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The synthesis, structural characterization and photophysical properties of a series of platinum(II) complexes of benzannulated pincer-type diarylamido ligands are described. The ligands all contain tricyclic phenanthridine (3,4-benzoquinoline) rings as donor arms, which were elaborated into N∧N−∧O-coordinating β-enaminoketonato chelates via partial condensation with acetylacetone. The proligands are easily deprotonated, and metallation can be achieved under mild conditions using simple Pt(II) salts and Ag2O as a base. The resulting Pt(II) complexes exhibit strong metal-to-ligand charge-transfer absorptions in the region of ∼450–575 nm and are phosphorescent in solution at room temperature, emitting bright orange light (λmax ∼ 600 nm) with quantum yields of up to 16% and excited-state lifetimes on the order of ∼20 μs, representing significant improvements to these photophysical properties compared with many previously reported N∧N∧O or N∧N∧N-ligated systems. Computational modelling reveals that the lowest-lying triplet state is populated efficiently thanks to strong coupling between singlet and triplet excited state manifolds, as in cyclometallated compounds of Pt(II). Substituents (CH3, tBu, or CF3) in the 2-position of the phenanthridinyl unit are found to have little influence on the optical properties, but the emission is severely quenched when a methyl substituent is introduced ortho to the coordinating nitrogen. Molecular distortions in the excited state are shown to be primarily responsible for the quenching in this complex.

International audience; The synthesis and photophysical and chiroptical properties of novel aza[n]helicenes (6a-d, 10a,b, n = 4-7) substituted with one or two 2-pyridyl groups are described. The preparation was performed via an adapted Mallory reaction using aromatic imines as precursors. The obtained novel class of helical 2,2’-bipyridine ligands was then coordinated to Ru(bipy)(2)(2+) units, thus affording the first diastereomerically and enantiomerically pure [RuL(bipy)(2)](2+) (11a,c, L = 6a,c) or [Ru(2)L’(bipy)(4)](4+) (12, L’ = 10b) complexes. The topology and stereochemistry of these novel metal-based helical architectures were studied in detail, notably using X-ray crystallography. Interestingly, the coordination to ruthenium(II) enabled the preparation of fused multihelical systems incorporating aza- and ruthena-helicenes within the same scaffold. The photophysical, chiroptical, and redox properties of these complexes were examined in detail, and efficient redox-triggered chiroptical switching activity was evidenced.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel are established as the primary causative factor in the devastating lung disease cystic fibrosis (CF). More recently, cigarette smoke exposure has been shown to be associated with dysfunctional airway epithelial ion transport, suggesting a role for CFTR in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, the identification and characterization of a high throughput screening hit 6 as a potentiator of mutant human F508del and wild-type CFTR channels is reported. The design, synthesis, and biological evaluation of compounds 7-33 to establish structure-activity relationships of the scaffold are described, leading to the identification of clinical development compound icenticaftor (QBW251) 33, which has subsequently progressed to deliver two positive clinical proofs of concept in patients with CF and COPD and is now being further developed as a novel therapeutic approach for COPD patients.

The reduction of carbon dioxide into useful products such as fuels and chemicals is a topic of intense research activity at present, driven by the need to reduce atmospheric CO2 levels and avoid catastrophic temperature rises across the world. In this review, we consider a range of different technological approaches to CO2 conversion, their current status and the molecules which each approach is best suited to making. In Part I, the biological, catalytic and electrocatalytic routes are presented.

In this review, we consider a range of different technological approaches to carbon dioxide conversion, their current status and the molecules which each approach is best suited to making. Part II presents the photochemical, photoelectrochemical, plasma and microbial electrosynthetic routes to CO2 reduction and discusses the technological options together with proposals for future research needs from an industry perspective.

A novel dinuclear platinum(ii) complex featuring a ditopic, bis-tetradentate ligand has been prepared. The ligand offers each metal ion a planar O^N^C^N coordination environment, with the two metal ions bound to the nitrogen atoms of a bridging pyrimidine unit. The complex is brightly luminescent in the red region of the spectrum with a photoluminescence quantum yield of 83% in deoxygenated methylcyclohexane solution at ambient temperature, and shows a remarkably short excited state lifetime of 2.1 μs. These properties are the result of an unusually high radiative rate constant of around 4 × 105 s−1, a value which is comparable to that of the very best performing Ir(iii) complexes. This unusual behaviour is the result of efficient thermally activated reverse intersystem crossing, promoted by a small singlet–triplet energy difference of only 69 ± 3 meV. The complex was incorporated into solution-processed OLEDs achieving EQEmax = 7.4%. We believe this to be the first fully evidenced report of a Pt(ii) complex showing thermally activated delayed fluorescence (TADF) at room temperature, and indeed of a Pt(ii)-based delayed fluorescence emitter to be incorporated into an OLED., Efficient thermally activated delayed fluorescence (TADF) in a brightly luminescent diplatinum(ii) complex results in significant enhancement of the radiative decay rate.

International audience; The first enantiopure chiral-at-rhenium complexes of the form fac-ReX(CO) (:C^N) have been prepared, where :C^N is a helicene-N-heterocyclic carbene (NHC) ligand and X=Cl or I. These have complexes show strong changes in the emission characteristics, notably strongly enhanced phosphorescence lifetimes (reaching 0.7 ms) and increased circularly polarized emission (CPL) activity, as compared to their parent chiral models lacking the helicene unit. The halogen along with its position within the dissymmetric stereochemical environment strongly affect the photophysics of the complexes, particularly the phosphorescence quantum yield and lifetime. These results give fresh insight into fine tuning of photophysical and chiroptical properties of Re-NHC systems.

Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment. Humans sequester iron, manganese and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Commercially-used chelants have high binding affinities with a variety of metal ions, which may lead to antibacterial properties that mimic these innate immune processes. However, the modes of action of many of these chelating agents in bacterial growth inhibition and their selectivity in metal deprivation in cellulo remain ill-defined. We address this shortcoming by examining the effect of eleven chelators on Escherichia coli growth and their impact on the cellular concentration of five metals. Four distinct effects were uncovered: i) no apparent alteration in metal composition, ii) depletion of manganese alongside reductions in iron and zinc levels, iii) reduced zinc levels with a modest reduction in manganese, and iv) reduced iron levels coupled with elevated manganese. These effects do not correlate with the absolute known chelant metal ion affinities in solution, however, for at least five chelators for which key data are available, they can be explained by differences in the relative affinity of chelants for each metal ion. The results reveal significant insights into the mechanism of growth inhibition by chelants, highlighting their potential as antibacterials and as tools to probe how bacteria tolerate selective metal deprivation. IMPORTANCE Chelating agents are widely used in industry and consumer goods to control metal availability, with bacterial growth restriction as a secondary benefit for preservation. However, the antibacterial mechanism of action of chelants is largely unknown, particularly with respect to the impact on cellular metal concentrations. The work presented here uncovers distinct metal starvation effects imposed by different chelants on the model Gram-negative bacterium Escherichia coli. The chelators were studied both individually and in pairs with the majority producing synergistic effects in combinations that maximise antibacterial hostility. The judicious selection of chelants based on contrasting cellular effects should enable reductions in the quantities of chelant required in numerous commercial products and presents opportunities to replace problematic chemistries with biodegradable alternatives.

Introduction: The cannabinoid type 1 (CB1) receptor and cannabinoid type 2 (CB2) receptor are widely expressed in the body and anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are their best characterized endogenous ligands. The diacylglycerol lipases (diacylglycerol lipase alpha and diacylglycerol lipase beta) not only synthesize essentially all the 2-AG in the body but also generate other monoacylglycerols, including 2-linoleoylglycerol (2-LG). This lipid has been proposed to modulate endocannabinoid (eCB) signaling by protecting 2-AG from hydrolysis. However, more recently, 2-LG has been reported to be a CB1 antagonist. Methods: The effect of 2-LG on the human CB1 receptor activity was evaluated in vitro using a cell-based reporter assay that couples CB1 receptor activation to the expression of the β-lactamase enzyme. Receptor activity can then be measured by a β-lactamase enzymatic assay. Results: When benchmarked against 2-AG, AEA, and arachidonoyl-2′-chloroethylamide (a synthetic CB1 agonist), 2-LG functions as a partial agonist at the CB1 receptor. The 2-LG response was potentiated by JZL195, a drug that inhibits the hydrolysis of monoacylglycerols. The 2-LG response was also fully inhibited by the synthetic CB1 antagonist AM251 and by the natural plant derived antagonist cannabidiol. 2-LG did not potentiate, and only blunted, the activity of 2-AG and AEA. Conclusions: These results support the hypothesis that 2-LG is a partial agonist at the human CB1 receptor and capable of modulating the activity of the established eCBs.

International audience; We describe the preparation of helically chiral gold(I) complexes bearing a [5]helicenic-N-heterocyclic carbene ligand. They were successfully obtained as enantiopure compounds by semi-preparative chiral HPLC and their structural, chiroptical, and photophysical properties were subsequently investigated. Notably, strong electronic circular dichroism, dual emission from singlet and triplet states, with the timescale of the latter up to the millisecond range at room temperature, and moderate circularly phosphorescence were observed. The sigma-donating and pi-accepting properties of the constituent helical ortho-fused pi-conjugated carbene were investigated by classical quantitative analysis of the IR stretching frequencies and NMR characteristics of the corresponding Ir(CO)(2)Cl complex and selenourea.

In this work we present synthesis and an in-depth photophysical analysis of a di-Pt(II) complex with a ditopic bis-N^C^N ligand. The complex exhibits a dual luminescent behaviour by emitting simultaneously delayed fluorescence and phosphorescence. By comparing with the mono-Pt(II) analogue, we demonstrate that thermally activated delayed fluorescence (TADF) is turned on in the di-Pt(II) complex due to the occurrence of three main factors which are not verified in the mono-Pt(II) analogue: a larger singlet radiative rate (krS), a smaller singlet-triplet energy gap (ΔEST) and a longer phosphorescence decay lifetime (τPH). We observe similar trends among other di-Pt(II) complexes and concluded that bimetallic structures promote conditions favourable for TADF to occur. The diplatinum(II) complex also shows a long wavelength-emissive excimer which yields near infrared electroluminescence, λel = 805 nm, in a solution-processed OLED device with EQEmax = 0.51 %. We believe this is the highest efficiency reported to date for an excimer Pt(II) emitter with λel > 800 nm in a solution-processed OLED device.

In the epoxidation of ethylene to ethylene oxide using chemical looping, Ag is supported on strontium ferrite perovskite, where Ag acts as the catalyst while the perovskite acts as an oxygen carrier. This study explores how various oxygen carriers based on strontium ferrite affect chemical looping epoxidation. The structure of the oxygen carrier was varied by incorporating different ratios of two perovskite phases: cubic SrFeO3, and a layered Ruddlesden-Popper (RP) phase: Sr3Fe2O7. Maximum yield of ethylene oxide was obtained for the sample with 1:1 SrFeO3:RP ratio, leading to an increase in the yield of ethylene oxide around 4 times, compared to only SrFeO3 (i.e. 0.4–1.6% ethylene oxide yield). These results confirm a possibility of designing the oxygen carriers used in chemical looping epoxidation towards optimal performance. Such a design approach can be expanded to other chemical looping processes to tune the performance of oxygen carrier for the reaction in question.

A platform for investigating the impact of π-extension in benzannulated, anionic pincer-type N^N–^N-coordinating amido ligands and their Pt(II) complexes is presented. Based on bis(8-quinolinyl)amine, symmetric and asymmetric proligands bearing quinoline or π-extended phenanthridine (3,4-benzoquinoline) units are reported, along with their red-emitting, phosphorescent Pt(II) complexes of the form (N^N–^N)PtCl. Comparing the photophysical properties of complexes of (quinolinyl)amido ligands with those of π-extended (phenanthridinyl)amido analogues revealed a counterintuitive impact of site-selective benzannulation. Contrary to conventional assumptions regarding π-extension, and in contrast to isoenergetic lowest energy absorption bands and a red shift in fluorescence from the organic proligands, a blue shift of nearly 40 nm in the emission wavelength is observed for Pt(II) complexes with more extended bis(phenanthridinyl) ligand π-systems. Comparing the ground state and triplet excited state structures optimized from density functional theory (DFT) and time-dependent-DFT calculations, we trace this effect to a greater rigidity of the benzannulated complexes, resulting in a higher energy emissive triplet state, rather than to a significant perturbation of orbital energies caused by π-extension.

Curcumin has chemopreventive properties against a variety of tumours, but it has poor bioavailability. Two new bis‐cyclometallated iridium(III) complexes have been prepared, featuring the natural product curcumin (CUR) or its reduced form, tetrahydrocurcumin (THC), as bidentate, anionic O^O‐binding ligands. The iridium THC complex is highly luminescent in deoxygenated solution and efficiently generates singlet oxygen under aerated conditions, whereas in the curcumin analogue, other non‐radiative decay pathways are competitive. The complexes are rapidly taken up into a variety of human tumour cell lines from solutions of micromolar concentration. They have negligible cytotoxicity in the absence of irradiation. When briefly irradiated by visible light, Ir‐THC becomes highly phototoxic, inducing rapid apoptosis within 2 h. The results show the high potential of such complexes as sensitizers in photodynamic therapy (PDT).

Background: Although the liver is the primary organ of drug metabolism, the lungs also contain drug-metabolizing enzymes and may, therefore, contribute to the elimination of drugs. In this investigation, the Precision-cut Lung Slice (PCLS) technique was standardized with the aims of characterizing and comparing rat and human pulmonary drug metabolizing activity. Method: Due to the limited availability of human lung tissue, standardization of the PCLS method was performed with rat lung tissue. Pulmonary enzymatic activity was found to vary significantly with rat age and rat strain. The Dynamic Organ Culture (DOC) system was superior to well-plates for tissue incubations, while oxygen supply appeared to have a limited impact within the 4h incubation period used here. Results: The metabolism of a range of phase I and phase II probe substrates was assessed in rat and human lung preparations. Cytochrome P450 (CYP) activity was relatively low in both species, whereas phase II activity appeared to be more significant.Conclusion:PCLS is a promising tool for the investigation of pulmonary drug metabolism. The data indicates that pulmonary CYP activity is relatively low and that there are significant differences in enzyme activity between rat and human lung.

International audience; Two dyads containing tris-and tetrakis-meso-fluorenyl-substituted porphyrin and ethynylruthenium units, 1 and 2, were investigated by emission spectro-electrochemical (SEC) methods for their potential use as fluorescence switches. The ruthenium group as a potential electron donor and the porphyrin as a potential electron acceptor are connected by a phenylene bridge in 1 and by a fluorenylene bridge in 2. The new fluorenyl-linked dyad 2 was probed by UV-visible, near-infrared (NIR) and infrared (IR) absorption SEC methods, and the properties interpreted with the aid of hybrid-DFT computations, for comparison with reported data for 1. The porphyrin-based fluorescence of 1 decreased in intensity upon oxidation to 1 + and decreased further on oxidising 1 + to 1 2+. Negligible change in the fluorescence intensity of 2 was observed upon oxidation to 2 + but the intensity decreased upon subsequent oxidation of 2 + to 2 2+. These findings contrast with data reported for some other porphyrins appended with redox-active ruthenium or iron units, where fluorescence intensities increase upon oxidation of the peripheral metal centers, but they match data reported more recently for closely related arrays. A rationale for these apparently contrasting observations is proposed. A c c e p t e d m a n u s c r i p t

Two series of new apatite-type silicate materials were synthesised and characterised with the aim of achieving white light emission from single-phase phosphors. The Gd9.33(SiO4)6O2 host was doped systematically with Dy3+, Tb3+ and Eu3+ to tune the emission to the white light region. Eight new phosphors with emission very near the ideal white light point are reported. The best properties are found for the 0.5%Tb, 0.03%Eu co-doped Gd9.33(SiO4)6O2, with colour coordinates (0.340, 0.341) and a correlated colour temperature of 5190 K, corresponding to the white light region. The temporal decay of emission from the doped ions was measured following pulsed excitation of the Gd3+ host. An evaluation of energy transfer and quenching effects in the phosphors has been made based on the lifetimes so obtained. In particular, a comparison of the Eu3+ lifetimes in the Dy,Eu co-doped phosphors with those in the Tb,Eu-containing materials suggests quenching of the 5D0 excited state of Eu3+ by the Dy3+ ions. These observations imply that the combination of Eu3+ and Dy3+ ions may not provide optimal efficiencies in phosphors, and that the combination of Eu3+ and Tb3+ is likely to be superior for optimising the emission properties.

The synthesis and photophysical properties of 22 platinum(ii) complexes featuring N^N^O-coordinating ligands are described. The complexes have the form Pt(N^N^O-Ln)Cl (n = 1 to 20). The tridentate ligands comprise lateral pyridine and phenolate rings, offering the metal N and O coordination respectively, linked via an imine or hydrazone unit that provides a further, central N atom for coordination. The proligands HLn, some of which have previously been reported for the coordination of 1st row transition metal ions in other contexts, are Schiff bases that are readily synthesised by condensation of salicylaldehydes either with 8-aminoquinoline (to generate imine-based ligands HL1-4) or with 2-hydrazinopyridines (to generate hydrazone-based proligands HL5-20). The Pt(ii) complexes are prepared under mild conditions upon treatment of the proligands with simple Pt(ii) salts. Metathesis of the chloride ligand by an acetylide is possible, as exemplified by the preparation of two further complexes of the form Pt(N^N^O-Ln)(-C[triple bond, length as m-dash]C-Ar), where Ar = 3,5-bis(trifluoromethyl)phenyl. Nine of the complexes have been characterised in the solid state by X-ray diffraction. The imine-based complexes have intense low-energy absorption bands around 520 nm attributed to charge-transfer transitions. They display deep red phosphorescence in solution at ambient temperature, with λmax in the range 635-735 nm, quantum yields up to 4.6% and lifetimes in the microsecond range. The hydrazone complexes that feature a py-NH-N[double bond, length as m-dash]C-Ar linker display pH-dependent absorption spectra owing to the acidity of the hydrazone NH: these complexes have poor photostability in solution. In contrast, their N-methylated analogues (i.e., py-NMe-N[double bond, length as m-dash]C-Ar) show no evidence of photodecomposition. They are phosphorescent in solution at room temperature in the 600-640 nm region, the emission maximum being influenced by substituents in the phenolate ring. The results show how simply prepared tridentate Schiff base ligands - which offer the metal a combination of 5- and 6-membered chelate rings - can provide access to phosphorescent Pt(ii) complexes that have superior emissive properties to those of terpyridines, for example.

Two new homoleptic platinum(II) complexes are reported that feature aryl-appended 5-(2-pyridyl)-1,2,4- triazole chelates acting as N^N ligating ions, PtL1 2 and PtL2 2. Readily prepared from easily accessible proligands, they offer good solubility in organic solvents, allowing them to be incorporated into OLEDs through solution processing. Crystal structures reveal staggered, face-to-face packing of the p systems in adjacent complexes, but with no close PtPt interactions. The complexes display bright unimolecular phosphorescence: for PtL1 2 and PtL2 2 respectively, lmax = 502 and 514 nm; F = 0.21 and 0.48; t = 5.1 and 4.6 ms in deoxygenated CH2Cl2 at 295 K. Both complexes show a strong propensity to form intensely emissive excimers at higher concentrations: lmax = 585 and 625 nm for PtL1 2 and PtL2 2. The photophysical properties in doped and neat thin films have been investigated using steady-state and time-resolved methods. These studies highlight the presence of different environments of bimolecular excited states with different lifetimes, those emitting at lowest energy apparently having the longest lifetimes, contrary to what is normally found for unimolecular emitters through the effects of vibrational deactivation. The prototype solution-processed OLEDs gave EQEs of 9.6–12.5% for PtL1 2 and 8.8–11.4% for PtL2 2, impressive values for solution-processed devices incorporating such simple complexes and only a little inferior to the EQE of 15% achieved using PtL1 2 in a device prepared by evaporation. Compounds of this type have potential to provide the red and green components for white light OLEDs, due to their tunable, uni- and bimolecular excited state emission.

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.

BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response, however selective small molecule inhibitors of defined mechanism are currently lacking. Here we identify and characterise a specific inhibitor of BLM’s ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM.

Progress in the selective binding and detection of magnesium ions has been slower than other biologically important divalent metal ions like calcium and zinc. The most widely used ligands for Mg2+ are by no means optimal, as they are not selective for it. Nevertheless, Mg2+ is a major cation in all cells, with physiologically critical functions. There is a need for improved sensors for Mg2+. In this review, we consider how an appreciation of fundamental coordination chemistry principles may inform the development of new ligands for Mg2+. A number of representative examples of ligands of differing denticity are discussed in this context. Low-denticity ligands such as β-keto acids offer the best selectivities, but speciation is an issue as other polydentate ligands such as pyrophosphate may complete the coordination sphere. High-denticity ligands based on aminocarboxylates such as APTRA typically offer the highest stability constants, but they bind Ca2+ and Zn2+ more strongly than Mg2+. We highlight recent examples featuring related aminophosphinates, where the longer bonds and smaller bite angles favour selectivity towards Mg2+. Macrocyclic receptors for magnesium are not discussed explicitly.

Five Pt(II) complexes are described in which the metal ion is bound to anionic urn:x-wiley:14341948:media:ejic202000879:ejic202000879-math-0003 ‐coordinating ligands. The central, deprotonated N atom is derived from an imide Ar−C(=O)−NH−C(=O)−Ar {PtL1–2Cl; Ar=pyridine or pyrimidine}, an amide py−C(=O)−NH−CH2−py {PtL3Cl}, or a hydrazide py−C(=O)−NH−N=CH−py {PtL4Cl}. The imide complexes PtL1–2Cl show no significant emission in solution but are modestly bright green/yellow phosphors in the solid state. PtL3Cl is weakly phosphorescent. PtL4Cl is formed as a mixture of isomers, bound through either the amido or imino nitrogen, the latter converting to the former upon absorption of light. Remarkably, the imino form displays fluorescence in solution, λ0,0=535 nm, whereas the amido shows phosphorescence, λ0,0=624 nm, τ=440 ns. It is highly unusual for two isomeric compounds to display emission from states of different spin multiplicity. The amido‐bound PtL4Cl can act as a bidentate urn:x-wiley:14341948:media:ejic202000879:ejic202000879-math-0004 ‐coordinating ligand, demonstrated by the formation of bimetallic complexes with iridium(III) or ruthenium(II).

International audience; Enantiopure tris-helicenic chiral-at-iridium complexes have been prepared, constituting the first examples of organometallic metal-tris-helicenes. They have the mer- or fac-Ir(CC:)(3) form, where (CC:) is an N-heterocyclic carbene ligand N-substituted with a hexahelicene. Their triskelion geometry and stereochemistry have been thoroughly studied and assigned by NMR in combination with quantum-chemical modelling and by comparison with the X-ray structure of analogues. Thanks to their Ir(iii)-based multihelicenic architecture, the complexes display strong electronic circular dichroism and optical rotation along with long-lived yellow phosphorescence, involving circularly polarized emission with g(lum) factors around 10(-3).

Brightly emissive platinum(II) complexes (λemission,max = 607-612 nm) of the type RLPtCl are reported, where RL is a cyclometalated N∧C-∧N-coordinating ligand derived from 1,3-di(2-trifluoromethyl-4-phenanthridinyl)benzene (CF3LH) or 1,3-di(2-tert-butyl-4-phenanthridinyl)benzene (tBuLH). Metathesis of the chlorido ligand can be achieved under mild conditions, enabling isolation of ionic compounds with the formula [CF3LPtL']PF6 where L' = pyridine or (4-dimethylamino)pyridine (DMAP), as well as the charge-neutral species tBuLPt(C≡C─C6H4─tBu) (C≡C─C6H4─tBu = 4-tert-butylphenylacetylido). Compared with N∧N∧N-ligated Pt(II) complexes that form 5-membered chelates, these compounds all contain 6-membered rings. Expanding the chelate ring size from 5 to 6 has been previously demonstrated to enhance emission in some N∧N∧N-coordinated Pt(II) species─for example, in complexes of 2,6-di(8-quinolinyl)pyridine vs those of 2,2':6',2″-terpyridine─but in related N∧C-∧N-coordinated species, luminescence quantum yields are significantly lower for the 6-membered chelate ring complexes. Here, we demonstrate that site-selective benzannulation of the quinolinyl side-arms can offset the deleterious effect of changing the chelate ring-size and boost photophysical properties such as the quantum yield. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations suggest that benzannulation counterintuitively destabilizes the emissive triplet states compared to the smaller π-system, with the "imine-bridged biphenyl" form of the phenanthridinyl arm helping to buffer against larger molecular distortions, enhancing photoluminescence quantum yields up to 0.09 ± 0.02. The spontaneous formation under aerated conditions of a Pt(IV) derivative (CF3LPtCl3) is also reported, together with its molecular structure in the solid state.

A series of new red phosphors based on apatite-type gadolinium silicate host, Gd9.33−xEux(SiO4)6O2 (0.03 < x < 1.87), have been synthesised and analysed. The phosphors show excellent chemical and thermal stability, losing only 10% of their emission intensity at 150 °C (working LED temperature) relative to that at room temperature through the electric dipole–dipole interaction. They exhibit efficient Eu3+ narrow-band red emission (quantum yield up to 75%; full-width at half-maximum (FWHM) = 7 nm; CIE colour coordinates x = 0.65, y = 0.35) of exceptional colour purity (94.2%), and the host can be heavily doped with Eu3+ (up to 10 at%) without concentration quenching of the emission. Variable-temperature powder X-ray diffraction, photoluminescence spectroscopy and Judd–Ofelt analysis of the phosphors’ radiative properties reveal the favourable influence of the structural properties of the apatite-type host on the efficiency and thermal stability of the Eu3+-activated Gd9.33(SiO4)6O2 emission.

A synthetic methodology for accessing narrow-band, deep-red phosphorescence from mononuclear Pt(II) complexes is presented. These charge-neutral complexes have the general structure (N^N–^N)PtCl, in which the Pt(II) centers are supported by benzannulated diarylamido ligand scaffolds bearing substituted quinolinyl and/or phenanthridinyl arms. Emission maxima ranging from 683 to 745 nm are observed, with lifetimes spanning from 850 to 4500 ns. In contrast to the corresponding proligands, benzannulation is found to counterintuitively but markedly blue-shift emission from metal complexes with differing degrees of ligand benzannulation but similar substitution patterns. This effect can be further tuned by incorporation of electron-releasing (Me, tBu) or electron-withdrawing (CF3) substituents in either the phenanthridine 2-position or quinoline 6-position. Compared with symmetric bis(quinoline) and bis(phenanthridine) architectures, “mixed” ligands incorporating one quinoline and one phenanthridine unit present a degree of charge transfer between the N-heterocyclic arms that is more pronounced in the proligands than in the Pt(II) complexes. The impact of benzannulation and ring-substitution on the structure and photophysical properties of both the proligands and their deep-red emitting Pt(II) complexes is discussed.

We report an approach to rotaxanes in which the metal ion of a cyclometallated PtII luminophore is embedded in the space created by the mechanical bond. Our results show that the interlocked ligand environment stabilises a normally labile PtII–triazole bond against displacement by competing ligands and that the crowded environment of the mechanical bond retards oxidation of the PtII centre, without perturbing the photophysical properties of the complex. When an additional pyridyl binding site is included in the axle, the luminescence of the PtII centre is quenched, an effect that can be selectively reversed by the binding of AgI. Our results suggest that readily available interlocked metal-based phosphors can be designed to be stimuli responsive and have advantages as stabilised triplet harvesting dopants for device applications., We report an approach to interlocked PtII luminophores in which the mechanical bond stabilises the coordination environment of the embedded metal ion.

11 figures, 3 tables.-- This document is the Accepted Manuscript version of a Published Work that appeared in final form in Industrial and Engineering Chemistry Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.iecr.9b05835, Chemical-looping combustion (CLC) has been introduced as a promising technique with inherent advantages for efficient, low-cost CO2 separation. The type of oxygen carrier employed plays a vital role in improving the overall efficiency and economic penalty of the system. This study investigates the performance of a CuO oxygen carrier impregnated onto ZrO2 in a continuously operated 500 Wth CLC unit over 30 h of CH4 combustion. A decrease in combustion efficiency was observed during the initial 10 h followed by stabilization. A loss of CuO of between 13 and 5 wt % was recorded during the first 5 h of combustion before the CuO content was kept constant. This loss was due to the Cu layer peeling off the surface of particles and the clustering and migration of CuO from internal areas to the surface and then attrited. The effect of the oxygen carrier-to-fuel ratio (ϕ) on the combustion efficiency of the impregnated Cu-based oxygen carrier was studied. In order to reach a combustion efficiency of 99%, ϕ values of 3.9 were needed. The particle attrition rate was stabilized after 30 h of operation at 0.06%/h, and the estimated lifetime was 1500 h of operation. XRD and TPR analyses confirmed very low interaction between CuO and the support (ZrO2), which was unable to retain CuO inside the particles. Therefore, the lack of interaction between CuO and the ZrO2 support is not positive for oxygen carrier behavior in the CLC process., The work presented in this article is partially funded by the Spanish Research Council (CSIC) through the Intramural Project (201980E043) and by the European Commission Seventh Framework Programme under Grant 608571 (Project acronym SUCCESS). S. Toufigh Bararpour is grateful to Mitacs Globalink Research for the award received (Mitacs Globalink Research Award IT13491 for students studying in Canadian universities).

International audience; By attaching pyridine groups to a diaza[6]helicene, a helical, bis-ditopic, bis-N N-coordinating ligand can be accessed. Dinuclear rhenium complexes featuring this bridging ligand, of the form [{Re(CO) Cl} (N N-N N)], have been prepared and resolved to give enantiopure complexes. These complexes are phosphorescent in solution at room temperature under one- and two-photon excitation. Their experimental chiroptical properties (optical rotation, electronic circular dichroism and circularly polarized emission) have been measured. They show, for instance, emission dissymmetry factors of c.a. ±3x10 . Quantum-chemical calculations indicate the importance of stereochemistry on the optical activity, pointing towards further design improvements in such types of complexes.

A stochastic model is presented of two coupled fluidised-bed reactors with a steady circulation of particles between them. The particles undergo reaction in each fluidised bed. The model uniquely accounts for the full conversion history of particles as they are circulated. Chemical looping combustion (CLC) is an example of such a process. We have previously used the model, in a general form, to understand the sensitivity of a CLC process to factors such as the nature of the gas-solid reactions or the residence time distribution of the particles in the reactors. To demonstrate that the stochastic model is also valuable for simulating and optimising specific configurations of CLC, it is applied in this paper to simulate CLC with methane as the fuel gas, conducted in a laboratory-scale circulating fluidised bed. Under the operating conditions of the circulating fluidised bed, it was found that the oxidation and reduction reactions were limited by the intrinsic chemical kinetics of the oxygen carrier particles. It was possible to conduct experiments in a packed bed reactor for reduction and a thermogravimetric analyser for oxidation where the reaction was also limited by the intrinsic chemical kinetics. This enabled a single particle model, for inclusion in the stochastic model, to be developed independently of the experiments in the circulating fluidised bed. The resulting stochastic model was able to simulate the performance of the circulating fluidised bed with reasonable accuracy.

Platinum(II) complexes featuring conjugated aromatic ligands are widely studied in the context of luminescence. Many such compounds have been discovered that display intense phosphorescence from triplet excited states, offering potential applicability to numerous areas of contemporary interest, including as phosphors for light-emitting devices and imaging agents in cell biology. Aside from the large number of mononuclear Pt(II) complexes that have been reported in the context of luminescence, there are several examples of multinuclear systems – ones that incorporate two or more Pt(II) ions or Pt(II) in combination with other platinum group metal ions. The introduction of a second metal ion can lead to very different luminescence properties compared to the mononuclear analogues. This review aims to provide an overview of some of the key features of multinuclear Pt(II) complexes and their luminescence. It proves to be convenient to subdivide the examples into three classes, according to whether or not there are significant intramolecular interfacial interactions between the square-planar units. In some cases (Class A), for example with aromatic bridging ligands, the units are rigidly held apart from one another and no such intramolecular interactions are possible. In some such complexes, however, the presence of a second metal ion can nevertheless lead to very different properties compared to mononuclear analogues. In particular, recent work has shown that large red shifts in absorption and emission can be accompanied by an increase in the phosphorescence radiative rate constant, offering a way to efficient red and near-infrared emitters. In Class B, on the other hand, the planar Pt(II) units are rigidly held in a conformation that facilitates interfacial interactions. In many cases they involve overlap of Pt 5dz2 and 6pz orbitals, leading to the generation of low-energy 3MMLCT excited states similar to those seen in aggregates of mononuclear Pt(II) complexes. Finally, complexes in Class C – of which there are very many and we cover only a selection of examples – are those in which there is some flexibility in the linkers between the Pt(II) units. They may display dual emission both from excited states that resemble those of the isolated units, and from lower-energy excited states similar to aggregates or excimers, owing to the ability of the Pt(II) moieties to approach one another in the appropriate conformation.

1,8-Bis(2-pyridyl)anthracene HL2 is shown to act as a tridentate, N^C^N-coordinating ligand to platinum(II), undergoing metallation at position 9 of the anthracene. The structures of Pt(N^C^N-L2)Cl and of HL2 have been determined by X-ray diffraction. The complex features two 6-membered chelate rings and an N-Pt-N bite angle of 178.16(7)°, close to the “ideal” value of 180°. The attainment of this angle necessitates not only a twisting of the pyridyl rings relative to the anthracene, but also a remarkable twisting distortion of the anthracene unit itself. The complex is isomeric with the previously reported Pt(d8qb)Cl {d8qb = 1,3-di(8-quinolyl)benzene}. A new derivative of the latter has been prepared, PtL3Cl, featuring methyl substituents in the central benzene ring ortho to the quinolines. Like PtL2Cl, its structure shows twisting of the coordinated heterocycles relative to the plane of the central aromatic ring. The Pt(II) complex PtL1Cl of a related N^C^N-coordinating ligand featuring extended conjugation, benzo[1,2-h: 5,4 = h’]diquinoline HL1, has also been prepared following a previously described procedure. PtL1Cl is brightly phosphorescent in deoxygenated solution at ambient temperature, in the red region of the spectrum. The impressive photoluminescence quantum yield of 0.30 and long emission lifetime of 38 μs are indicative of a rigid structure with little excited state distortion. In contrast, PtL2Cl shows no detectable emission, probably due to the distorted nature of the structure leading to rapid non-radiative decay of the excited state. This result contrasts with the weak red emission displayed by the isomeric Pt(d8qb)Cl and its dimethylated derivative PtL3Cl.

The development of a route applicable to the preparation of acyclic glutamic acid-based chelating ligands bearing two different auxiliary donor groups linked to the nitrogen atom by methylene spacers is described and applied to the synthesis of the new polydentate ligand HBGl3, the first example of such a structure. The synthesis is accomplished using a strategy employing reductive amination and t-butyl ester protected intermediates. The most basic pKa values for the HBGl3 ligand have been estimated via potentiometric and UV–Visible titration techniques.

The generation of multimetallic assemblies is a widely explored theme, owing to the relevance of controlling energy and electron transfer between metal centres to many fields of contemporary importance. Boronic acid substituted coordination and organometallic complexes have been shown to be useful synthons in the formation of such structures through cross-coupling with halogenated complexes. In this work we used such a methodology to generate an octanuclear mixed-metal compound of composition Ir7Ru having a dendrimer wedge-like structure. The method combined cross-coupling with regiospecific bromination of phenylpyridine (ppy) ligands at the position para to the C–Ir bond. The propensity of Ir(ppy)2-based complexes to electrophilic bromination was found to be deactivated by the introduction of fluorine atoms. The coupling methodology was extended to rhodium-containing systems, exemplified by a tetranuclear system of composition Rh2Ir1Ru1. The synthesis required the use of boronic acid appended RhIII complexes, which could be accessed by the introduction of a neopentyl boronate ester appended bipyridine into the coordination sphere of RhIII. The excited-state energies of the constituent metal units in the resulting multinuclear complexes are such that unidirectional energy transfer occurs from the RhIII/IrIII branches to the RuII core. The luminescence thus resembles that of an isolated [Ru(bpy)3]2+ unit, but the ability of the structure to collect light is greatly enhanced.

1. AFQ056 phenotyping results indicate that CYP1A1 is responsible for the formation of the oxidative metabolite, M3. In line with the predominant assumption that CYP1A1 is mainly expressed in extrahepatic tissues, only traces of M3 were detected in hepatic systems. The aim of this study was to investigate the pulmonary CYP1A1 mediated metabolism of AFQ056 in rat.2. Western blot analysis confirmed that CYP1A1 is expressed in rat lung albeit at low levels. M3 formation was clearly observed in recombinant rat CYP1A1, lung microsomes and lung tissue slices and was strongly inhibited by ketoconazole in the incubations. As CYP3A4 and CYP2C9 metabolites were only observed at trace levels, we concluded that the reduced M3 formation was due to CYP1A1 inhibition.3. AFQ056 lung clearance (CLlung) as estimated from in vitro data was predicted to be negligible (

EDTA is a powerful, cheap and widely-used chelating unit for a large range of metal ions. To link it covalently to other molecules, the formation of an amide bond using one of the carboxylates is an attractive and simple approach, even though it may compromise metal ion binding as one of the four carboxylate donors is lost. Here we undertake a quantitative study of the metal ion binding of two new mono-amide derivatives of EDTA, namely AmGly1 and AmPy1, featuring an additional coordinating carboxylate or pyridyl group in the amide, respectively. The compounds are conveniently synthesised through alkylation of the tris-t-butyl ester of ethylenediamine-triacetic acid with the appropriate α-chloroamide. The switch from carboxylate to amide is found to impact Fe3+ binding the most amongst the metal ions examined (Mg2+, Ca2+, Mn2+, Fe3+, Zn2+), with a drop in log K(ML) of around 10 units in aqueous solution. The affinities for the other metals are less severely affected. Nevertheless, at the physiologically relevant pH of 7.4, their ability to bind Fe3+ is only reduced by around 6 log units when pFe3+ is considered (where [L]:[Fe3+] = 10:1). AmGly1 forms a dinuclear Ca2+ complex which has been characterised crystallographically. It is a C2-symmetric 2:2 complex featuring a dicapped octahedral coordination geometry around Ca2+. In the crystal, the Ca2(AmGly1)2 units are linked via hydrated Na+ ions coordinated by a number of the oxygen atoms, including the pendent carboxylate.

Drug metabolism studies are performed in drug discovery to identify metabolic soft spots, detect potentially toxic or reactive metabolites and provide an early insight into potential species differences. The relative peak area approach is often used to semi-quantitatively estimate the abundance of metabolites. Differences in the liquid chromatography-mass spectrometry responses result in an underestimation or overestimation of the metabolite and misinterpretation of results. The relative MS response factors (RF) of 132 structurally diverse drug candidates and their 233 corresponding metabolites were evaluated using a capillary-liquid chromatography/high-resolution mass spectrometry system. All of the synthesized metabolites discussed here were previously identified as key biotransformation products in discovery investigations or predicted to be formed. The most commonly occurring biotransformation mechanisms such as oxygenation, dealkylation and amide cleavage are represented within this dataset. However, relatively few phase II metabolites were evaluated because of the limited availability of authentic standards. Approximately 85% of these metabolites had a relative RF in the range between 0.2 (fivefold under-prediction) and 2.0 (twofold over-prediction), and the median MS RF was 0.6. Exceptions to this included very small metabolites that were hardly detectable. Additional experiments performed to understand the impact of the MS platform, flow rate and concentration suggested that these parameters do not have a significant impact on the RF of the compounds tested. This indicates that the use of relative peak areas to semi-quantitatively estimate the abundance of metabolites is justified in the drug discovery setting in order to guide medicinal chemistry efforts. Copyright © 2017 John Wiley & Sons, Ltd.

In a macrocyclic terbium complex incorporating a biaryl sensitiser, the observed variation of emission lifetime is shown to be determined by the solubility of oxygen in the solvent system and the relative energy of the chromophore excited state, rather than any dependence on solvent viscosity.

International audience; A new enantiopure cyclometallated iridium complex bearing a [4]helicenic C perpendicular to C--coordinating and two N perpendicular to C--coordinating dfppy (2-(2,4-difluorophenyl)-pyridyl) ligands was prepared. This complex displayed long-lived phosphorescence both in solution and in the solid state. Its chiroptical properties, namely electronic circular dichroism and circularly polarized luminescence, were also examined. Comparison with former chiral complexes enabled assignment of the Delta(Ir)-(-) and ? (Ir)-(+) absolute configurations.

The structural and photophysical properties of three sets of luminescent copper complexes of the form [(P^N)2Cu]X are presented. Here, P^N represents a bidentate ligand based on phenanthridine (3,4-benzoquinoline) incorporating a phosphine unit at the 4-position, of which three examples are investigated, namely 4-(diphenylphosphino)phenanthridine (L1), 4-(diphenylphosphino)-2-methylphenanthridine (L2) and 2,6-dimethyl-4-(diphenylphosphino)phenanthridine (L3). For each P^N-coordinating ligand, the corresponding homoleptic copper(I) complex (1X, 2X, 3X) has been prepared as both the hexafluorophosphate and tetraphenylborate salt (X = PF6− or BPh4−). The identity of the counterion has a profound and unexpected impact on the emission properties of the powder samples – but only for complexes of ligands bearing methyl substituents close to the metal (3X). The synergistic effect of combining inter-ion interactions and ligand design enables emission tuning from orange to yellow, in the opposite (hypsochromic) direction compared to employing either strategy on its own. These effects can be attributed to differences in molecular packing, in particular to the combined impact of ligand structure and inter-ionic interactions on distortions in the excited state relative to the ground state. The results have been interpreted with the help of density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations.

Cyclometallated Pt(II) complexes with arylpolypyridyl ligands have impressive photophysical properties (high quantum yields, long lifetimes and tuneable emission) which can be readily tuned by modification of the organic ligand. Despite this, few examples of cyclometallated Pt(II) complexes as sensitisers for Ln(III) emission have been reported. Herein, we report the photophysical properties for a series of bimetallic complexes incorporating an N^C^N-coordinated Pt(II) bearing an alkynyl terpyridine as a metalloligand for a Ln(III) ion (where Ln = Nd, Gd, Er, Yb and Lu). Using a combination of steady state, time-resolved, and transient absorption experiments, the influence on the photophysical properties of the metalloligand exerted by the different Ln(III) cations has been investigated, together with the energy transfer efficiency from the metalloligand to the Ln(III) 4f* excited state.

© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/, One of the most important current objectives of the Chemical Looping Combustion (CLC) technology for gaseous fuels lies in scaling-up the aforementioned technology in the short term from 100 kWth to 10 MWth scale. In order to meet this challenge, the commercial availability of suitable multi ton-scale oxygen carrier materials at competitive price is needed. In this work, a Cu-based oxygen carrier prepared by the impregnation method using a commercial alumina as support, referred as Cu14γAl_Commercial, has been developed and evaluated in a 500 Wth CLC pilot plant during the combustion of CH4 at two different temperatures, i.e., 800 °C and 900 °C. The outstanding results obtained in terms of both combustion efficiency and mechanical stability have shown that the Cu14γAl_Commercial impregnated oxygen carrier can be selected to upscale CLC technology for gaseous fuels., The work presented in this article is partially funded by the Spanish Ministry of Economy and Competitiveness (ENE 2014-56857-R), by the European Regional Development Fund (ERDF), and by the European Commission Seventh Framework Programme under the grant agreement No. 608571 (Project acronym SUCCESS). A. Abad and A. Cabello thank CSIC for the financial support given to the project 201480E101.

The diacylglycerol lipases (DAGLα and DAGLβ) hydrolyse DAG to generate 2-arachidonoylglycerol (2-AG), the principal endocannabinoid and main precursor of arachidonic acid (AA). The DAGLs make distinct tissue specific contributions towards 2-AG and AA levels and therefore selective modulators for these enzymes could play crucial roles towards harnessing their therapeutic potential. Relatively high-throughput assays have recently been reported for DAGLα and have proven useful towards the characterization of inhibitors of this enzyme. Similar assays are also warranted for DAGLβ which was the aim of this study. We first adapted previously reported DAGLα membrane assays (using PNPB and DiFMUO as substrates) to measure recombinant DAGLβ activity in membranes. In contrast to results with DAGLα, both substrates provided a relatively limited signal window for measuring DAGLβ activity, however, an improved window was obtained when employing a third commercially available substrate, EnzChek. In order to further improve on the assay parameters, we successfully purified the glutathione S-transferase (GST) tagged catalytic domain of DAGLβ. Activity of the enzyme was confirmed using EnzChek as well as two DAGL inhibitors (THL and OMDM-188). The purified DAGLβ catalytic domain assay described here provides the basis for a relatively clean and convenient assay with the potential to be adapted for high-throughput drug discovery efforts.

International audience; Monometallic gold(I)-alkynyl-helicene complexes (1a,b,) and bimetallic gold(I)-alkynyl-helicene architectures featuring the presence (2a,b) or absence (3a,b) of aurophillic intramolecular interactions were prepared by using different types of phosphole ligands (mono-phosphole L1 or bis-phospholes L2,3). The influence of the Au(I) d10-metal center(s) on the electronic, photophysical and chiroptical properties of these unprecedented phosphole-gold(I)-alkynyl-helicene complexes were examined. Experimental and theoretical results highlight the importance of ligand-to-ligand-type charge transfers and the strong effect of presence or absence of Au(I)-Au(I) interactions in 2a,b.