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

Abstract

Bioactive and luminescent cyclometallated Ir(III) complexes [Ir(ppy) 2 L1]Cl (1) and [Ir(ppy) 2 L2]Cl (2) containing a benzimidazole derivative (L1/L2) as auxiliary mimic of a nucleotide have been synthesised. The emissive properties of both complexes are conditioned by the nature of L1 and L2, rendering an orange and a green emitter respectively. Both are highly emissive with quantum yield increasing in absence of oxygen up to 0.26 (1) and 0.36 (2), suggesting their phosphorescent character. Antiproliferative activity against lung cancer A549 cells increased up to 15 times upon irradiation conditions, reaching IC 50 values in the nanomolar range (0.3 � 0.09 μM (1) and 0.26 � 0.14 μM (2)) and pointing them as good PSs candidates for photodynamic therapy via 1 O 2 generation. Cellular biodistribution analysis by fluorescence microscopy suggest the lysosomes as the preferential accumulation organelle. Time-resolved studies showed a greatly increased cellular emission lifetime compared to the solution values, indicating binding to macromolecules or cellular structures and restriction of collision and vibrational quenching.

Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells

“…The broad bands at 350–430 nm could be attributed to the metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT) transition. In contrast, the weak absorption shoulders at ∼450 nm are considered spin-forbidden 3 MLCT/LLCT transition as a consequence of the spin–orbit coupling of an Ir­(III) heavy atom (ζ = 3909 cm –1 ), which allows for fast and efficient intersystem crossing (ISC) to convert singlet excitons to triplets. ,− The triplet nature of these excited states could make them appropriate for bioimaging and photodynamic therapy . As observed, subtle structural modifications of the C^N ligand only moderately affected the UV/Vis absorption spectra of the corresponding Ir­(III) complexes in both acetonitrile and water.…”

Current status of iridium-based complexes against lung cancer

“…Another compound 39 can induce apoptosis of lung cancer cells by activating PI3K-Akt-mTOR and endoplasmic reticulum stress pathway, and inhibit migration of lung cancer cells by blocking mitotic process (Table 1). Recently, Redrado and co-workers synthesized a cyclometallated iridium (III) complex 40 (Figure 4) with biological activity and luminescent properties using benzimidazole derivatives as ligands, which can target lysosomes (Redrado et al, 2022).…”

Rhenium fac-Tricarbonyl Bisimine Chalcogenide Complexes: Synthesis, Photophysical Studies, and Confocal and Time-Resolved Cell Microscopy

“…While there are many reports of the application of these complexes in biological imaging, and of their long lifetimes, there are relatively few reports of the application of such complexes in time-resolved imaging studies, − while iridium and ruthenium complexes, for example, are commonly used in this way. − Time-resolved microscopy with triplet emitters takes advantage of their long lifetimes in a variety of different ways, principally time gating or lifetime mapping. Time-gated techniques differentiate between short-lived emission from singlet emitters such as autofluorescence or organic fluorophores by separating the long-lived components of a decay from the shorter components and generating images consisting solely of the light emitted after a given time period, illustrating the distribution of the metal complexes. , Lifetime mapping generates a single image containing all of the decay components but with each pixel colored on a lifetime scale rather than by intensity or wavelength of emission, giving an image that visually presents differences in excited-state lifetime across the cells.…”