Iridium Complexes Research Articles

Double Catalytic Activity Unveiled: Synthesis, Characterization, and Catalytic Applications of Iridium Complexes in Transfer Hydrogenation and Photomediated Transformations.

Iridium complexes have been demonstrated to be highly active catalysts for a wide variety of transformations. Their unique photophysical and photochemical properties render them as one of the most established photocatalysts. Moreover, iridium complexes are widely acknowledged for their efficiency in transfer hydrogenation reactions. However, the development of iridium complexes able to promote both traditional organometallic catalysis and photocatalysis is scarce. Thus, the design of iridium-based catalysts is still an active area of research. In this context, we targeted the synthesis of a family of Ir-Cp* systems to explore their (photo)catalytic applications. Here, we describe the synthesis, structural characterization, and photophysical properties of iridium complexes of formula [IrCp*Cl(N^O)]. These complexes have been applied with a double catalytic function, in transfer hydrogenation for carbonyl reduction and in different photomediated transformations.

An Iridium Complex as Bidentate Halogen Bond-Based Anion Receptor Featuring an IncreasedOptical Response.

We present a luminescent Ir(III) complex featuring a bidentate halogen bond donor site capable of strong anion binding. The tailor-made Ir(III)(L)2 moiety offers a significantly higher emission quantum yield (8.4 %) compared to previous Ir(III)-based chemo-sensors (2.5 %). The successful binding of chloride, bromide and acetate is demonstrated using emission titrations. These experiments reveal association constants of up to 1.6×105 M-1. Furthermore, a new approach to evaluate the association constant by utilizing the shift of the emission was used for the first time. The experimentally observed characteristics are supported by quantum chemical simulations.

Electrogenerated Chemiluminescence Biosensor for Quantization of Matrix Metalloproteinase-3 in Serum via Target-Induced Cleavage of Oligopeptide

A highly sensitive and selective electrogenerated chemiluminescence (ECL) biosensor was developed for the determination of matrix metalloproteinase 3 (MMP-3) in serum via the target-induced cleavage of an oligopeptide. One ECL probe (named as Ir-peptide) was synthesized by covalently linking a new cyclometalated iridium(III) complex ([(3-pba)2Ir(bpy-COOH)](PF6)) (3-pba = 3-(2-pyridyl) benzaldehyde, bpy-COOH = 4′-methyl-2,2′-bipyridine-4-carboxylic acid) with an oligopeptide (CGVPLSLTMGKGGK). An ECL biosensor was fabricated by firstly casting Nafion and gold nanoparticles (AuNPs) on a glassy carbon electrode and then self-assembling both of the ECL probes, 6-mercapto-1-hexanol and zwitterionic peptide, on the electrode surface, from which the AuNPs could be used to amplify the ECL signal and Ir-peptide could serve as an ECL probe to detect the MMP-3. Thanks to the MMP-3-induced cleavage of the oligopeptide contributing to the decrease in ECL intensity and the amplification of the ECL signal using AuNPs, the ECL biosensor could selectively and sensitively quantify MMP-3 in the concentration range of 10–150 ng·mL−1 and with both a limit of quantification (26.7 ng·mL−1) and a limit of detection (8.0 ng·mL−1) via one-step recognition. In addition, the developed ECL biosensor showed good performance in the quantization of MMP-3 in serum samples, with a recovery of 92.6% ± 2.8%–105.6% ± 5.0%. An increased level of MMP-3 was found in the serum of rheumatoid arthritis patients compared with that of healthy people. This work provides a sensitive and selective biosensing method for the detection of MMP-3 in human serum, which is promising in the identification of patients with rheumatoid arthritis.

α-Alkylation and Asymmetric Transfer Hydrogenation of Tetralone via Hydrogen Borrowing and Dynamic Kinetic Resolution Strategy Using a Single Iridium(III) Complex.

Here we present a novel strategy for the synthesis of enantiomerically enriched tetrahydronaphthalen-1-ols. The reaction proceeds via an alkylation (via hydrogen borrowing) and ammonium formate-mediated asymmetric transfer hydrogenation (via dynamic kinetic resolution), giving alkylated tetralols in high yields and good enantio- and diastereoselectivity across a diverse range of both alcohol and tetralone substrates. Additionally, these products were successfully derivatized to several complex molecules, demonstrating the utility of the tetrahydronaphthalen-1-ol.

Synthesis and performance of a nanosensing platform for homocysteine detection: A series of iridium(III) complexes containing aldehyde group as probe and MOF as supporting substrate

The low cost and simple detection method for Hcy (homocysteine) is highly desired in analytical and biological fields since Hcy has been regarded as a bio-marker for multiple diseases. In this work, five Ir(C^N)2(N^N)+ compounds having –CHO group in their C^N or N^N ligand were synthesized and tried for Hcy sensing. Electron-donating groups such as –NH2 and –CH3 were incorporated into the C^N or N^N ligand. Their geometric structure, electronic structure, and optical parameters (with or without Hcy) were analyzed and compared carefully to explore their Hcy sensing potential. The sensing mechanism was revealed by NMR titration and theoretical simulation as a cyclization reaction between the –CHO group and Hcy. The optimal compounds, which showed increased emission quantum yield (2.5-fold) and emission blue-shift (by ∼ 100 nm) upon Hcy, were then covalently grafted into a porous host bio-MOF-1. Linear working plots were fitted, with good selectivity, LOD of 0.15 μM, and response time of 33 s. The novelty of this work was the eye-sensitive emission color change of this nanosensing platform from red (without Hcy) to green (with Hcy).

Identification of Cellular Protein Targets of a Half-Sandwich Iridium(III) Complex Reveals Its Dual Mechanism of Action via Both Electrophilic and Oxidative Stresses.

Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C∧N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high-affinity targets. Upon iridium complex treatment, the folding activity of Heat Shock Protein HSP90 was inhibited in vitro and major cytoskeleton disorganization was observed. A wide array of imaging and biochemical methods validated selected targets and provided a multiscale overview of the effects of this complex on live human cells. We demonstrate that it behaves as a dual agent, inducing both electrophilic and oxidative stresses in cells that account for its cytotoxicity. The proposed methodological workflow can open innovative avenues in metallodrug discovery.

Monitoring the Mitochondrial Viscosity Changes During Cuproptosis with Iridium(III) Complex Probe via In Situ Phosphorescence Lifetime Imaging.

Cuproptosis is a novel copper-dependent form of programmed cell death, displaying important regulatory functions in many human diseases, including cancer. However, the relationship between the changes in mitochondrial viscosity, a key factor associated with cellular malfunction, and cuproptosis is still unclear. Herein, we prepared a phosphorescent iridium (Ir) complex probe for precisely monitoring the changes of mitochondrial viscosity during cuprotosis via phosphorescence lifetime imaging. The Ir complex probe possessed microsecond lifetimes (up to 1 μs), which could be easily distinguished from cellular autofluorescence to improve the imaging contrast and sensitivity. Benefiting from the long phosphorescence lifetime, excellent viscosity selectivity, and mitochondrial targeting abilities, the Ir complex probe could monitor the increase in the mitochondrial viscosity during cuproptosis (from 46.8 to 68.9 cP) in a quantitative manner. Moreover, through in situ fluorescence imaging, the Ir complex probe successfully monitored the increase in viscosity in zebrafish treated with lipopolysaccharides or elescolomol-Cu2+, which were well-known cuproptosis inducers. We anticipate that this new Ir complex probe will be a useful tool for in-depth understanding of the biological effects of mitochondrial viscosity during cuproptosis.

Synthesis, structure and effects of an azoimine functionalized iridium complex on cancer cells

A novel ligand L having azoimine bond with quinoline moiety reacts with [(2-ppy)2Ir(μ-Cl)]2 in dichloromethane medium to produce an iridium(III) complex of composition [Ir(2-ppy)2(L)]. Here, the iridium centre is bound to neutral bidentate N, N donating sites of the ligand (L), where the azo part of L is not involved in chelation. The ligand and complex are characterized by elemental analysis, NMR spectroscopy, ESI-MS mass spectrometry, FTIR, UV–Vis and luminescence spectroscopic techniques. The ligand structure and the geometry around iridium centre of complex [Ir(2-ppy)2(L)] is confirmed by the single-crystal X-ray diffraction (XRD) method. DFT studies were also performed to support the experimental aspects of the complex as well as electronic distribution in molecular orbitals of various energy states. The complex exhibits blue emission band at 428 nm with quantum yield (Φ) 0.136. Further, in vitro analysis of the anticancer activity of the complex was studied mainly with the MCF - 7 cell line. The results showed that the complex have good IC50 values when compared to the standard drug cisplatin.

Dual inhibition of oxidative phosphorylation and glycolysis to enhance cancer therapy

Dual suppression of oxidative phosphorylation (OXPHOS) and glycolysis can disrupt metabolic adaption of cancer cells, inhibiting energy supply and leading to successful cancer therapy. Herein, we have developed an α-tocopheryl succinate (α-TOS)-functionalized iridium(III) complex Ir2, a highly lipophilic mitochondria targeting anticancer molecule, could inhibit both oxidative phosphorylation (OXPHOS) and glycolysis, resulting in the energy blockage and cancer growth suppression. Mechanistic studies reveal that complex Ir2 induces reactive oxygen species (ROS) elevation and mitochondrial depolarization, and triggers DNA oxidative damage. These damages could evoke the cancer cell death with the mitochondrial-relevant apoptosis and autophagy. 3D tumor spheroids experiment demonstrates that Ir2 owned superior antiproliferation performance, as the potent anticancer agent in vivo. This study not only provided a new path for dual inhibition of both mitochondrial OXPHOS and glycolytic metabolisms with a novel α-TOS-functionalized metallodrug, but also further demonstrated that the mitochondrial-relevant therapy could be effective in enhancing the anticancer performance.

Light-harvesting iridium (III) complex-sensitized NiO photocathode for photoelectrochemical bioanalysis.

Anovel iridium (III) complex bearing boron dipyrromethene (Bodipy) as the light-harvesting antenna has been synthesized and is firstly employed as photosensitizer to assemble adye-sensitized NiO photocathode. The assembled photocathode exhibits significantly improved photoelectrochemical (PEC) performance. Integrating the prepared photocathode with hybridization chain reaction (HCR)--based signal amplification strategy, a cathodic PEC biosensor is proposed for the detection of microRNA-133a (miRNA-133a). In the presence of thetarget, HCR is triggered to form long duplex concatamers on the photocathode, which allows numerous manganese porphyrins (MnPP) to bind in the dsDNA groove. With the help of H2O2, MnPP with peroxidase-like activity catalyzes 4--chloro-1-naphthol (4-CN) to produce benzo--4--chlorohexadienone (4-CD) precipitate on the electrode, leading to a significant decrease of photocurrent signal. The decreased photocurrent correlates linearly with the target concentration from 0.1 fM to 1nM with a detection limit of 66.2 aM (S/N = 3). Theproposed PEC strategy exhibits delightful selectivity, reproducibility and stability.

Cyclometalated Iridium(III) Complexes Containing Viologen-Modified Phenylpyridine Ligands as Electroluminochromic Active Molecules for Information Display.

Electroluminochromic (ELC) materials have garnered significant research interest because of their potential applications in lighting, displaying, and sensing. These materials exhibit reversible modulation of photoluminescence under low-voltage stimuli. Here five phosphorescent iridium(III) complexes are reported featuring viologen-substituted 2-phenylpyridine (Vppy) ligands acting as electroactive components. Four of the complexes are bis-cyclometalated and coordinated with either neutral bipyridine derivatives or negatively charged 2-picolinate. The remaining complex is heteroleptic tris-cyclometalated, containing one Vppy and two 2-phenylquinoline ligands. Upon photoexcitation, the bis-cyclometalated complexes exhibit orange to red phosphorescence originating from mixed triplet metal-to-ligand charge transfer (3MLCT) and intraligand (3IL) dπ(Ir)/π(Vppy) → π*(Vppy) state, whereas the tris-cyclometalated complex is non-emissive due to a low Ir(IV/III) oxidation potential favoring oxidative quenching by the viologen pendants. When the cationic viologens are electrochemically reduced to their neutral form, the bis-cyclometalated complexes show a remarkable blue-shift in their phosphorescence maxima due to increased energy levels of the Vppy molecular orbitals. In the case of the tris-cyclometalated complex, reduction of the viologen groups interrupts the quenching process, leading to a luminescence turn-on. These complexes are used to develop ELC devices, which exhibit reversible luminescence response in terms of color or on-off switching under a low voltage of 2V.

Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

BackgroundBased on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment.MethodsGold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Iren-AuSiO2_COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Iren-AuSiO2_Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models.ResultsWe show efficient capability of Iren-AuSiO2_Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR+ tumor/PDGFRβ+ stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors.ConclusionsOur study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.

Rigidity‐Enhanced Narrowband Iridium(III) Complexes with Finely‐Optimized Emission Spectra for Efficient Pure‐Red Electroluminescence

AbstractAttaining phosphorescent materials with narrowband emission is crucial for advancing wide‐color‐gamut organic light‐emitting diode (OLED). Herein, a rigid modification strategy is introduced for iridium(III) complexes to achieve the narrowband red emission with negligible 0–1 peak. By introducing the rigid indolo[3,2,1‐jk]carbazole (ICz) into the cyclometalated ligand, Ir(III) complexes, ICziq‐Ir and ICzqz‐Ir, exhibit pure red phosphorescence with emission peaks at 608 and 613 nm and full widths at half‐maximum (FWHMs) of 37 and 38 nm (0.12 and 0.13 eV) in toluene, respectively. Furthermore, the specific site modification of ICzqz‐Ir greatly suppresses the high‐frequency vibration of the structure, resulting in the narrowband photoluminescent spectrum close to the Gaussian distribution with superior color purity. The OLEDs utilizing ICziq‐Ir and ICzqz‐Ir demonstrate maximum external quantum efficiencies of 21.4 and 17.8% as well as mild efficiency roll‐off. Remarkably, the electroluminescence spectra exhibit similar narrowband red emission with FWHMs of 37 and 43 nm and CIE coordinates of (0.65, 0.35) and (0.66, 0.34), attesting to the excellent color purity of the phosphorescent OLEDs.

Reconstructing the 3D Coordinates of Guest:Host OLED Blends with Single Atom Resolution.

The performance of electronic and semiconductor devices is critically dependent on the distribution of guest molecules or atoms in a host matrix. One prominent example is that of organic light-emitting diode (OLED) displays containing phosphorescent emitters, now ubiquitous in handheld devices and high-end televisions. In such OLEDs the phosphorescent guest [normally an iridium(III)-based complex] is typically blended into a host matrix, and charge injection and transport, exciton formation and decay, and hence overall device performance are governed by the distribution of the emissive guest in the host. Here high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) is used with depth sectioning to reconstruct the 3D distribution of emissive iridium(III) complexes, fac-tris(2-phenylpyridine)iridium(III) [Ir(ppy)3], blended into the amorphous host material, tris(4-carbazoyl-9-ylphenyl)amine (TCTA), by resolving the position of each single iridium(III) ion. It is found that most Ir(ppy)3 complexes are clustered with at least one other, even at low concentrations, and that for films of 20wt.% Ir(ppy)3 essentially all the complexes are interconnected. The results validate the morphology of blend films created using molecular dynamics simulations which mimic the evaporation film-forming process and are also consistent with the experimentally measured charge transport and photophysical properties.

Chemiluminescence and electrochemiluminescence of water-soluble iridium(III) complexes containing a tetraethylene-glycol functionalised triazolylpyridine ligand

BackgroundIridium(III) complexes, exhibiting high luminescence quantum yields and a wide range of emission colours, are promising alternatives to tris(2,2ʹ-bipyridine)ruthenium(II) for chemiluminescence (CL) and electrochemiluminescence (ECL) detection. This emerging class of reagent, however, is limited by the poor solubility of many iridium(III) complexes in aqueous solution, and lack of understanding of their remarkably variable selectivities towards different analytes. ResultsSeven [Ir(C^N)2(pt-TEG)]+ complexes, exhibiting a wide range of reduction potentials and emission energies, were examined with six model analytes. For CL, cerium(IV) was used as the oxidant. The alkylamine analytes generally produced greater CL and ECL with the more readily oxidised Ir(III) complexes (C^N = piq, bt, ppy), predominantly through the ‘direct’ pathway requiring oxidation of both metal complex and analyte. Aniline derivatives that did not also contain secondary or tertiary alkylamines elicited CL from the less readily oxidised complexes (C^N = df-ppy-CF3, df-ppy) via energy transfer. The most difficult to oxidise complexes (C^N = df(CF3)-ppy-Me, df(CN)-ppy) gave poor responses due to the limited potential window of the solvent and inefficiency of energy transfer to their high energy excited states. Greater CL and/or ECL intensities were generally obtained for each analyte with at least one Ir(III) complex than with [Ru(bpy)3]2+; superior limits of detection for two analytes were demonstrated. SignificanceThis exploration of CL/ECL in which the properties of luminophore, analyte and oxidant are all varied provides a new understanding of the influence of the metal-complex potentials and excited state energy on the light-producing and quenching pathways, and consequently, their distinct selectivity towards different analytes. These findings will guide the development of water-soluble Ir(III) complexes as CL and ECL reagents.

Dual-Emissive Iridium(III) Complexes and Their Applications in Biological Sensing and Imaging.

Phosphorescent iridium(III) complexes are widely recognized for their unique properties in the excited triplet state, making them crucial for various applications including biological sensing and imaging. Most of these complexes display single phosphorescence emission from the lowest-lying triplet state after undergoing highly efficient intersystem crossing (ISC) and ultrafast internal conversion (IC) processes. However, in cases where these excited-state processes are restricted, the less common phenomenon of dual emission has been observed. This dual emission phenomenon presents an opportunity for developing biological probes and imaging agents with multiple emission bands of different wavelengths. Compared to intensity-based biosensing, where the existence and concentration of an analyte are indicated by the brightness of the probe, the emission profile response involves modifications in emission color. This enables quantification by utilizing the intensity ratio of different wavelengths, which is self-calibrating and unaffected by the probe concentration and excitation laser power. Moreover, dual-emissive probes have the potential to demonstrate distinct responses to multiple analytes at separate wavelengths, providing orthogonal detection capabilities. In this concept, we focus on iridium(III) complexes displaying fluorescence-phosphorescence or phosphorescence-phosphorescence dual emission, along with their applications as biological probes for sensing and imaging.

Synthesis, spectroscopic characterizations and biological studies on gold(III), ruthenium(III) and iridium(III) complexes of trimethoprim antibiotic drug

Ruthenium(III), gold(III), and iridium(III) trimethoprim drug (TMP) complexes were synthesized and analyses via microanalytical approach (C, H, N analysis), magnetic, molar conductance, and FTIR, 1H NMR, XRD, and UV-Vis spectroscopy. Through two nitrogen atoms of –NH2 amino groups, the TMP drug coordinated as a bidentate ligand towards the corresponding three metal ions. The geometrical structure of the compounds ruthenium(III), gold(III), and iridium(III) is octahedral and consists of two TMP molecules, two coordinated chlorine atoms, and one uncoordinated chlorine atom. The antibacterial properties of TMP complexes have been investigated through the use of many bacterial species, including Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Additionally, the generated complexes' anticancer properties against HepG-2 (human hepatocellular carcinoma) and MCF-7 (human breast cancer cell line) have been assessed. In contrast to those of clinically used antibiotics, the inhibition zone of ruthenium and iridium(III) complexes was in the low efficiency range, and the antibacterial activity of gold(III) complexes was moderate. This article discusses the possibilities and prospects for this family of metallodrugs as antibacterial or anticancer medicines.
 KEY WORDS: Trimethoprim drug, Chelation, Gold, TEM, XRD, FTIR
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 701-714. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.12 

Synthesis, spectroscopic and biological characterizations of platinum(IV), ruthenium(III) and iridium(III) theophylline complexes

This study used micro-analyses, (FTIR, UV-Vis) spectra, magnetic, thermogravimetric, X-ray powder diffraction (XRD) patterns, and transmittance electron microscopy (TEM) techniques to characterize three synthesized theophylline (TPH) complexes with ruthenium(III), platinum(IV), and iridium(III) metal ions. The metal ions indicated above were found to align with the TPH drug chelate as a mono-dentate ligand via the deprotonated NH group at the nitrogen atom position N7, as verified by FTIR measurements. Additionally, the complexes conductivity and magnetic susceptibility were examined. The octahedral geometry for the synthesized complexes was proposed by the current data. Except for the iridium(III) complex, which has a non-electrolytic nature due to the presence of a chlorine atom inside the chelation sphere, the molar conductivity of the complexes in DMSO solution was electrolyte in nature. Theophylline complexes with a (metal: ligand) stoichiometry of 1:2 were produced. The TPH complexes have also been tested in vitro against G(+) bacteria (Bacillus subtilis and Staphylococcus Aureus) and G(-) bacteria (Pseudomonas aeruginosa and Escherichia coli) to evaluate their antibacterial efficacy. Human breast and liver cancer cell lines were used as a test for the TPH complexes in vitro anti-cancer properties.
 KEY WORDS: Theophylline, Metal ions, Chelation, Octahedral, Spectral analysis, Nano-particles, Biological evaluation
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 725-738. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.14

A Semi‐Automated, High‐Throughput Approach for the Synthesis and Identification of Highly Photo‐Cytotoxic Iridium Complexes

AbstractThe discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise‐and‐test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well‐tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure–activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi‐automated synthesise‐and‐test protocol to obtain multiplex data within 72 hours.

A Semi-Automated, High-Throughput Approach for the Synthesis and Identification of Highly Photo-Cytotoxic Iridium Complexes.

The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise-and-test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well-tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure-activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi-automated synthesise-and-test protocol to obtain multiplex data within 72 hours.