxygen generation quantum yields, with the dimer displaying a figure of merit (σ_TPA × Φ_Δ) of 40, compared to only 5 for the monomer. Both complexes generate intracellular ROS and exhibit strong phototoxicity upon blue light activation (λ = 420 nm), achieving submicromolar IC₅₀ values in HT29 and A549 cell lines after 24 h of incubation. Moreover, with TPE (λ = 800 nm), both complexes also generate intracellular ROS and induce cancer cell death.