Search Results (28)

Towards the efforts to expand the bioactivity and to reduce toxic and adverse properties of known metal-based drugs, various multinuclear complexes have recently been studied. They have shown enhancement of target specificity and selectivity. Different from small organic compounds and traditional metal-based complexes with anticancer activity, iridium(III) multinuclear or heteronuclear metallodrugs have confirmed potential advantages due to their unique biological and chemical diversities, better activity and different anticancer mechanisms. Ir(III) coordination compounds, similar to most Pt group compounds, are of excessive interest because of their potential cytotoxic activity, effective cellular uptake and tolerance by healthy cells. Although mononuclear Ir(III) complex compounds have been extensively studied as promising candidates for antitumor application, the research on the antineoplastic potential of homo- or hetero-multinuclear iridium(III) complexes is not as abundant; nevertheless, intensive investigations have been conducted in the recent years towards developing complexes that are anticipated to have improved therapeutic potential and biotarget selectivity. Multimetallic iridium(III) frameworks have offered interesting possibilities for designing new antitumor agents by exploiting the action of different metal cations at the same time. This method was very successful in the design of homo- and hetero-multinuclear cyclometalated and half-sandwich organometallic Ir(III) compounds. In the described background, many homonuclear and heteronuclear Ir(III) complexes have been estimated and have exposed promising advantages in cancer therapy. This review intends to summarize newly reported innovative and promising multinuclear Ir(III)-based complexes and to afford a wide-ranging overview of current development and perspectives for the practical impact of these complexes in the tumor therapy field. It is anticipated that this analysis will provide significant direction for the further progress of active homonuclear and heteronuclear iridium-based anticancer agents. Full article

This paper explores a novel synthesis and characterization of silica-coated gold nanorods (AuNRs) embedding a highly emissive cyclometalated iridium(III) complex, denoted as Ir₁. We investigate the optical properties and the interplay between the metal compound and gold plasmon, observing how the emission of Ir₁ incorporated into the nanoparticles shows two emission bands, one in the blue and the other in the green-orange range of the visible spectrum. To obtain a clearer picture of what we were observing, we synthesized analogous nanosystems, from which it was possible to highlight the effect of different features. Based on what we observed, we proposed that the fraction of the iridium(III) complex in direct contact with the surface of the gold nanoparticle undergoes a “demixing” of the excited state, which, for cyclometalated iridium complexes, is generally considered a mixed LC+MLCT state. This preliminary study sheds light on the complexity of the “talking” between a fluorophore and a plasmonic system, highlighting the importance of considering the emitter typology when modeling such systems. Full article

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. Full article

The N-oxide functional group has been exploited for synthetic strategies and drug design, and it has been utilized in imaging agents. Herein, we present rare examples of neutral heteroleptic cyclometallated Ir(III) compounds that contain an uncoordinated N-oxide functional group. These species, along with others described within, were verified by NMR, EA, HRMS, and single-crystal X-ray analysis. N-oxide-containing Ir(III) species were prepared selectively in high yields > 66% from chloro-bridged Ir(III) dimers with Acipimox, a picolinate-type ligand containing the N-oxide functional group. Non-N-oxide analogs were synthesized in a similar fashion (yields > 77%). Electrochemical comparison (cyclic voltammetry) indicates that the presence of an N-oxide functional group anodically shifts the reduction potential, suggesting that the N-oxide is acting as an electron-withdrawing group in these species. Crystallographic studies were pursued to examine the coordination behavior of these N-oxides compared to their non-oxidized congeners. The Ir(III) complexes with Acipimox indeed leave the N-oxide uncoordinated and exposed on the complexes. The uncoordinated N-oxide group is influential in directing the packing structures of these complexes directly through C-H···O and O···π interactions at the N-oxide. The crystallographic characterization of cationic Ir(III) compounds with uncoordinated nitrogen atoms is also presented. The C-H···N interactions between these complexes form a variety of dimers, finite chains, and continuous chains. Future work will focus on functionalizing the cationic Ir(III) species into their corresponding N-oxide derivatives and rigorously characterizing how the N-oxide functional group impacts the optical properties of transition metal compounds in both cationic and neutral complexes. Full article

The aerobic photooxidation of sulfides into sulfoxides in eco-friendly solvents, notably water, at room temperature, represents a significant interest in the domain of synthetic chemistry. This study introduces four highly stable hexadentate Ir(III) complexes: [Ir(fpqen)](PF₆) (1), [Ir(btqen)](PF₆) (2), [Ir(bmpqen)](PF₆) (3), and [Ir(bnqen](PF₆) (4) (where bfpqen is N,N′-bis(2-(4-fluorophenyl)quinolin-8-yl)ethane-1,2-diamine, btqen is N,N′-bis(2-(4-tolyl)quinolin-8-yl)ethane-1,2-diamine, bmpqen is N,N′-bis(2-(4-methoxyphenyl)quinolin-8-yl)ethane-1,2-diamine, and bnqen is N,N′-bis(2-naphthylquinolin-8-yl)ethane-1,2-diamine). These complexes were synthesized utilizing an in situ inter-ligand C-N cross-coupling photoreaction of the precursors [Ir(L)₂(en)](PF₆) (L is 2-(4-fluorophenyl)quinoline, (2-(4-tolyl)quinoline, 2-(4-methoxyphenyl)quinoline or 2-naphthylquinoline, and en is 1,2-diamine) under benign conditions. This methodology furnishes a valuable and complementary approach for the in situ generation of multidentate complexes through a post-coordination inter-ligand-coupling strategy under mild conditions. Moreover, these hexadentate Ir(III) complexes exhibit pronounced catalytic activity and chemo-selectivity toward the aerobic photooxidations of sulfides into sulfoxides in aqueous media at room temperature, offering a new avenue for the sustainable synthesis of sulfoxides. Full article

In this work, we report on the synthesis and characterization of six new iridium(III) complexes of the type [Ir(C^N)₂(N^N)]⁺ using 2-phenylpyridine (C1–3) and its fluorinated derivative (C4–6) as cyclometalating ligands (C^N) and R-phenylimidazo(4,5-f)1,10-phenanthroline (R = H, CH₃, F) as the ancillary ligand (N^N). These luminescent complexes have been fully characterized through optical and electrochemical studies. In solution, the C4–6 series exhibits quantum yields (Ф) twice as high as the C1–3 series, exceeding 60% in dichloromethane and where ³MLCT/³LLCT and ³LC emissions participate in the phenomenon. These complexes were employed in the active layer of light-emitting electrochemical cells (LECs). Device performance of maximum luminance values of up to 21.7 Lx at 14.7 V were observed for the C2 complex and long lifetimes for the C1–3 series. These values are counterintuitive to the quantum yields observed in solution. Thus, we established that the rigidity of the system and the structure of the solid matrix dramatically affect the electronic properties of the complex. This research contributes to understanding the effects of the modifications in the ancillary and cyclometalating ligands, the photophysics of the complexes, and their performance in LEC devices. Full article

Cyclometallated iridium(III) and platinum(II) complexes are intensely used in optoelectronics for their photophysical properties and ability to convert excitons from singlet to triplet state, thus improving the device efficiency. In this contribution, we report the multi-steps synthesis of an electrodeficient dipyridylbenzene-like terdentate ligand [N^C^N], namely 2′,6′-dimethyl-2,3′:5′,2″-terpyridine (6), with 18% overall yield. Compound 6 has been employed to synthesize two phosphorescent complexes of platinum(II) and iridium(III), namely compounds 7 and 8, respectively. Both complexes have been characterized by NMR and high resolution mass spectrometry, and demonstrate high luminescence quantum yields in a deaerated solution at room temperature, with 18% and 61% for 7 and 8, respectively. If the iridium(III) complex displays similar emission properties to [Ir(dpyx)(ppy)Cl] (dpyx = 3,5-dimethyl-2,6-dipyridylbenzene and ppy = 2- phenylpyridine), the platinum(II) derivative, with λ_em = 470 nm, is a rare example of a fluorine atom-free blue emitting [N^C^N]PtCl complex. Full article

Four iridium(III) dyes functionalized with aldehyde functional group in the cyclometalating (C^N) ligands, bearing either diethyl [2,2′-bipyridine]-4,4′-dicarboxylate or tetraethyl [2,2′-bipyridine]-4,4′-diylbis(phosphonate) anchoring groups, coded as Ir1–Ir4, are synthesized and explored as photosensitizers. The synthetic route is described and all of the complexes are characterized with respect to their electrochemical and photophysical properties. Density functional theory (DFT) calculation was used to gain insight into the factors responsible for the photocatalytic properties of Ir1–Ir4 as effective photosensitizers for photocatalytic hydrogen generation. Relative to common iridium(III) dyes, such as [Ir(ppy)₂(dcbpy)]⁺ (ppy = 2-phenylpyridine), the absorption spectra of our dyes are broader, which is attributed to the extended π-conjugation in their C^N ligands. All of the new iridium(III) dyes were used as photosensitizers for visible-light driven hydrogen production by attaching to platinized TiO₂ nanoparticles (Pt–TiO₂) in the presence of sacrificial electron donor (SED) of ascorbic acid (AA) in a purely aqueous solution. A H₂ turnover number (TON) up to 5809 was demonstrated for 280 h irradiation. Complexes with tetraethyl [2,2′-bipyridine]-4,4′-diylbis(phosphonate) anchoring groups were found to outperform those with classical diethyl [2,2′-bipyridine]-4,4′-dicarboxylate, which may be one of the important steps in developing high-efficiency iridium(III) photosensitizers in water splitting hydrogen generation. Full article

Photodynamic therapy (PDT), a noninvasive method for cancer therapy, involves the generation of reactive oxygen species (ROS) by the photochemical excitation of photosensitizers (PSs) to induce cell death in cancer cells. A variety of PS including porphyrin derivatives and metal complexes such as iridium (Ir) complexes have been reported. In clinical trials, red-near infrared (NIR) light (650–900 nm) is preferred for the excitation of PSs due to its deeper penetration into tissues compared with visible light (400–500 nm). To overcome this limitation, we established a PDT system that uses cyclometalated iridium(III) (Ir(III)) complexes that are excited with blue light in the wireless power transmission (WPT) system. To achieve this, we developed a light-emitting diode (LED) light device equipped with a receiver coil that receives electricity from the transmitter coil through magnetic resonance coupling. The LEDs in the receiving device use blue light (470 nm) to irradiate a given Ir(III) complex and excite triplet oxygen (³O₂) to singlet oxygen (¹O₂) which induces cell death in HeLa S3 cells (human cervical carcinoma cells). The results obtained in this study suggest that WPT-based PDT represents a potentially new method for the treatment of tumors by a non-battery LED, which are otherwise difficult to treat by previous PDT systems. Full article

Two differently substituted pyrazole ligands have been investigated with regard to the topology of their Pt complexes: upon deprotonation, two mononuclear 1:2 Pt^II-pyrazole complexes—one of the sterically unhindered 4-Me-pzH and one of the bulky 3,5-^tBu-pzH (pzH = pyrazole)—yield the corresponding 1:2 Pt^II-pyrazolato species; the former a triangular, trinuclear metallacycle (1), and the latter a dinuclear, half-lantern species (2) formed via the unprecedented cyclometallation of a butyl group. Stoichiometric oxidation of the colorless Pt^II₂ complex produces the deep-blue, metal–metal bonded Pt^III₂ analog (3) with a rarely encountered unsymmetrical coordination across the Pt-Pt bond. All three complexes have been characterized by single crystal X-ray structure determination, ¹H-NMR, IR, and UV-vis-NIR spectroscopic methods. The XPS spectra of the Pt^II₂ and Pt^III₂ species are also reported. Density functional theory calculations were carried out to investigate the electronic structure, spectroscopic properties, and chemical bonding of the new complexes. The calculated natural population analysis charges and Wiberg bonding indices indicate a weak σ-interaction in the case of 2 and a formal Pt-Pt single bond in 3. Full article

Three novel Ir(III) complexes, (ppy)₂Ir(L-alanine) (Ir1) (ppy = 2-phenylpyridine), (F₄ppy)₂Ir(L-alanine) (Ir2) (F₄ppy = 2-(4-fluorophenyl)pyridine), and (F_2,4,5ppy)₂Ir(L-alanine) (Ir3) (F_2,4,5ppy = 2-(2,4,5-trifluorophenyl)pyridine), based on simple L-alanine as ancillary ligands were synthesized and investigated. Due to the introduction of fluorine substituents on the cyclometalated ligands, complexes Ir1–Ir3 exhibited yellow to sky-blue emissions (λ_em = 464–509 nm) in acetonitrile solution. The photoluminescence quantum yields (PLQYs) of Ir1–Ir3 ranged from 0.48–0.69, of which Ir3 with sky-blue luminescence had the highest PLQY of 0.69. The electrochemical study and density functional theory (DFT) calculations show that the highest occupied molecular orbital (HOMOs) energy of Ir1–Ir3 are stabilized by the introduction of fluorine substituents on the cyclometalated ligands, while L-alanine ancillary ligand has little contribution to HOMOs and lowest unoccupied molecular orbitals (LUMOs). Moreover, Ir1–Ir3 presented an excellent response to Cu²⁺ with a high selectivity, strong anti-interference ability, and short response time. Such a detection was based on significant phosphorescence quenching of their emissions, showing the potential application in chemosensors for Cu²⁺. Full article

Herein the reaction mechanism and the origin of stereoselectivity of asymmetric hydrogenation of oximes to hydroxylamines catalyzed by the cyclometalated iridium (III) complexes with chiral substituted single cyclopentadienyl ligands (Ir catalysts A1 and B1) under acidic condition were unveiled using DFT calculations. The catalytic cycle for this reaction consists of the dihydrogen activation step and the hydride transfer step. The calculated results indicate that the hydride transfer step is the chirality-determining step and the involvement of methanesulfonate anion (MsO⁻) in this reaction is of importance in the asymmetric hydrogenation of oximes catalyzed by A1 and B1. The calculated energy barriers for the hydride transfer steps without an MsO⁻ anion are higher than those with an MsO⁻ anion. The differences in Gibbs free energies between TSA5−1fR/TSA5−1fS and TSB5−1fR/TSB5−1fS are 13.8/13.2 (ΔΔG^‡ = 0.6 kcal/mol) and 7.5/5.6 (ΔΔG^‡ = 1.9 kcal/mol) kcal/mol for the hydride transfer step of substrate protonated oximes with E configuration (E−2a−H⁺) with MsO⁻ anion to chiral hydroxylamines product R−3a/S−3a catalyzed by A1 and B1, respectively. According to the Curtin–Hammet principle, the major products are hydroxylamines S−3a for the reaction catalyzed by A1 and B1, which agrees well with the experimental results. This is due to the non-covalent interactions among the protonated substrate, MsO⁻ anion and catalytic species. The hydrogen bond could not only stabilize the catalytic species, but also change the preference of stereoselectivity of this reaction. Full article

Heteroleptic cyclometalated iridium (III) complexes (1–3) containing di-pyridylamine motifs were prepared in a stepwise fashion. The presence of the di-pyridylamine ligands tunes their electronic and optical properties, generating blue phosphorescent emitters at room temperature. Herein we describe the synthesis of the mononuclear iridium complexes [Ir(ppy)₂(DPA)][OTf] (1), (ppy = phenylpyridine; DPA = Dipyridylamine) and [Ir(ppy)₂(DPA-PhI)][OTf] (2), (DPA-PhI = Dipyridylamino-phenyliodide). Moreover, the dinuclear iridium complex [Ir(ppy)₂(L)Ir(ppy)₂][OTf]₂ (3) containing a rigid angular ligand “L = 3,5-bis[4-(2,2′-dipyridylamino)phenylacetylenyl]toluene” and displaying two di-pyridylamino groups was also prepared. For comparison purposes, the related dinuclear rhodium complex [Rh (ppy)₂(L)Rh(ppy)₂][OTf]₂ (4) was also synthesized. The x-ray molecular structure of complex 2 was reported and confirmed the formation of the target molecule. The rhodium complex 4 was found to be emissive only at low temperature; in contrast, all iridium complexes 1–3 were found to be phosphorescent in solution at 77 K and room temperature, displaying blue emissions in the range of 478–481 nm. Full article

Tumor cells are well adapted to grow in conditions of variable oxygen supply and hypoxia by switching between different metabolic pathways. However, the regulatory effect of oxygen on metabolism and its contribution to the metabolic heterogeneity of tumors have not been fully explored. In this study, we develop a methodology for the simultaneous analysis of cellular metabolic status, using the fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactor NAD(P)H, and oxygen level, using the phosphorescence lifetime imaging (PLIM) of a new polymeric Ir(III)-based sensor (PIr3) in tumors in vivo. The sensor, derived from a polynorbornene and cyclometalated iridium(III) complex, exhibits the oxygen-dependent quenching of phosphorescence with a 40% longer lifetime in degassed compared to aerated solutions. In vitro, hypoxia resulted in a correlative increase in PIr3 phosphorescence lifetime and free (glycolytic) NAD(P)H fraction in cells. In vivo, mouse tumors demonstrated a high degree of cellular-level heterogeneity of both metabolic and oxygen states, and a lower dependence of metabolism on oxygen than cells in vitro. The small tumors were hypoxic, while the advanced tumors contained areas of normoxia and hypoxia, which was consistent with the pimonidazole assay and angiographic imaging. Dual FLIM/PLIM metabolic/oxygen imaging will be valuable in preclinical investigations into the effects of hypoxia on metabolic aspects of tumor progression and treatment response. Full article

With an appropriate mixture of cyclometalating and ancillary ligands, based on simple structures (commercial or easily synthesized), it has been possible to design a family of eight new Ir(III) complexes (1A, 1B, 2B, 2C, 3B, 3C, 3D and 3E) useful as luminescent materials in LEC devices. These complexes involved the use of phenylpyridines or fluorophenylpyridines as cyclometalating ligands and bipyridine or phenanthroline-type structures as ancillary ligands. The emitting properties have been evaluated from a theoretical approach through Density Functional Theory and Time-Dependent Density Functional Theory calculations, determining geometric parameters, frontier orbital energies, absorption and emission energies, injection and transport parameters of holes and electrons, and parameters associated with the radiative and non-radiative decays. With these complexes it was possible to obtain a wide range of emission colours, from deep red to blue (701–440 nm). Considering all the calculated parameters between all the complexes, it was identified that 1B was the best red, 2B was the best green, and 3D was the best blue emitter. Thus, with the mixture of these complexes, a dual host–guest system with 3D-1B and an RGB (red–green–blue) system with 3D-2B-1B are proposed, to produce white LECs. Full article