Phosphorescent Iridium(III) Complexes for Anticancer Applications

Abstract

Great attention has been bestowed upon iridium(III) complexes as anticancer agents in recent years, and a variety of them, in particular, are luminescent. The phosphorescence of these compounds facilitates the visualization and monitoring of their subcellular localization and interactions with other molecules or structures during anticancer therapy, which might help demonstrate the inner pathways and molecular mechanisms of the complexes. In this review, we focus on the development of phosphorescent iridium(III) complexes for anticancer applications in recent five years and intend to highlight some newly reported Ir(III) complexes that are targeting specific organelles, inducing different cell death modes, or photoactivated agents in phototherapies including photodynamic therapy and photoredox catalysis.

Induction of Paraptosis by Cyclometalated Iridium Complex-Peptide Hybrids and CGP37157 via a Mitochondrial Ca2+Overload Triggered by Membrane Fusion between Mitochondria and the Endoplasmic Reticulum

“…Cyclometalated iridium (Ir) complexes such as fac -Ir­(tpy) 3 1a [tpy = 2-(4′-tolyl)­pyridine] and fac -Ir­(ppy) 3 1b (ppy = 2-phenylpyridine) have high photophysical properties that include long Stokes shifts, high quantum yields, and long emission lifetimes. − Therefore, Ir complexes have been proposed as attractive candidates as phosphorescent materials such as in organic light-emitting diodes (OLEDs), , photoredox catalysts, , bioimaging probes, − anticancer agents, , and related tools. We previously reported Ir complex-peptide hybrids (IPHs) that possess H 2 N-KK­(K)­GG peptide sequences (K, lysine; G, glycine) at the 5′- or 4′-position (the para or meta position with respect to the C–Ir bond) of the ligands, 2 and 3 or 4 , respectively (Chart ).…”

Photoactive and Luminescent Transition Metal Complexes as Anticancer Agents: A Guiding Light in the Search for New and Improved Cancer Treatments

“…Mitochondrial targeting has been achieved by a variety of complexes with both simple and complex structures; it is thought that the intrinsic nature of iridium complexes results in mitochondrial targeting [17]. These complexes typically induce cytotoxicity by reactive oxygen species (ROS) production within mitochondria, triggering apoptosis.…”

“…Unlike mitochondrial targeting, lysosomal targeting is not intrinsic to most iridium(III) complexes. Although most "half-sandwich/piano stool" complexes have been reported to target lysosomes [17], ligand modification within families of complexes can result in both mitochondrial and lysosomal targeting [21,24,[30][31][32]. Other recent examples include complexes that incorporate imine-N-heterocyclic carbine, which has shown localization in the lysosome using fluorescent co-localization studies and exhibited very good IC 50 values (Table 1:IR13) [33].…”

Tunable Emissive Ir(III) Benzimidazole‐quinoline Hybrids as Promising Theranostic Lead Compounds

“…Initially, cyclometallated Ir(III) complexes were proposed as alternative cellular markers to organic fluorophores, [10] due to their rich photophysical properties. However, the specific biological behaviour shown by many of them in terms of biological sensing and therapy, has opened the scope of the investigations to these new areas [11] …”

“…However, the specific biological behaviour shown by many of them in terms of biological sensing and therapy, has opened the scope of the investigations to these new areas. [11] Regarding cellular visualisation, fluorescence microscopy and, more recently, Fluorescence Lifetime Imaging (or Mapping) known as FLIM are techniques widely used to monitor localisation or response to stimuli at the sub-cellular level, [12] relaying on the emission and excited state lifetimes of the markers respectively. In this sense, d-block metal phosphorescent probes, and in particular, iridium based complexes possess excellent photophysical properties for both techniques.…”