Sterically Hindered Tetradentate [Pt(O

Described here are sterically hindered tetradentate [Pt(O^N^C^N)] emitters (Pt-1, Pt-2, and Pt-3) developed for stable and high-performance green phosphorescent organic light-emitting diodes (OLEDs). These Pt(II) emitters exhibit strong saturated green phosphorescence (λmax = 517-531 nm) in toluene and mCP thin films with emission quantum yields as high as 0.97, radiative rate constants (kr) as high as 4.4-5.3 × 105 s-1 and reduced excimer emission, and with a preferential horizontally oriented transition dipole ratio of up to 84%. Theoretical calculations show that p-(hetero)arene substituents at the periphery of the ligand scaffolds in Pt-1, Pt-2, and Pt-3 can i) enhance the spin-orbit coupling (SOC) between the lower singlet excited states and the T1 state, and S0→Sn (n = 1 or 2) transition dipole moment, and ii) introducing additional SOC activity and the bright 1ILCT[π(carbazole)→π*(N^C^N)] excited state (Pt-2 and Pt-3), which are the main contributors to the increased kr values. Utilizing these tetradentate Pt(II) emitters, green phosphorescent OLEDs are fabricated with narrow-band electroluminescence (FWHM down to 36 nm), high external quantum efficiency, current efficiency up to 27.6% and 98.7 cd A-1, and an unprecedented device lifetime (LT95) of up to 9270 h at 1000 cd m-2 under laboratory conditions.

Targeting unfolded protein response using albumin-encapsulated nanoparticles attenuates temozolomide resistance in glioblastoma.

BACKGROUND: Chemoresistant cancer cells frequently exhibit a state of chronically activated endoplasmic reticulum (ER) stress. Engaged with ER stress, the unfolded protein response (UPR) is an adaptive reaction initiated by the accumulation of misfolded proteins. Protein disulfide isomerase (PDI) is a molecular chaperone known to be highly expressed in glioblastomas with acquired resistance to temozolomide (TMZ). We investigate whether therapeutic targeting of PDI provides a rationale to overcome chemoresistance. METHODS: The activity of PDI was suppressed in glioblastoma cells using a small molecule inhibitor CCF642. Either single or combination treatment with TMZ was used. We prepared nanoformulation of CCF642 loaded in albumin as a drug carrier for orthotopic tumour model. RESULTS: Inhibition of PDI significantly enhances the cytotoxic effect of TMZ on glioblastoma cells. More importantly, inhibition of PDI is able to sensitise glioblastoma cells that are initially resistant to TMZ treatment. Nanoformulation of CCF642 is well-tolerated and effective in suppressing tumour growth. It activates cell death-triggering UPR beyond repair and induces ER perturbations through the downregulation of PERK signalling. Combination treatment of TMZ with CCF642 significantly reduces tumour growth compared with either modality alone. CONCLUSION: Our study demonstrates modulation of ER stress by targeting PDI as a promising therapeutic rationale to overcome chemoresistance.

Gold(I) Multi-Resonance Thermally Activated Delayed Fluorescent Emitters for Highly Efficient Ultrapure-Green Organic Light-Emitting Diodes.

Acceleration of singlet-triplet intersystem crossings (ISC) is instrumental in bolstering triplet exciton harvesting of multi-resonance thermally activated delayed fluorescent (MR-TADF) emitters. This work describes a simple gold(I) coordination strategy to enhance the spin-orbit coupling of green and blue BN(O)-based MR-TADF emitters, which results in a notable increase in rate constants of the spectroscopically observed ISC process to 3×109  s-1 with nearly unitary ISC quantum yields. Accordingly, the resultant thermally-stable AuI emitters attained large values of delayed fluorescence radiative rate constant up to 1.3×105 /1.7×105  s-1 in THF/PMMA film while preserving narrowband emissions (FWHM=30-37 nm) and high emission quantum yields (ca. 0.9). The vapor-deposited ultrapure-green OLEDs fabricated with these AuI emitters delivered high luminance of up to 2.53×105  cd m-2 as well as external quantum efficiencies of up to 30.3 % with roll-offs as low as 0.8 % and long device lifetimes (LT60 ) of 1210 h at 1000 cd m-2 .

Vitamin D Promotes Remyelination by Suppressing c-Myc and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury.

Demyelination due to oligodendrocytes loss occurs after traumatic spinal cord injury (TSCI). Several studies have suggested the therapeutic potential of vitamin D (VitD) in demyelinating diseases. However, experimental evidence in the context of TSCI is limited, particularly in the presence of prior VitD-deficiency. In the present study, a contusion and a transection TSCI rat model were used, representing mild and severe injury, respectively. Motor recovery was assessed in rats with normal VitD level or with VitD-deficiency after 8 weeks' treatment post-TSCI (Cholecalciferol, 500 IU/kg/day). The impact on myelin integrity was examined by transmission electron microscopy and studied in vitro using primary culture of oligodendrocytes. We found that VitD treatment post-TSCI effectively improved hindlimb movement in rats with normal VitD level irrespective of injury severity. However, cord-transected rats with prior deficiency did not seem to benefit from VitD supplementation. Our data further suggested that having sufficient VitD was essential for persevering myelin integrity after injury. VitD rescued oligodendrocytes from apoptotic cell death in vitro and enhanced their myelinating ability towards dorsal root axons. Enhanced myelination was mediated by increased oligodendrocyte precursor cells (OPCs) differentiation into oligodendrocytes in concert with c-Myc downregulation and suppressed OPCs proliferation. Our study provides novel insights into the functioning of VitD as a regulator of OPCs differentiation as well as strong preclinical evidence supporting future clinical testing of VitD for TSCI.

Highly Robust CuI -TADF Emitters for Vacuum-Deposited OLEDs with Luminance up to 222 200 cd m-2 and Device Lifetimes (LT90 ) up to 1300 hours at an Initial Luminance of 1000 cd m-2.

A critical step in advancing the practical application of copper-based organic light-emitting diodes (OLEDs) is to bridge the large gap between device efficiency and operational stability at practical luminance. Described is a panel of air- and thermally stable two-coordinate CuI emitters featuring bulky pyrazine- (PzIPr) or pyridine-fused N-heterocyclic carbene (PyIPr*) and carbazole (Cz) ligands with enhanced amide-Cu-carbene bonding interactions. These CuI emitters display thermally activated delayed fluorescence (TADF) from the 1 LL'CT(Cz→PzIPr/PyIPr*) excited states across the blue to red regions with exceptional radiative rate constants of 1.1-2.2×106  s-1 . Vapour-deposited OLEDs based on these CuI emitters showed excellent external quantum efficiencies and luminance up to 23.6 % and 222 200 cd m-2 , respectively, alongside record device lifetimes (LT90 ) up to 1300 h at 1000 cd m-2 under our laboratory conditions, highlighting the practicality of the CuI -TADF emitters.

Photoinduced Hydroarylation and Cyclization of Alkenes with Luminescent Platinum(II) Complexes.

Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410 nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.

Stable, High-Efficiency Voltage-Dependent Color-Tunable Organic Light-Emitting Diodes with a Single Tetradentate Platinum(II) Emitter Having Long Operational Lifetime.

Voltage-dependent, color-tunable organic light-emitting diodes (OLEDs) are appealing tools that can be used for the visualization of electronic output signal of sensors. Nonetheless, the literature-reported color-tunable OLEDs that have a simple single-cell device structure suffer from relatively low efficiency, pronounced efficiency roll-off, color-aging, and short operation lifetime, all of which limit their practical applications. Here, a novel co-host-in-double-emissive-layer (CHIDEL) device, designed to enhance the performance of color-tunable OLEDs with the use of a single tetradentate Pt[O^ N^ C^ N] emitter, is described. When Pt-X-2 is used as a single emitter in an optimized CHIDEL device, a white OLED with tunable Commission International de I'Eclairage (CIE) coordinates from (0.47, 0.44) at 3 V to (0.36, 0.48) at 11 V, a high color rendering index of 82, and high external quantum efficiency (EQE) of up to 20.75% can be achieved. By using Pt-X-4 as a single emitter, the voltage-dependent color-tunable CHIDEL device, with CIE coordinates shifted from (0.56, 0.43) at 3 V to (0.42, 0.55) at 11 V, demonstrates a high luminance of beyond 90 000 cd m-2 and a high EQE of 23.23% at a luminance of 1300 cd m-2 . A long-lifetime time to 90% of the initial luminance (LT90 ) of almost 20 000 h is demonstrated for the color-tunable OLED with Pt-X-4 emitting dopant.

High-Efficiency Solution-Processed Organic Light-Emitting Diodes with Tetradentate Platinum(II) Emitters.

The realization of high-efficiency solution-processed organic light-emitting diodes (OLEDs) using phosphorescent tetradentate Pt(II) emitters and bipolar organic hosts is demonstrated in this work. To investigate the effect of organic host on the platinum dopant, the performances of solution-processed Pt-OLEDs with various combinations between four tetradentate Pt(II) emitters, including two newly developed tetra-Pt-S2 and tetra-Pt-S3 and three bipolar organic hosts m-TPAPy, o-TPAPy, and o-CzPy, have been analyzed and compared. Among the tetradentate Pt(II) complexes studied in this work, tetra-Pt-S3 exhibited the best electroluminescent performance attributable to its bulky molecular scaffold structure, high emission quantum yield, and good solubility in common organic solvents. High external quantum efficiencies (EQEs) of up to 22.4% were achieved in the solution-processed OLED with tetra-Pt-S3 emitter and m-TPAPy host at the dopant concentration of 4 wt %. At a high luminance of 1000 cd m-2, the EQE of this device decreased slightly to 21.0%.

Strongly Luminescent Tungsten Emitters with Emission Quantum Yields of up to 84 %: TADF and High-Efficiency Molecular Tungsten OLEDs.

Metal-TADF (thermally activated delayed fluorescence) emitters hold promise in the development of next generation light-emitting materials for display and lighting applications, examples of which are, however, largely confined to CuI and recently AuI , AgI , and AuIII emitters. Herein is described the design strategy for an unprecedented type of metal-TADF emitter based on inexpensive tungsten metal chelated with Schiff base ligand that exhibit high emission quantum yields of up to 56 % in solutions and 84 % in thin-film (5 wt % in 1,3-bis(N-carbazolyl)benzene, mCP) at room temperature. Femtosecond time-resolved emission (fs-TRE) spectroscopy and DFT calculations were undertaken to decipher the TADF properties. Solution-processed OLEDs fabricated with the W-TADF emitter demonstrated external quantum efficiency (EQE) and luminance of up to 15.6 % and 16890 cd m-2 , respectively.

Luminescent ruffled iridium(iii) porphyrin complexes containing N-heterocyclic carbene ligands: structures, spectroscopies and potent antitumor activities under dark and light irradiation conditions.

A panel of iridium(iii) porphyrin complexes containing axial N-heterocyclic carbene (NHC) ligand(s) were synthesized and characterized. X-ray crystal structures of the bis-NHC complexes [IrIII(ttp)(IMe)2]+ (2a), [IrIII(oep)(BIMe)2]+ (2d), [IrIII(oep)(I i Pr)2]+ (2e) and [IrIII(F20tpp)(IMe)2]+ (2f) display ruffled porphyrin rings with mesocarbon displacements of 0.483-0.594 Å and long Ir-CNHC bonds of 2.100-2.152 Å. Variable-temperature 1H NMR analysis of 2a reveals that the macrocycle porphyrin ring inversion takes place in solution with an activation barrier of 40 ± 1 kJ mol-1. The UV-vis absorption spectra of IrIII(por)-NHC complexes display split Soret bands. TD-DFT calculations and resonance Raman experiments show that the higher-energy Soret band is derived from the 1MLCT dπ(Ir) → π*(por) transition. The near-infrared phosphorescence of IrIII(por)-NHC complexes from the porphyrin-based 3(π, π*) state features broad emission bands at 701-754 nm with low emission quantum yields and short lifetimes (Φ em < 0.01; τ < 4 µs). [IrIII(por)(IMe)2]+ complexes (por = ttp and oep) are efficient photosensitizers for 1O2 generation (Φ so = 0.64 and 0.88) and are catalytically active in the light-induced aerobic oxidation of secondary amines and arylboronic acid. The bis-NHC complexes exhibit potent dark cytotoxicity towards a panel of cancer cells with IC50 values at submicromolar levels. The cytotoxicity of these complexes could be further enhanced upon light irradiation with IC50 values as low as nanomolar levels in association with the light-induced generation of reactive oxygen species (ROS). Bioimaging of [IrIII(oep)(IMe)2]+ (2c) treated cells indicates that this Ir complex mainly targets the endoplasmic reticulum. [IrIII(oep)(IMe)2]+ catalyzes the photoinduced generation of singlet oxygen and triggers protein oxidation, cell cycle arrest, apoptosis and the inhibition of angiogenesis. It also causes pronounced photoinduced inhibition of tumor growth in a mouse model of human cancer.

Luminescent Iridium(III) Pyridinium-Derived N-Heterocyclic Carbene Complexes as Versatile Photoredox Catalysts.

The development of novel luminescent iridium(III) complexes with highly tunable emission energy and versatile applications is of particular importance. In this Communication, a series of luminescent iridium(III) complexes supported by chromophoric pyridinium-derived N-heterocyclic carbene (NHC) ligands that display tunable emission from 516 to 682 nm were prepared. These complexes can be used as photocatalysts in photooxidation and photoreduction reactions and could have potential applications in pH sensing.

Tripodal S-Ligand Complexes of Copper(I) as Catalysts for Alkene Aziridination, Sulfide Sulfimidation, and C-H Amination.

Copper(I) complexes of tris(thioimidazolyl)borates (R'TmR), including [Cu(TmPh)(PR″3)] (R″ = Ph, Cu1; Cy, Cu2) and [Cu(R'TmPh)(PR″3)]+ (R' = N-methylimidazole; R″ = Ph, Cy) were prepared and characterized by spectroscopic methods. The X-ray crystal structures of Cu1 and Cu2 feature a tripodal TmPh ligand coordinated in κ3-S,S,S mode. Using Cu2 as a catalyst (loading: 1 mol %), the aziridination of styrenes and sulfimidation of thioanisoles with PhI═NTs at RT for 3 and 0.5 h, respectively, both resulted in product yields of up to 99%. Cu2 also catalyzed intramolecular amination of the aryl C-H bond of vinyl azides with up to 98% yield. DFT calculations were performed to gain insight into the mechanism of the Cu2-catalyzed aziridination reaction.

Stable luminescent iridium(iii) complexes with bis(N-heterocyclic carbene) ligands: photo-stability, excited state properties, visible-light-driven radical cyclization and CO2 reduction, and cellular imaging.

A new class of cyclometalated Ir(iii) complexes supported by various bidentate C-deprotonated (C^N) and cis-chelating bis(N-heterocyclic carbene) (bis-NHC) ligands has been synthesized. These complexes display strong emission in deaerated solutions at room temperature with photoluminescence quantum yields up to 89% and emission lifetimes up to 96 µs. A photo-stable complex containing C-deprotonated fluorenyl-substituted C^N shows no significant decomposition even upon irradiation for over 120 h by blue LEDs (12 W). These, together with the strong absorption in the visible region and rich photo-redox properties, allow the bis-NHC Ir(iii) complexes to act as good photo-catalysts for reductive C-C bond formation from C(sp3/sp2)-Br bonds cleavage using visible-light irradiation (λ > 440 nm). A water-soluble complex with a glucose-functionalized bis-NHC ligand catalysed a visible-light-driven radical cyclization for the synthesis of pyrrolidine in aqueous media. Also, the bis-NHC Ir(iii) complex in combination with a cobalt catalyst can catalyse the visible-light-driven CO2 reduction with excellent turnover numbers (>2400) and selectivity (CO over H2 in gas phase: >95%). Additionally, this series of bis-NHC Ir(iii) complexes are found to localize in and stain endoplasmic reticulum (ER) of various cell lines with high selectivity, and exhibit high cytotoxicity towards cancer cells, revealing their potential uses as bioimaging and/or anti-cancer agents.

A Novel Tetradentate Ruthenium(II) Complex Containing Tris(2- Pyridylmethyl)amine (tpa) As An Inhibitor Of Beta-amyloid Fibrillation.

We report herein the synthesis and application of a novel tetradentate ruthenium(II) complex 1 containing a tris(2-pyridylmethyl)amine (tpa) ligand as an inhibitor of ß-amyloid fibrillogenesis. [Ru(tpa)(bt)]ClO(4) 1 (bt =2-acetylbenzo[b]thiophene-3-olate) showed significant inhibition of Aß(1-40) peptide aggregation in vitro, which was confirmed by a Thioflavin T assay and transmission electron microscopy imaging.

A robust and efficient cobalt molecular catalyst for CO2 reduction.

Visible-light driven CO2 reduction is considered to be a sustainable energy source. However, earth-abundant molecular catalysts with high efficiency and robustness towards solar-driven CO2 reduction are limited. Herein, we report a cobalt complex supported by a tetradentate tripodal ligand, which demonstrates catalytic solar-driven CO2 reduction with TON(CO) > 900 over 70 h in the presence of a photosensitizer.