Photoluminescence of Platinum(II) Complexes with Diazine-Based Ligands.

In the last past twenty years, research on luminescent platinum (II) complexes has been intensively developed for useful application such as organic light emitting diodes (OLEDs). More recently, new photoluminescent complexes based on diazine ligands (pyrimidine, pyrazine, pyridazine, quinazoline and quinoxaline) have been developed in this context. This review will summarize the photophysical properties of most of the phosphorescent diazine Pt(II) complexes described in the literature and compare the results to pyridine analogues whenever possible. Based on the emission color, and the photoluminescence quantum yield (PLQY) values, the relationship between structure modification, and photophysical properties are highlighted. Tuning of emission color, quantum yields in solution and solid state and, for some complexes, aggregation induced emission (AIE) or thermally activated delayed fluorescence (TADF) properties are described. When emitting OLEDs have been built from diazine Pt(II) complexes, the external quantum efficiency (EQE) values and luminance for different emission wavelengths and in some cases, chromaticity coordinates obtained from devices, are given. Finally, this review highlights the growing interest in studies of new luminescent diazine Pt(II) complexes for OLED applications.

Trapping of Terminal Platinapolyynes by Copper(I) Catalyzed Click Cycloadditions; Probes of Labile Intermediates in Syntheses of Complexes with Extended sp Carbon Chains, and Crystallographic Studies.

The silylated hexatriynyl complex trans-(C6 F5 )(p-tol3 P)2 Pt(C≡C)3 SiEt3 (PtC6 TES) is converted in situ to PtC6 H (wet n-Bu4 N+ F- , THF) and cross coupled with the diyne H(C≡C)2 SiEt3 (HC4 TES; CuCl/TMEDA, O2 ) to give PtC10 TES (71 %). This sequence is repeated twice to afford PtC14 TES (65 %) and then PtC18 TES (27 %). An analogous series of reactions starting with PtC8 TES gives PtC12 TES (60 %), then PtC16 TES (43 %), and then PtC20 TES (17 %). Similar cross couplings with H(C≡C)2 Si(i-Pr)3 (HC4 TIPS) give PtC12 TIPS (68 %), PtC14 TIPS (68 %), and PtC16 TIPS (34 %). The trialkylsilyl species (up to PtC18 TES) are converted to 3+2 "click" cycloadducts or 1,4-disubstituted 1,2,3-triazoles trans-(C6 F5 )(p-tol3 P)2 Pt(C≡C)n-1 C=CHN(CH2 C6 H5 )N=N (29-92 % after workups). The most general procedure involves generating the terminal polyynes PtCx H (wet n-Bu4 N+ F- , THF) in the presence of benzyl azide in DMF and aqueous CuSO4 /ascorbic acid. All of the preceding complexes are crystallographically characterized and the structural and spectroscopic properties analyzed as a function of chain length. Two pseudopolymorphs of PtC20 TES are obtained, both of which feature molecules with parallel sp carbon chains in a pairwise head/tail packing motif with extensive sp/sp van der Waals contacts.

Accuracy of saliva and nasopharyngeal sampling for detection of SARS-CoV-2 in community screening: a multicentric cohort study.

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France. Two nasopharyngeal swabs and one saliva sample were simultaneously collected. Diagnostic accuracies of nasopharyngeal Ag testing and of three saliva NAAT methods were assessed as compared to nasopharyngeal NAAT. A total of 1452 ambulatory children and adults were included. Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was 94%, 23%, 96%, and 94% for the three different protocols of saliva NAAT and for the nasopharyngeal Ag test, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT is similar to that of nasopharyngeal NAAT, subject to compliance with specific protocols for saliva. Registration number: NCT04578509.

Reduction of Nitrogen Oxides by Hydrogen with Rhodium(I)-Platinum(II) Olefin Complexes as Catalysts.

The nitrogen oxides NO2 , NO, and N2 O are among the most potent air pollutants of the 21st century. A bimetallic RhI -PtII complex containing an especially designed multidentate phosphine olefin ligand is capable of catalytically detoxifying these nitrogen oxides in the presence of hydrogen to form water and dinitrogen as benign products. The catalytic reactions were performed at room temperature and low pressures (3-4 bar for combined nitrogen oxides and hydrogen gases). A turnover number (TON) of 587 for the reduction of nitrous oxide (N2 O) to water and N2 was recorded, making these RhI -PtII complexes the best homogeneous catalysts for this reaction to date. Lower TONs were achieved in the conversion of nitric oxide (NO, TON=38) or nitrogen dioxide (NO2 , TON of 8). These unprecedented homogeneously catalyzed hydrogenation reactions of NOx were investigated by a combination of multinuclear NMR techniques and DFT calculations, which provide insight into a possible reaction mechanism. The hydrogenation of NO2 proceeds stepwise, to first give NO and H2 O, followed by the generation of N2 O and H2 O, which is then further converted to N2 and H2 O. The nitrogen-nitrogen bond-forming step takes place in the conversion from NO to N2 O and involves reductive dimerization of NO at a rhodium center to give a hyponitrite (N2 O2 2- ) complex, which was detected as an intermediate.

Urinary Exosomes of Patients with Cystic Fibrosis Unravel CFTR-Related Renal Disease.

Background: The prevalence of chronic kidney disease is increased in patients with cystic fibrosis (CF). The study of urinary exosomal proteins might provide insight into the pathophysiology of CF kidney disease. Methods: Urine samples were collected from 19 CF patients (among those 7 were treated by cystic fibrosis transmembrane conductance regulator (CFTR) modulators), and 8 healthy subjects. Urine exosomal protein content was determined by high resolution mass spectrometry. Results: A heatmap of the differentially expressed proteins in urinary exosomes showed a clear separation between control and CF patients. Seventeen proteins were upregulated in CF patients (including epidermal growth factor receptor (EGFR); proteasome subunit beta type-6, transglutaminases, caspase 14) and 118 were downregulated (including glutathione S-transferases, superoxide dismutase, klotho, endosomal sorting complex required for transport, and matrisome proteins). Gene set enrichment analysis revealed 20 gene sets upregulated and 74 downregulated. Treatment with CFTR modulators yielded no significant modification of the proteomic content. These results highlight that CF kidney cells adapt to the CFTR defect by upregulating proteasome activity and that autophagy and endosomal targeting are impaired. Increased expression of EGFR and decreased expression of klotho and matrisome might play a central role in this CF kidney signature by inducing oxidation, inflammation, accelerated senescence, and abnormal tissue repair. Conclusions: Our study unravels novel insights into consequences of CFTR dysfunction in the urinary tract, some of which may have clinical and therapeutic implications.

Syntheses, Structures, and Spectroscopic Properties of 1,10-Phenanthroline-Based Macrocycles Threaded by PtC8 Pt, PtC12 Pt, and PtC16 Pt Axles: Metal-Capped Rotaxanes as Insulated Molecular Wires.

The platinum polyynyl complexes trans-(C6 F5 )(p-tol3 P)2 Pt(C≡C)n/2 H undergo oxidative homocoupling (O2 , CuCl/TMEDA) to diplatinum polyynediyl complexes trans, trans-(C6 F5 )(p-tol3 P)2 Pt(C≡C)n Pt(Pp-tol3 )2 (C6 F5 ) (n=4, 2; 6, 5; 8, 8; 92-97 %) as reported previously. When related reactions are conducted in the presence of CuI adducts of the 1,10-phenanthroline-based macrocycles 2,9-(1,10-phenanthrolinediyl)(p-C6 H4 O(CH2 )6 O)2 (1,3-C6 H4 ) (10, 33-membered) or 2,9-(1,10-phenanthrolinediyl)(p-C6 H4 O(CH2 )6 O)2 (2,7-naphthalenediyl) (11, 35-membered), excess K2 CO3 , and I2 (oxidant), rotaxanes are isolated that feature a Pt(C≡C)n Pt axle that has been threaded through the macrocycle (2⋅10, 9 %; 5⋅10, 41 %; 5⋅11, 28 %; 8⋅10, 12 %; 8⋅11, 9 %). Their crystal structures are determined and analyzed in detail, particularly with respect to geometric perturbations and the degree of steric sp carbon chain insulation. NMR spectra show a number of shielding effects. UV/Vis spectra do not indicate significant electronic interactions between the Pt(C≡C)n Pt axles and macrocycles, although cyclic voltammetry data suggest rapid reactions following oxidation.

Cystatin C prevents neuronal loss and behavioral deficits via the endosomal pathway in a mouse model of down syndrome.

Cystatin C (CysC) plays diverse protective roles under conditions of neuronal challenge. We investigated whether CysC protects from trisomy-induced pathologies in a mouse model of Down syndrome (DS), the most common cause of developmental cognitive and behavioral impairments in humans. We have previously shown that the segmental trisomy mouse model, Ts[Rb(12.1716)]2Cje (Ts2) has DS-like neuronal and behavioral deficiencies. The current study reveals that transgene-mediated low levels of human CysC overexpression has a preventive effect on numerous neuropathologies in the brains of Ts2 mice, including reducing early and late endosome enlargement in cortical neurons and decreasing loss of basal forebrain cholinergic neurons (BFCNs). Consistent with these cellular benefits, behavioral dysfunctions were also prevented, including deficits in nesting behavior and spatial memory. We determined that the CysC-induced neuroprotective mechanism involves activation of the phosphotidylinositol kinase (PI3K)/AKT pathway. Activating this pathway leads to enhanced clearance of accumulated endosomal substrates, protecting cells from DS-mediated dysfunctions in the endosomal system and, for BFCNs, from neurodegeneration. Our findings suggest that modulation of the PI3/AKT pathway offers novel therapeutic interventions for patients with DS.

Reversible Redox Switching of Chromophoric Phenylmethylenepyrans by Carbon-Carbon Bond Making/Breaking.

Electrochromic organic systems that can undergo substantial variation of their optical properties upon electron stimulus are of high interest for the development of functional materials. In particular, devices based on radical dimerization are appropriate because of the effectiveness and speed of carbon-carbon bond making/breaking. Phenylmethylenepyrans are organic chromophores which are well suited for such purposes since their oxidation leads to the reversible formation of bispyrylium species by radical dimerization. In this paper, we show that the redox and spectroscopic properties of phenylmethylenepyrans can be modulated by adequate variation of the substituting group on the para position of the phenyl moiety, as supported by DFT calculations. This redox switching is reversible over several cycles and is accompanied by a significant modification of the UV-vis spectrum of the chromophore, as shown by time-resolved spectroelectrochemistry in thin-layer conditions.

Adsorption of single 1,8-octanedithiol molecules on Cu(100).

Single 1,8-octanedithiol (ODT) molecules adsorbed onto the Cu(100) surface have been characterized by using scanning tunneling microscopy (STM) and studied by semi-empirical calculations. STM images have revealed two types of chiral molecules on the surface upon adsorption and both types of molecules showed two bright spots at the extremities of a small rod due to the enhanced electronic density contrast of the chemisorbed sulfur atoms. In sub-monolayer regime deposition, ODT molecules exhibit preferential adsorption directions and the relaxation mechanism is driven by the chemisorption of the two sulfur atoms in a hollow site of the surface. By means of calculations several conformations of the molecule according to the energetically favorable alkane body stretching constraint have been studied. The comparison between relaxed conformations and between calculated and experimental STM images, followed by an analysis of different orientations, has allowed determining unambiguously the most favorable position of the ODT molecule on Cu(100).

Cryptocephal, the Drosophila melanogaster ATF4, is a specific coactivator for ecdysone receptor isoform B2.

The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (USP). In Drosophila melanogaster, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s) contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4) is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC), the Drosophila homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH), an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.

Seeding molecular rotators on a passivated silicon surface.

Thermally activated rotation of single molecules adsorbed on a silicon-based surface between 77 and 150 K has been successfully achieved. This remarkable phenomenon relies on a nanoporous supramolecular network, which acts as a template to seed periodic molecule rotors on the surface. Thermal activation of rotation has been demonstrated by STM experiments and confirmed by theoretical calculations.

Exploring structural and optical properties of a new series of soft salts based on cyclometalated platinum complexes.

A series of nine new soft salts based on two platinum(II) complexes, namely ([Pt(C^N)(CN)2]-[Pt(C^N)(en)]+) (en = ethane-1,2-diamine), has been developed and synthesized. Their photophysical properties in both solution and the solid state were described. All soft salt complexes exhibit phosphorescence emission with PLQY in the solid state up to 0.36. Most of these materials displayed aggregation-induced emission (AIE) or aggregation-induced emission enhancement (AIEE) in water/DMSO solutions as the water ratio increased. Structure-property relationships were analyzed in relation to emission properties. The presence of the free nitrogen atoms in soft salt complexes with a C^N pyrimidine-based ligand allowed for reversible sensitivity to acidic vapors, resulting in the quenching of phosphorescence emission. Additionally, for selected soft salts, we described reversible vapochromism behaviour, making these new materials interesting for multi-detection purposes in anti-counterfeiting applications.

The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space.

In vitro studies have shown that neuronal cell cultures secrete exosomes containing amyloid-ß precursor protein (APP) and the APP-processing products, C-terminal fragments (CTFs) and amyloid-ß (Aß). We investigated the secretion of full-length APP (flAPP) and APP CTFs via the exosome secretory pathway in vivo. To this end, we developed a novel protocol designed to isolate exosomes secreted into mouse brain extracellular space. Exosomes with typical morphology were isolated from freshly removed mouse brains and from frozen mouse and human brain tissues, demonstrating that exosomes can be isolated from post-mortem tissue frozen for long periods of time. flAPP, APP CTFs, and enzymes that cleave both flAPP and APP CTFs were identified in brain exosomes. Although higher levels of both flAPP and APP CTFs were observed in exosomes isolated from the brains of transgenic mice overexpressing human APP (Tg2576) compared with wild-type control mice, there was no difference in the number of secreted brain exosomes. These data indicate that the levels of flAPP and APP CTFs associated with exosomes mirror the cellular levels of flAPP and APP CTFs. Interestingly, exosomes isolated from the brains of both Tg2576 and wild-type mice are enriched with APP CTFs relative to flAPP. Thus, we hypothesize that the exosome secretory pathway plays a pleiotropic role in the brain: exosome secretion is beneficial to the cell, acting as a specific releasing system of neurotoxic APP CTFs and Aß, but the secretion of exosomes enriched with APP CTFs, neurotoxic proteins that are also a source of secreted Aß, is harmful to the brain.

Phosphorescent cyclometalated platinum(II) complexes with phenyldiazine N

A series of phosphorescent platinum(II) complexes containing various phenyldiazine-type bidentate N^C ligands have been successfully synthesized and characterized. Structural modifications have been made to bidentate cyclometalating ligands regarding the nature of the diazine ring (pyrimidine, pyrazine and quinazoline), the substituent groups at the C4 position of the pyrimidine ring (OCH3, CF3) and the EDGs at the para position of the Pt atom (OCH3, Ph, NPh2, carbazol). In addition, the electronic properties of the azaheterocyclic ancillary ligand have been modulated in this series of complexes (pyridine, 4-methoxy-pyridine or pyrimidine). X-ray diffraction studies have been performed on three complexes, revealing Pt(II) ions in a distorted square-planar geometrical environment with no Pt(II)⋯Pt(II) interactions but with moderate π-π interactions in the solid-state structure. Electrochemical and computational studies suggest a ligand-centered reduction on the diazine ligands with, in some cases, additional contribution from the azaheterocyclic ancillary ligand, whereas oxidation occurs on the Pt-phenyl ring substituent moieties. All complexes exhibit phosphorescence emission ranging from green to red/near-infrared, both in solution and in the solid state. Complexes bearing a 2-(3-methoxyphenyl)pyrimidine ligand show the best PLQY of the series, up to 52% in a CH2Cl2 solution and 20% in the solid state. Furthermore, the solid state PLQY of one of the near-infrared emitting phenylquinazoline complex has been found to be 6%.

Luminescent cyclometalated alkynylplatinum(II) complexes with 1,3-di(pyrimidin-2-yl)benzene ligands: synthesis, electrochemistry, photophysics and computational studies.

In this article, we report on a series of cyclometalated chloro- and alkynyl-platinum(II) complexes bearing various tridentate N^C^N-cyclometalated ligands derived from 1,3-bis(pyrimidin-2-yl)benzene. The X-ray crystal structures of two alkynyl-platinum(II) complexes were determined and other structures were DFT-calculated. Electrochemical and DFT-computational studies suggest a ligand-centred reduction on the R1-substituted N^C^N ligand, whereas oxidation likely occurs either on the Pt-phenylacetylide moiety and/or the cyclometalated ligand. In CH2Cl2 solution at room temperature, the complexes show phosphorescent emissions ranging from green to orange, depending on the R1 and R2 substituents on the ligands. In KBr solid state matrix, excluding complexes bearing a trifluoromethyl substituted ligand, all compounds exhibit red emission. The presence of an alkynyl ancillary ligand has limited influence on absorption and emission spectra except in the case of the complex with the strongly electron-donating diphenylamino R2 substituent on the alkynyl ligand, for which a significant red-shift was observed. The alkynyl Pt(II) complex with OMe groups as both R1 and R2 substituents shows the best emission quantum yield (0.81 in CH2Cl2 solution) in this series. The full series of DFT calculated band gaps correlated generally well with the electrochemical and absorption data and reasonably model the impact of the substituents on the electronics of these complexes.

Controlling the charge state of a single redox molecular switch.

Scanning tunneling microscopy and dynamic force microscopy in the noncontact mode are used in combination to investigate the reversible switching between two stable states of a copper complex adsorbed on a NaCl bilayer grown on Cu(111). The molecular conformation in these two states is deduced from scanning tunneling microscopy imaging, while their charge is characterized by the direct measurement of the tip-molecule electrostatic force. These measurements demonstrate that the molecular bistability is achieved through a charge-induced rearrangement of the coordination sphere of the metal complex, qualifying this system as a new electromechanical single-molecular switch.

Investigation of second-order nonlinear optical responses in a series of V-shaped binuclear platinum(ii) complexes.

A series of four D-(π-Pt-π-A)2 new V-shaped binuclear platinum(ii) complexes bearing a diphenylpyranylidene ligand as a pro-aromatic donor group (D) and various electron-attracting groups (A) separated by platinum bis-acetylide fragments have been synthesized, characterized and studied for their electrochemical, photophysical and second-order nonlinear optical (NLO) properties. The nonlinear optical properties of these complexes have been determined by using the Electric-Field-Induced Second Harmonic (EFISH) generation technique, and their optical properties have been rationalized by Time-Dependent Density Functional Theory (TD-DFT) calculations relying on a range-separated hybrid. All complexes display positive µß0 values. In addition, the second-order NLO responses of the complexes could be easily modulated by incorporating various end-capped electron-attracting groups, namely malononitrile, indane-1,3-dione, pyrimidine and pyrimidinium. Remarkably, complex 7 bearing a pyrimidinium fragment displays the highest µß0 value among all the complexes of this series. Its NLO response is twice as high as that of the mononuclear analogue complex RD2, which has been confirmed both experimentally and theoretically.

Co-regulation of yeast purine and phosphate pathways in response to adenylic nucleotide variations.

Adenylate kinase (Adk1p) is a pivotal enzyme in both energetic and adenylic nucleotide metabolisms. In this paper, using a transcriptomic analysis, we show that the lack of Adk1p strongly induced expression of the PHO and ADE genes involved in phosphate utilization and AMP de novo biosynthesis respectively. Isolation and characterization of adk1 point mutants affecting PHO5 expression revealed that all these mutations also severely affected Adk1p catalytic activity, as well as PHO84 and ADE1 transcription. Furthermore, overexpression of distantly related enzymes such as human adenylate kinase or yeast UMP kinase was sufficient to restore regulation. These results demonstrate that adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways. We also establish that adk1 deletion and purine limitation have similar effects on both adenylic nucleotide pool and PHO84 or ADE17 expression. Finally, we show that, in the adk1 mutant, upregulation of ADE1 depends on synthesis of the previously described effector(s) (S)AICAR ((N-succinyl)-5-aminoimidazol-4-carboxamide ribotide), while upregulation of PHO84 necessitates the Spl2p positive regulator. This work reveals that adenylic nucleotide availability is a key signal used by yeast to co-ordinate phosphate utilization and purine synthesis.

A Drosophila gain-of-function screen for candidate genes involved in steroid-dependent neuroendocrine cell remodeling.

The normal functioning of neuroendocrine systems requires that many neuropeptidergic cells change, to alter transmitter identity and concentration, electrical properties, and cellular morphology in response to hormonal cues. During insect metamorphosis, a pulse of circulating steroids, ecdysteroids, governs the dramatic remodeling of larval neurons to serve adult-specific functions. To identify molecular mechanisms underlying metamorphic remodeling, we conducted a neuropeptidergic cell-targeted, gain-of-function genetic screen. We screened 6097 lines. Each line permitted Gal4-regulated transcription of flanking genes. A total of 58 lines, representing 51 loci, showed defects in neuropeptide-mediated developmental transitions (ecdysis or wing expansion) when crossed to the panneuropeptidergic Gal4 driver, 386Y-Gal4. In a secondary screen, we found 29 loci that produced wing expansion defects when crossed to a crustacean cardioactive peptide (CCAP)/bursicon neuron-specific Gal4 driver. At least 14 loci disrupted the formation or maintenance of adult-specific CCAP/bursicon cell projections during metamorphosis. These include components of the insulin and epidermal growth factor signaling pathways, an ecdysteroid-response gene, cabut, and an ubiquitin-specific protease gene, fat facets, with known functions in neuronal development. Several additional genes, including three micro-RNA loci and two factors related to signaling by Myb-like proto-oncogenes, have not previously been implicated in steroid signaling or neuronal remodeling.

Self-assembly of fivefold-symmetric molecules on a threefold-symmetric surface.

Buckybowls: The adsorption of penta-tert-butylcorannulene, a molecule with fivefold symmetry, on Cu(111), a surface with threefold symmetry, is investigated by scanning tunneling microscopy complemented by structure calculations. The symmetry mismatch is resolved by the formation of threefold-symmetric subunits consisting of three molecules, which combine with single molecules to form a nearly perfect filling of the plane (see picture).