Ir Complexes Research Articles

(2,9-Dimethyl-1,10-phenanthroline)bis[2-(pyridin-2-yl)phenyl]iridium(III) hexafluorophosphate and (2,9-dimethyl-1,10-phenanthroline)bis[5-methyl-2-(pyridin-2-yl)phenyl]iridium(III) hexafluorophosphate–diethyl ether–acetonitrile (1/0.61/0.78)

The title compounds, [Ir(C14H12N2)(C11H8N)2]PF6 (1) and [Ir(C14H12N2)(C12H10N)2]PF6·0.61C2H10O·0.78CH3CN (2), crystallize in the space groups Pbca and P 1, respectively, each structure containing one monocationic Ir complex and one PF6 − anion in the asymmetric unit. The anion and solvent in compound 2 are disordered. The Ir—N(phenanthroline) bond lengths of ca. 2.21 Å indicate a greater steric effect of the 2,9-dimethyl-1,10-phenanthroline ligand compared to 1,10-phenanthroline. Both structures show offset parallel intermolecular π–π interactions between the pyridine rings of the phenanthroline ligands, and that of 1 also exhibits similar interactions between the phenyl and pyridine rings of the phenylpyridine ligands.

AIPE-Active Neutral Ir(III) Complexes as Bi-Responsive Luminescent Chemosensors for Sensing Picric Acid and Fe3+ in Aqueous Media

AIPE-Active Neutral Ir(III) Complexes as Bi-Responsive Luminescent Chemosensors for Sensing Picric Acid and Fe3+ in Aqueous Media

Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer.

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT and PTT) for cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen and superoxide anion, and release heat when exposed to infrared (IR) irradiation, thus inducing reactive oxygen species (ROS)-associated cell disruption and thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis. Additionally, the ROS deplete intracellular glutathione, lead to lipid peroxidation, and induce ferroptosis. The selected dinuclear Ir(III) complex Ir4 can completely eradicate cisplatin-resistant non-small-cell lung tumor in 75% of the phototreated mice with an inhibition rate of tumor growth above 96%. They have an extremely low toxicity to normal liver and kidney cells. After therapy, metal was not detected in the collected organs of mice except the tumor. A synergistic therapy consisting of potent IR-driven PDT and mild PTT accomplished by single-molecule dinuclear Ir(III) complexes is highly significant for the safe and effective PDT of large, deep-seated tumors as well as for overcoming the complicated drug resistance mechanisms of cancer.

Dual-linker Ir-Zr-MOF shows improved porosity to enhance aqueous sulfide photooxidation.

The hetero photooxidation of sulfide under aqueous conditions is of great importance in the green synthesis of sulfoxide. This process requires a type of solid photocatalyst with the properties of high porosity and water stability, as well as photosensitivity. Herein, a stable Ir-Zr-MOF material (compound 1) with high porosity is assembled from two linear linkers of a 2-phenylquinoline-4-carboxylic acid-Ir(III) complex (Irphen) and 4,4'-stilbenedicarboxylic acid (H2SDC), and a Zr6 cluster. 1 is isostructural to JLU-Liu34 with a composition of [Zr6O4.78(OH)3.22(SDC)3.82(Irphen)0.78TFA2.8]·2.8MeOH and permanent porosity with a BET surface area of 1507 m2 g-1. 1 exhibits improved activity for the photocatalytic aerobic oxidation of sulfide to sulfoxide via blue light irradiation under aqueous conditions. Mechanism studies demonstrate that a superoxide radical is the reactive oxygen species in the sulfide photooxidation. 1 can be readily recycled and reused at least 5 times without loss of catalytic activity. This work not only provides a good strategy for the assembly of an Ir(III) complex into MOFs but also an efficient method for the green synthesis of sulfoxide.

Breaking the deep-red light absorption barrier of iridium(III)-based photosensitizers.

Activating photosensitizers with long-wavelength excitation is an important parameter for effective photodynamic therapy due to the minimal toxicity of this light, its superior tissue penetration, and excellent spatial resolution. Unfortunately, most Ir(III) complexes suffer from limited absorption within the phototherapeutic window, rendering them ineffective against deep-seated and/or large tumors, which poses a significant barrier to their clinical application. To address this issue, several efforts have been recently made to shift the absorption of Ir(III) photosensitizers to the deep-red/near-infrared region by using different strategies: functionalization with organic fluorophores, including porphyrinoid compounds, and ligand design via π-extension and donor-acceptor interactions. In this Frontier, we highlight such new developments and the ongoing challenges in this field.

Click-ready iridium(iii) complexes as versatile bioimaging probes for bioorthogonal metabolic labeling.

Herein, we report the synthesis, photophysical characterization and validation of iridium(iii)-polypyridine complexes functionalized for click chemistry and bioorthogonal chemistry, as well as their versatile applications as probes in bioimaging studies exploiting metabolic labeling. The designed dyes are conjugated to chemical reporters in a specific manner within cells by CuAAC ligation and display attractive photophysical properties in the UV-visible range. They are indeed highly photostable and emit in the far-red to near-IR region with long lifetimes and large Stokes shifts. We demonstrate that they can be efficiently used to monitor nascent intracellular sialylated glycoconjugates in bioorthogonal MOE studies with a varied panel of optical and non-optical techniques, namely conventional UV-vis laser scanning confocal microscopy (for routine purposes), UV-vis time-resolved luminescence imaging (for specificity and facilitated multiplexing with nano-environment sensitivity), synchrotron radiation based X-ray fluorescence nanoimaging (for high resolution, elemental mapping and quantification in situ) and inductively coupled plasma mass spectrometry (for routine quantification on cell populations with high statistical confidence). The synthesized Ir(iii) complexes were utilized in single labeling experiments, as well as in dual click-labeling experiments utilizing two distinct monosaccharide reporters relevant to the same metabolic pathway.

Selective electroreduction of CO2 to formate by a heterogenized Ir complex using H2O as an electron/hydrogen source

A new PNNP-coordinated iridium complex, Mes-IrPPh2, immobilized on carbon was a superior catalyst for the CO2 electrochemical reduction in water to give formate, allowing the solar-to-chemical conversion efficiency of 13.7%.

Phosphorescent Sensor Based on Iridium(III) Complex with Aggregation-Induced Emission Activity for Facile Detection of Volatile Acids.

Phosphorescent sensors are essential for rapid visual sensing of volatile acids, due to their profound impact on ecosystems and human health. However, solid phosphorescent materials for acid-base stimulus response are still rare, and it is important to achieve real-time monitoring of volatile acids. In order to obtain an efficient and rapid response to volatile acid stimulation, N-H and -NH2 substituents are introduced into an auxiliary ligand to synthesize a new cationic Ir(III) complex (Ir-NH). The AIE property of Ir-NH leads to enhanced emission in the aggregated state, which facilitates the construction of solid-state acid-base sensors. More importantly, due to the introduction of -NH2 and N-H in the molecular structure, reversible switching of the emission color of Ir-NH under acid-base stimulation was successfully achieved. A convenient and efficient sensing device for volatile acid monitoring was prepared using Ir-NH as the active material. Our results provide a new strategy for designing phosphorescent materials with AIE and acid-base stimulus-responsive properties.

Synthesis and luminescence of 3-(pyridine-2-yl)-1,2,4-triazine-based Ir(III) complexes

A series of novel iridium(III) complexes containing 5-N-(aryl)-amino- or 5-cycloamino-3-(pyridine-2-yl)-1,2,4-triazine ligands was obtained. These complexes exhibited red luminescence in solution as well as in the solid state. Based on the DFT studies it was suggested that N(2) atom of the 1,2,4-triazine core is preferable to N(4) one as the coordination site in the complexes of Ir(III).

Discovery of Novel Iridium(III) Complex‐Based Photofunctional Materials Using Excited‐State Descriptors

AbstractThe design of iridium(III) complex‐based photofunctional materials is challenged by commercial viability issues in organic light‐emitting diodes (OLEDs) and the limitation of polypyridyl structures for Ir(III) catalysts in photocatalysis. The burgeoning advancement of data‐driven science provides new solutions to this challenge. Herein, a three‐step data‐driven design approach is reported to target multifunctional red phosphorescent Ir(III) complexes. The approach uses machine learning and quantum chemistry calculations coupled with key excited‐state physical and chemical descriptors to identify the promising natural uracil‐based Ir(III) complexes from the self‐established “OLED Materials and Photocatalyst Database.” The newly designed red complexes demonstrate higher quantum yields and longer radiative lifetimes compared to their commercial counterparts. As photosensitizers, they display electron and energy transfer rates with substrates at the nanosecond level and are validated for lab‐scale photocatalysis. As the guests for OLEDs, their devices produce excellent red emission with low turn‐on voltages, minimal efficiency roll‐off, and decent electroluminescence efficiency. This research stands for an innovative endeavor in the data‐driven design of Ir(III) complexes, diverging from the traditional structure‐mimicking model, and can be generalized to the design of more photofunctional molecular materials.

Iridium Complexes of a Bis(N-pyrrolyl)boryl/Bis(phosphine) PBP Pincer Ligand.

This work reports the synthesis of a bis(pyrrolylphosphino)phenyl borane (PBP)Ph (2) and its incorporation of Ir by metal insertion into B-Ph to afford the dipyrrolylboryl/bis(phosphine) pincer complex (PBP)Ir(Ph)Cl (3). Hydrogenolysis of 3 afforded (PBP)Ir(H)Cl (4). Compound 4 was converted into (PBP)IrCl2 (5a) via reaction with N-chlorosuccinimide, and exposure of 5a to CO produced (PBP)IrCl2(CO) (6a). Compounds 5a and 6a were converted into their analogs (PBP)IrI2 (5b) and (PBP)IrI2(CO) (6b) via metathesis with Me3SiI, respectively. Treatment of either 3 or 4 with Li[HAl(OtBu)3] under H2 resulted in the formation of (PBP)IrH4 (7), with traces of 4 as a persistent impurity. Attempts to access 7 via the reaction of 4 with NaBH4 in isopropanol led to the loss of boron from the pincer and isolation of L2IrH5 (8, L = 2-diisopropylphosphinopyrrole). Compounds 4, 7, and 8 were examined as catalysts for alkane transfer dehydrogenation but displayed only the modest activity. Solid-state structures of 6b and 7 were established by X-ray crystallography.

Disulfide-Bridged Cationic Dinuclear Ir(III) Complex with Aggregation-Induced Emission and Glutathione-Consumption Properties for Elevating Photodynamic Therapy.

The ability of photosensitizers (PSs) to generate reactive oxygen species (ROS) is crucial for photodynamic therapy (PDT). However, many traditional PSs face the drawbacks that aggregation-caused quenching (ACQ) and highly expressed glutathione (GSH) in the tumor microenvironment seriously limit their ROS generation ability. Herein, we report two cationic dinuclear iridium complexes, Ir-C-C-Ir and Ir-S-S-Ir, which possess aggregation-induced emission (AIE). Ir-S-S-Ir was constructed for GSH consumption by introducing a disulfide linkage between the two auxiliary ligands with imine units. Quantum chemical calculations revealed that Ir-C-C-Ir and Ir-S-S-Ir possess many degenerate states, which provide more channels for singlet-to-triplet exciton transitions, and then the intersystem crossing rate is increased due to the heavy atom effect of the iridium and sulfur atoms. The ROS production experiments indicated that the singlet oxygen yield of Ir-S-S-Ir was 33 times more than that of the ACQ mononuclear iridium complex Ir-C. Most importantly, Ir-S-S-Ir consumed GSH through a thiol-disulfide exchange reaction, as demonstrated by mass spectrometry and high-performance liquid chromatography. Cell experiments testified that Ir-S-S-Ir consumes GSH in tumor cells, possesses good ROS production capacity, and exhibits an extraordinary PDT effect. This is the first report of an AIE dinuclear iridium complex with a GSH-consuming function.

Increased phosphorescence of cyclometalated Ir(III) complex with a planar triarylborane moiety upon fluoride anion binding

Abstract A luminescent Ir(III) complex functionalized with a planar triarylborane moiety was prepared. This complex exhibits unique photophysical properties derived from the electron-withdrawing effect of the triarylborane moiety. A significant change in electron density occurs upon binding of F– to the electron-deficient boron center, resulting in decreased absorption and enhanced emission.

Endocytic Uptake of Self-Assembled Iridium(III) Nanoaggregates for Holistic Treatment of Metastatic 3D Triple-Negative Breast Tumor Spheroids.

Triple-negative breast cancer (TNBC) presents a formidable challenge due to its aggressive behavior andlimited array of treatment options available. This study focuses on employing nanoaggregate material of organometallic Ir(III) complexes for treatingTNBC cell line MDA-MB-231. In this approach, Ir(III) complexes with enhanced cellular permeability are strategically designed and achieved through the incorporation of COOMe groups into their structure. The lead compound, IrL1, exhibits promiscuous nanoscale aggregation in RPMI cell culture media, characterized by a stable hydrodynamic effective diameter ranging from 190 to 202 nm over 48 h.With excellent photo-responsive contrast-enhanced cell imaging properties IrL1 exhibits an outstanding IC50, 48hvalue of 36.05± 0.03 nm when irradiated with 390 nm light in MDA-MB-231 (IC50, 48 hof Cisplatin is 5.29 µµ).In cell, investigation confirms that IrL1 nanoaggregates internalization via energy-dependent endocytosisundergo ferroptosis and ROS mediated cell death in MDA-MB-231 cells.Further, these in vivo studies using NOD-SCIDmice confirmed that IrL1exhibits a tendency to ablate tumors inoculated in mice models at therapeutically relevant doses.Thus, this comprehensive approach holds promise for expanding the repertoire of organometallic Ir(III) nanoaggregates with adaptable characteristics, thereby advancing their clinical utility of nanomedicine in the holistic treatment of metastatic 3Dtriple-negative breast tumor spheroids.

Encapsulation-induced hypsochromic shift of emission properties from a cationic Ir(III) complex in a hydrogen-bonded organic cage: A theoretical study.

Encapsulation of coordination complexes within the confined spaces of self-assembled hosts is an effective method for creating supramolecular assemblies with distinct chemical and physical properties. Recent studies with calix-resorcin[4]arene hydrogen-bonded hexameric capsules revealed that encapsulated metal complexes exhibit enhanced and blue-shifted photoluminescence compared to their unencapsulated forms. The photophysical change has been hypothetically attributed to encapsulation-induced confinement, which isolates the metal complex from the solvent, suppressing stabilization of the excited state of the guest by solvent reorganization and structural relaxation, and altering the local environment, such as solvent polarity and viscosity, around the guest. In this study, density-functional theory calculations were conducted to explore how encapsulation affects the photophysical properties of a cationic iridium complex within a hydrogen-bonded hexameric capsule. The encapsulation-induced emission shift was analyzed by separating it into three factors: suppression of solvent reorganization, suppression of structural relaxation of the complex, and electronic interactions between the complex and the capsule. The findings indicate that the photoluminescence modulation is driven by the electronic interaction between the host and guest, which affects the energy levels of the molecular orbitals involved in the T1 excited state and the suppression of excited-state structural relaxation of the Ir complex due to the presence of the host. This study advances our understanding of the photophysical dynamics of coordination complexes within the confined spaces of hexameric capsules, providing a valuable approach for tuning the excited state properties of guest molecules.

Computational analysis of molecular details on the interaction of C,N-cyclometalated 2H-indazole Ru(II) and Ir(III) complexes with cancer protein targets

A small library of different C,N-cyclometalated complexes of Ru(II) and Ir(III) with 2H-indazole ligand were investigated for their potential as inhibitors for protein targets that are known to play crucial roles in various cancer pathways. These targets play key roles in cell proliferation, apoptosis, cell migration, angiogenesis, inflammation, cell differentiation and in the activation of pro-inflammatory cytokines, etc. With experimental evidences available on the inhibition potential of these metal complexes, detailed molecular mechanisms of these metal complexes and their significant interactions that modulate the functions of cancer protein targets are not available and this forms the core of this investigation. Ten different protein targets were identified and the initial screening was done through molecular docking and the results have identified 4WOY, a receptor protein of Drp1 that plays crucial roles in mitochondrial fission process. Further investigations on the interaction of the proposed metal complexes as inhibitors for the above identified protein target were carried out through molecular docking and dynamic simulation studies. The possible interactions along with their energetics were analysed and discussed in detail.

A Pair of Deep Red Phosphorescent Responsive Emissive Cyclometalated Iridium (III) Complexes as Carbonic Anhydrase Inhibitor and Effective Theranostic Photosensitizer

ABSTRACTHerein, two deep red phosphorescent responsive emissive cyclometalated iridium (III) complexes with CAIX inhibition moiety was designed and synthesized; they can penetrate into living cells quickly and mainly located in the lysosome. They showed a strong binding affinity towards CAIX in vitro and effectively reduced cellular expression of CAIX. Moreover, the tethered CAIX‐inhibition moiety of benzene sulfonamide can decrease the inherent cytotoxicity of Ir(III) complex towards normal cells and improve killing selectivity towards cancer cells in dark; Ir3 and Ir4 exhibit approximately five to eight times higher killing selectivity than that of cisplatin; they exhibit satisfied photodynamic therapy effect under irradiation of 425 nm, ultimately resulting in apoptosis of cancer cell, which is accompanied with weakening of extracellular acidification, increased inhibition of cellular CAIX expression, significant loss of mitochondrial membrane potential, and elevated level of reactive oxygen. Herein, our work may demonstrate that combination of inhibition CAIX and metal photosensitizer may provide a promising strategy for constructing a novel theranostic platform.

Rational Design of Biocompatible Ir(III) Photosensitizer to Overcome Drug-Resistant Cancer via Oxidative Autophagy Inhibition.

Autophagy is a crucial quality control mechanism that degrades damaged cellular components through lysosomal fusion with autophagosomes. However, elevated autophagy levels can promote drug resistance in cancer cells, enhancing their survival. Downregulation of autophagy through oxidative stress is a clinically promising strategy to counteract drug resistance, yet precise control of oxidative stress in autophagic proteins remains challenging. Here, a molecular design strategy of biocompatible neutral Ir(III) photosensitizers is demonstrated, B2 and B4, for precise reactive oxygen species (ROS) control at lysosomes to inhibit autophagy. The underlying molecular mechanisms for the biocompatibility and lysosome selectivity of Ir(III) complexes are explored by comparing B2 with the cationic or the non-lysosome-targeting analogs. Also, the biological mechanisms for autophagy inhibition via lysosomal oxidation are explored. Proteome analyses reveal significant oxidation of proteins essential for autophagy, including lysosomal and fusion-mediator proteins. These findings are verified in vitro, using mass spectrometry, live cell imaging, and a model SNARE complex. The anti-tumor efficacy of the precise lysosomal oxidation strategy is further validated in vivo with B4, engineered for red light absorbance. This study is expected to inspire thetherapeutic use of spatiotemporal ROS control for sophisticated modulation of autophagy.

Acceptorless Dehydrogenation of Glycerol Catalysed by Ir(III) Complexes with Carbohydrate‐Functionalised Ligands: A Sweet Pathway to Produce Hydrogen and Lactic Acid

AbstractGlycerol, a by‐product of biodiesel production, has gained prominence as a precious platform chemical. To enhance the economic viability of the biodiesel production process and address the surplus of glycerol production, it is essential to transform it into value‐added products. In this context, homogeneous catalysis offers a promising avenue for glycerol valorisation. In this study, we introduce a family of iridium complexes bearing picolineamidate ligands with glucose‐functionalised substituents as novel homogeneous catalysts for glycerol to hydrogen and lactic acid conversion. These complexes exhibit high activity (conversion up to 53.3 %) and 99 % selectivity after 24 hours of reaction (TOFMAX=159 h−1, TON24h=2498). Notably, the reaction occurs under ambient air and at milder temperature conditions (120 °C) compared to other catalysts. These efforts in glycerol valorisation contribute to reducing biodiesel production costs, increasing the competitiveness of biofuels against petroleum‐based liquid fuels, giving rise to H2, through a global process with negative carbon dioxide emission, and lactic acid utilizable, among other, as a monomer for the synthesis of biodegradable plastics.

Mitochondrial Viscosity Probes: Iridium(III) Complexes Induce Apoptosis in HeLa Cells.

Mitochondrial viscosity has emerged as a promising biomarker for diseases such as cancer and neurodegenerative disorders, yet accurately measuring viscosity at the subcellular level remains a significant challenge. In this study, we synthesized and characterized three cyclometalated iridium(III) complexes (Ir1-Ir3) containing 5-fluorouracil derivatives as ligands. Among these, Ir1 selectively induced apoptosis in HeLa cells by increasing mitochondrial production of reactive oxygen species (ROS), which triggered a cascade of events leading to mitochondrial dysfunction. Additionally, the fluorescence lifetime of Ir1 demonstrated high sensitivity to intracellular viscosity changes, enabling real-time fluorescence lifetime imaging microscopy (FLIM) of cellular micro-viscosity during apoptosis. These findings underscore the potential of cyclometalated Ir(III) complexes for both therapeutic and diagnostic applications at the subcellular level.