Luminescent Cyclometalated Iridium Research Articles

Photophysical properties and photosensitizing abilities for hydrogen evolution reactions of robust cyclometalated iridium(III) complexes with 5,5′-bis(trifluoromethyl)-2,2′-bipyridine

Two luminescent cyclometalated iridium(III) complexes coordinated with electron-withdrawing 5,5′-bis(trifluoromethyl)-2,2′-bipyridine (dCF3bpy) ligand [Ir(C^N)2(dCF3bpy)]PF6 {H-C^N = 2-phenylpyridine (Hppy) for [1]PF6 and 2-(2,4-difluorophenyl)pyridine (HF2ppy) for [2]PF6}, which work as the robust photosensitizers, were synthesized and characterized by experimental and theoretical analyses. Obtained [1]PF6 and [2]PF6 showed yellow light emissions (559 and 578 nm, respectively) with relatively long lifetimes (728 and 739 nsec, respectively) at room temperature in CH2Cl2. Density functional theory (DFT) calculations clarified that these emissions were assigned as the phosphorescence derived from the mixed metal-ligand-to-ligand charge transfer (MLLCT) excited states. Potential photoredox abilities of [1]PF6 and [2]PF6 as the photosensitizers were also closely investigated by cyclic voltammetries (CVs), Stern-Volmer plots, and photochemical hydrogen evolution reactions. The results of these experiments indicated that [1]PF6 and [2]PF6 have substantial photosensitizing abilities; (i) reductive quenching of excited states of [1]PF6 and [2]PF6 by triethylamine (TEA) were observed in 10% aqueous THF, (ii) the systems involving of [1]PF6 (or [2]PF6), K2PtCl4, and TEA, which were served as the photosensitizer, H2 evolution catalyst, and sacrificial donor, respectively, showed highly efficient H2 evolution activities, and (iii) [1]PF6 and [2]PF6 have good durabilities in the photochemical H2 evolution reactions for a long time. The turnover numbers (TONs) of H2 evolution based on [1]PF6 and [2]PF6 at 96 h of irradiation were reached at 758 and 832 TONs, respectively, which were higher than that based on a well-known photosensitizer [Ir(ppy)2(bpy)]PF6 (659 TON).

Novel lysosome-targeted cyclometalated Iridium(III) anticancer complexes containing imine-N-heterocyclic carbene ligands: Synthesis, spectroscopic properties and biological activity

A series of luminescent cyclometalated iridium(III) anticancer complexes of the type [Ir(ppy)2(CˆN)]PF6− (where CˆN are imine-N-heterocyclic carbene ligands with various substituents and ppy is 2-phenylpyridine) was synthesized and fully characterized. All complexes Ir1–Ir5 showed potent cytotoxicity toward A549 and HeLa cancer cells with IC50 values ranging within 1.78–4.95 and 1.97–7.35 μM, respectively. Ir5 was particularly potent towards A549 cancer cells (IC50 = 1.78 μM) and had ca. 12-fold higher cytotoxicity than the clinical platinum drug cisplatin. Complexes Ir2 and Ir5 had moderate binding affinity to BSA. Mechanism studies showed that these complexes exerted their anticancer efficacy by cell-cycle arrest, inducing apoptosis, increasing the intracellular reactive oxygen species level, and reducing the mitochondrial membrane potential. Interestingly, the use of confocal microscopy provided insight into the microscopic mechanism of the most typical and active complex Ir5, which was found to enter A549 lung cancer cells mainly through an energy-dependent pathway and was located in the lysosome.

New luminescent cyclometalated iridium complexes prepared by the post-synthetic modification

Luminescent heteroleptic bis-cyclometalated iridium(III) complexes, [Ir(ppy)2(RPh-phen)](PF6) (Hppy=2-phenylpyridine; RPh-phen=5-(4′-R-substituted phenyl)-1,10-phenanthroline, R=H for 3, tBu for 4, and CF3 for 5), have been synthesized via Suzuki–Miyaura cross coupling reaction of the corresponding boronic acids with [Ir(ppy)2(X-phen)]Cl (X-phen=5-halogen-1,10-phenanthroline, X=Cl for 1 and Br for 2) and structurally characterized via single crystal X-ray diffraction analysis. Spectroscopic analyses and density functional calculations revealed that 3-5 in CH2Cl2 show intense orange emission with long emission lifetimes (τ=708–784ns) and high quantum yields (Φ=23.6–40.6%) that originate from a T1→S0 transition from the phen moiety to the Ir(ppy)2 moiety. Cyclic voltammetry analyses elucidated that 3-5 have reversible 1e− reduction and oxidation waves. The photosensitizing properties of 1-5 as well as [Ir(ppy)2(phen)](PF6) (6; phen=1,10-phenanthroline) were also analyzed via Stern-Volmer plots and photoreduction reactions of protons to yield hydrogen (H2). These results revealed that 3 is a promising photosensitizer for photochemical H2 evolution reaction that is comparable to 6.

Cyclometalated Iridium(III) Bipyridine-Phenylboronic Acid Complexes as Bioimaging Reagents and Luminescent Probes for Sialic Acids.

Sialic acids play important roles in mammalian development, cell-cell attachment, and signaling. As cancer cells utilize their overexpressed sialylated antigens to propagate metastases, the development of probes for sialic acids is of high importance. Herein, we report three luminescent cyclometalated iridium(III) bipyridine complexes bearing a phenylboronic acid (PBA) moiety. Spectrophotometric titrations revealed that the PBA complexes displayed higher binding affinity for the most common sialic acid N-acetylneuraminic acid (Neu5Ac) compared with simple sugars that are commonly found on glycoproteins. Notably, cellular imaging and uptake experiments showed that the PBA complexes were able to recognize cellular sialic acid residues, resulting in more efficient uptake than the boronic acid-free analogs. Additionally, one of the PBA complexes was shown to discriminate between cancerous and noncancerous cells.

Somatostatin receptor-targeted organometallic iridium(iii) complexes as novel theranostic agents.

A novel somatostatin receptor-targeted anticancer agent based on the conjugation of a highly cytotoxic and luminescent cyclometalated iridium(iii) complex to tumor-targeting vectors based on octreotide peptide has been described, and its potential for targeted theranostic applications has been demonstrated.

A long lifetime luminescent iridium(iii) complex chemosensor for the selective switch-on detection of Al3+ ions

A novel luminescent cyclometalated iridium(III) complex was synthesized and employed as a chemosensor for the detection of Al(3+) ions. Compared with common organic chemosensors, displays a larger Stokes shift and a long lifetime luminescence that allow to detect Al(3+) ions in fluorescent dye spiked strong fluorescence media and potentially be used in strongly autofluorescent biological samples.

New luminescent cyclometalated iridium(III) complexes containing fluorinated phenylisoquinoline-based ligands: Synthesis, structures, photophysical properties and DFT calculations

Two new fluorinated phenylisoquinoline-based iridium(III) complexes, [Ir(f2piq)2(bipy)][PF6] (3a) and [Ir(fmpiq)2(bipy)][PF6] (3b) (f2piq = 1-(2,4-difluorophenyl)isoquinoline, fmpiq = 1-(4-fluoro-2-methylphenyl)isoquinoline, bipy = 2,2′-bipyridine), have been synthesized and fully characterized. Single crystal X-ray diffraction study has been undertaken on complexes 3a and 3b, which show that each adopts the distorted octahedral coordination geometry with the cis-C,C′ and trans-N,N′ configuration. The photoluminescence spectra of 3a and 3b exhibit yellow and orange emission maxima at 584 and 600 nm, respectively. The frontier molecular orbital diagrams and the lowest-energy electronic transitions of 3a–3b have been calculated with density functional theory (DFT) and time-dependent DFT (TD-DFT). The absorption and emission spectra of complex 3b is red-shifted relative to those of complex 3a, as a consequence of the nature of the methyl group.

Cationic, luminescent cyclometalated iridium(III) complexes based on substituted 2-phenylthiazole ligands.

Ten cationic heteroleptic iridium(III) complexes, [Ir(emptz)2(N^N)](PF6) were prepared from a cyclometalated iridium bridged-chloride dimer involving two ethyl-4-methylphenylthiazole-5-carboxylate (emptz) ligands. One X-ray crystallographic study was undertaken where the ancillary N^N ligand was 4,7-diphenyl-1,10-phenanthroline and revealed the anticipated structure, showing a distorted octahedral coordination geometry at Ir(III). The complexes were visibly luminescent with modestly structured emission at 540-590 nm and lifetimes (60-340 ns) consistent with phosphorescence. TD-DFT calculations suggest that strong MLCT character contributes to the visible absorption characteristics, whilst the moderately structured emission profiles indicate a (3)MLCT/(3)IL admixture of states to the phosphorescence.

Phosphorescent Cyclometalated Iridium(III) Complexes That Contain Substituted 2‐Acetylbenzo[b]thiophen‐3‐olate Ligand for Red Organic Light‐Emitting Devices

We report the synthesis of a new class of thermally stable and strongly luminescent cyclometalated iridium(III) complexes 1-6, which contain the 2-acetylbenzo[b]thiophene-3-olate (bt) ligand, and their application in organic light-emitting diodes (OLEDs). These heteroleptic iridium(III) complexes with bt as the ancillary ligand have a decomposition temperature that is 10-20 % higher and lower emission self-quenching constants than those of their corresponding complexes with acetylacetonate (acac). The luminescent color of these iridium(III) complexes could be fine-tuned from orange (e.g., 2-phenyl-6-(trifluoromethyl)benzo[d]thiazole (cf3 bta) for 4) to pure red (e.g., lpt (Hlpt=4-methyl-2-(thiophen-2-yl)quinolone) for 6) by varying the cyclometalating ligands (C-deprotonated C^N). In particular, highly efficient OLEDs based on 6 as dopant (emitter) and 1,3-bis(carbazol-9-yl)benzene (mCP) as host that exhibit stable red emission over a wide range of brightness with CIE chromaticity coordinates of (0.67, 0.33) well matched to the National Television System Committee (NTSC) standard have been fabricated along with an external quantum efficiency (EQE) and current efficiency of 9 % and 10 cd A(-1) , respectively. A further 50 % increase in EQE (>13 %) by replacing mCP with bis[4-(6H-indolo[2,3-b]quinoxalin-6-yl)phenyl]diphenylsilane (BIQS) as host for 6 in the red OLED is demonstrated. The performance of OLEDs fabricated with 6 (i.e., [(lpt)2Ir(bt)]) was comparable to that of the analogous iridium(III) complex that bore acac (i.e., [(lpt)2 Ir(acac)]; 6a in this work) [Adv. Mater.- 2011, 23, 2981] fabricated under similar conditions. By using ntt (Hnnt=3-hydroxynaphtho[2,3-b]thiophen-2-yl)(thiophen-2-yl)methanone) ligand, a substituted derivative of bt, the [(cf3bta)2Ir(ntt)] was prepared and found to display deep red emission at around 700 nm with a quantum yield of 12 % in mCP thin film.

Visualization of Zn²⁺ ions in live zebrafish using a luminescent iridium(III) chemosensor.

A novel luminescent cyclometalated iridium(III) complex-based chemosensor (1) bearing a zinc-specific receptor, tris(2-pyridylmethyl)amine, and the 3-phenyl-1H-pyrazole ligand has been designed and synthesized. Upon the addition of Zn(2+) ions to a solution of iridium(III) complex 1, a pronounced luminescence color change from blue to green can be observed, which may be attributed to the suppression of photoinduced electron transfer upon complexation of complex 1 with Zn(2+) ions. The interaction of iridium(III) complex 1 with Zn(2+) ions was investigated by UV-vis absorption titration, emission titration, and (1)H NMR titration. Furthermore, the iridium(III) complex 1 exhibited good selectivity for Zn(2+) over 13 other common metal ions, including K(+), Ag(+), Na(+), Ni(2+), Fe(3+), Hg(2+), Cd(2+), Mg(2+), Ca(2+), Cu(2+), Mn(2+), Co(2+), and Pb(2+) ions. The practical application of the iridium(III) complex 1 in visualizing intracellular Zn(2+) distribution in live zebrafish was also demonstrated.

Accurate simulation of geometry, singlet-singlet and triplet-singlet excitation of cyclometalated iridium(III) complex

In the current contribution, we present a critical study of the theoretical protocol used for the determination of the electronic spectra properties of luminescent cyclometalated iridium(III) complex, [Ir(III)(ppy)₂H₂dcbpy]⁺ (where, ppy = 2-phenylpyridine, H₂dcbpy = 2,2'-bipyridine-4,4'-dicarboxylic acid), considered as a representative example of the various problems related to the prediction of electronic spectra of transition metal complex. The choice of the exchange-correlation functional is crucial for the validity of the conclusions that would be drawn from the numerical results. The influence of the exchange-correlation on geometry parameter and absorption/emission band, the role of solvent effects on time-dependent density function theory (TD-DFT) calculations, as well as the importance of the chosen proper procedure to optimize triplet excited geometry, have been thus examined in detail. From the obtained results, some general conclusions and guidelines are presented: i) PBE0 functional is the most accurate in prediction of ground state geometry; ii) the well-established B3LYP, B3P86, PBE0, and X3LYP have similar accuracy in calculation of absorption spectrum; and iii) the hybrid approach TD-DFT//CIS gives out excellent agreement in the evaluation of triplet excitation energy.

Phosphorescent proteins for bio-imaging and site selective bio-conjugation of peptides and proteins with luminescent cyclometalated iridium(iii) complexes

A new bio-conjugation reaction for site selective modification of proteins and peptides with phosphorescent iridium(III) complexes has been developed; the Ir(III)-modified proteins and peptides display long emission lifetimes and large Stoke shifts that can be used for bio-imaging studies.

A Luminescent Cyclometalated Iridium(III) Complex Accumulates in Mitochondria and Induces Mitochondrial Shortening by Conjugation to Specific Protein Targets

We report the cellular properties of a luminescent cyclometalated iridium(III) complex, [Ir(pq)(2)(phen-ITC)](PF(6)) (Ir-ITC; Hpq=2-phenylquinoline, phen-ITC=5-isothiocyanate-1,10-phenanthroline), that efficiently and specifically labels mitochondria in living mammalian cells. Ir-ITC can be covalently conjugated to its protein targets, and its luminescence survived cell lysis, protein extraction, and gel electrophoresis under denaturing conditions. The conjugation of Ir-ITC with live-cell proteins is rapid and highly selective; the process requires active cellular metabolism, as the conjugation is abolished at nonphysiological temperature or in the presence of sodium azide. Based on measurements of the luminescence intensity, we have devised a biochemical fractionation procedure that allows the enrichment of the conjugated proteins, and their subsequent separation by two-dimensional gel electrophoresis (2DGE). Luminescent protein spots were picked from the gel and analyzed by mass spectrometry; this resulted in the identification of 46 proteins. Many of the strongly luminescently labeled proteins are mitochondrial proteins. One of the targets is VDAC1 (voltage-dependent anion channel 1). Consistent with known phenotypes of VDAC1 deregulation, prolonged exposure of cells to Ir-ITC led to significant mitochondrial shortening and fragmentation. As far as we know, this is the first report on the molecular characterization of the interactions of a luminescent dye with its biological targets. As many biological dyes exhibit specific intracellular staining patterns, the identification of their molecular targets can help elucidate the mechanisms behind their staining specificities and cytotoxicity. We believe our biochemical approach can be applied to identify the targets of a wide range of fluorescent and luminescent probes.

Phosphorescence Imaging of Living Cells with Amino Acid-Functionalized Tris(2-phenylpyridine)iridium(III) Complexes

A series of nine luminescent cyclometalated octahedral iridium(III) tris(2-phenylpyridine) complexes has been synthesized, functionalized with three different amino acids (glycine, alanine, and lysine), on one, two, or all three of the phenylpyridine ligands. All starting complexes and final compounds have been fully analyzed by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy, and photophysical data have been obtained for all the mono-, bis-, and tri- substituted iridium(III) complexes. Cellular uptake and localization have been studied with flow cytometry and confocal microscopy, respectively. Confocal experiments demonstrate that all nine substituted iridium(III) complexes show variable uptake in the tumor cells. The monosubstituted iridium(III) complexes give the highest cellular uptake, and the series substituted with lysines shows the highest toxicity. This systematic study of amino acid-functionalized Ir(ppy)(3) complexes provides guidelines for further functionalization and possible implementation of luminescent iridium complexes, for example, in (automated) peptide synthesis or biomarker specific targeting.

Luminescent iridium(III) arylbenzothiazole complexes: Photophysics, electrochemistry, bioconjugation, and cellular uptake

Three luminescent cyclometalated iridium(III) diimine complexes [Ir(bsn)2(N^N)](PF6) (Hbsn=2-(1-naphthyl)benzothiazole; N^N=5-amino-1,10-phenanthroline (phen-NH2) (1), 5-isothiocyanato-1,10-phenanthroline (phen-NCS) (2), and N-butyl-N′-1,10-phenanthrolin-5-yl thiourea (phen-TU-Bt) (3)) have been synthesized and characterized. Complex 1 is a precursor complex of complex 2, and the isothiocyanate group of complex 2 enables it to function as a biological labeling reagent. To investigate its reactivity towards the primary amine group, complex 2 was reacted with a model substrate n-butylamine, resulting in the formation of complex 3. The photophysical and electrochemical properties of these complexes have been investigated. Upon photoexcitation, these complexes displayed intense and long-lived luminescence in fluid solutions at 298K and in butyronitrile glass at 77K. In view of the structured emission profiles and the long emission lifetimes, the emission of these complexes has been assigned to a triplet intraligand (3IL) (π→π∗)(bsn) excited state, probably with mixing of some triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Ir)→π∗(N^N)) character. Owing to the specific reactivity of the isothiocyanate group towards primary amines, complex 2 was conjugated to various proteins and polymers. Photoexcitation of these conjugates resulted in intense and long-lived 3IL (π→π∗)(bsn) emission in aqueous buffer at 298K. Additionally, the uptake of complexes 1–3 by HeLa cells has been investigated by various methods. Furthermore, the cytotoxicity of the complexes and the polymeric conjugates towards the cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay.

A thiocyanate-bridging dimeric cyclometalated iridium(III) complex: Synthesis, structure and phosphorescence behaviours towards metal ions

A new neutral dimeric cyclometalated iridium complex containing bridging thiocyanate ligands, [{Ir(μ-SCN)(pqcm) 2 } 2 ] ( 1 , pqcmH = 2-phenyl-quinoline-4- carboxylic acid methyl ester), has been synthesized and structurally characterized. The photoluminescence (PL) spectrum of 1 shows emission maximum at 638 nm with a lifetime of 0.11 μs and the PL quantum yield is ca. 0.012. The phosphorescence behaviours of 1 towards different solvents and metal ions were also investigated and the strong phosphorescence quenching by acetonitrile and two equivalents of Hg 2+ , Cu 2+ and Ag + ions were observed. A neutral dimeric cyclometalated iridium complex containing bridging thiocyanate ligands has been synthesized and structurally characterized, and show a short lifetime of 0.11 μs and the quenching of phosphorescence in the presence of acetonitrile or two equivalents of Hg 2+ , Cu 2+ and Ag + ions. ► Luminescent cyclometalated iridium(III) complexes. ► Cyclometalated iridium(III) thiocyanate-bridging dimer. ► Short lifetime and the quenching of phosphorescence. ► Phosphorescence behaviours towards metal ions.

Design of cyclometalated iridium(III) polypyridine complexes as luminescent biological labels and probes

The interesting emission properties of cyclometalated iridium(III) polypyridine complexes, originated from a range of excited states, have been well documented. The intense and long-lived emission of these complexes has been exploited in various areas of research including photovoltaic cells, chemosensors, and light-emitting devices. Additionally, there is an emerging interest in the applications of these luminescent complexes in various biological studies. In this paper, we summarize our recent work on the utilization of luminescent cyclometalated iridium(III) polypyridine complexes as biomolecular and cellular probes.

Evidence for Strong Mixing Between the LC and MLCT Excited States in Some Heteroleptic Iridium (III) Complexes

The synthesis, structure and photophysical properties of series of new luminescent cyclometalated Iridium (III) complexes are reported. The cyclometalated ligand used here is 2-aryl imidazole and the auxiliary ligand is acetyl acetone (acac). The crystal structure of the complex (dmdpi)(2)Ir(acac) (5) show that the Iridium(III) ion resides in a distorted octahedral environment. All complexes exhibit bright photoluminescence (PL) at room temperature and (fpdmdmpi)(2)Ir(acac) 4 has a high solution PL quantum efficiency of 0.56. The role played by electron releasing and electron withdrawing substituents of the 2-arylimidazole ligands towards the stability of HOMO and how the substituent influences the luminescent behaviour are discussed. Furthermore those substituents have effect on the contribution to mixing between (3)(π-π*) and (3)(MLCT) for the lowest excited states.

Ultrabright planar optodes for luminescence life-time based microscopic imaging of O 2 dynamics in biofilms

New transparent optodes for life-time based microscopic imaging of O 2 were developed by spin-coating a μm-thin layer of a highly luminescent cyclometalated iridium(III) coumarin complex in polystyrene onto glass cover slips. Compared to similar thin-film O 2 optodes based on a ruthenium(II) polypyridyl complex or a platinum(II) porphyrin, the new planar sensors have i) higher brightness allowing for much shorter exposure times and thus higher time resolution, ii) more homogeneous and smaller pixel to pixel variation over the sensor area resulting in less noisy O 2 images, and iii) a lower temperature dependency simplifying calibration procedures. We used the new optodes for microscopic imaging of the spatio-temporal O 2 dynamics at the base of heterotrophic biofilms in combination with confocal imaging of bacterial biomass and biofilm structure. This allowed us to directly link biomass distribution to O 2 distribution under both steady state and non-steady state conditions. We demonstrate that the O 2 dynamics in biofilms is governed by a complex interaction between biomass distribution, mass transfer and flow that cannot be directly inferred from structural information on biomass distribution alone.

Functionalization of luminescent cyclometalated iridium(iii) polypyridine complexes with a fluorous moiety: photophysics, protein-binding, bioconjugation, and cellular uptake properties

A new class of luminescent cyclometalated iridium(III) polypyridine fluorous complexes has been designed; the fluorous pendant not only plays an important role in the photophysical and biological properties of the complexes, but also allows the facile isolation of biomolecules labeled with these complexes with fluorous solid-phase extraction (FSPE).