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A new palladium-catalyzed domino approach for the synthesis of attractive spirocyclic indolines and dihydrobenzofurans was developed. The reaction proceeds through a sequential intramolecular Heck spirocyclization, remote C-H activation, and diazocarbonyl carbene insertion. Various spiroindolines and spirodihydrobenzofurans containing two quartenary carbon stereocenters were readily obtained in good to excellent yields. A preliminary study of asymmetric spirocyclization using chiral monophosphoramidite as a ligand was also conducted, enabling access to highly valuable chiral spiroindolines with up to 80% ee. [ABSTRACT FROM AUTHOR]

Chiral propargyl amides are particularly useful structural units in organic synthesis. The enantioselective synthesis of propargyl amide is highly desirable. Conventional approach involves the use of a stoichiometric amount of metal reagent or chiral auxiliary. In comparison, direct alkynylation with terminal alkyne is attractive because it avoids the use of stoichiometric organometallic reagent. The asymmetric coupling of aldehyde, amine, and alkyne (A3-coupling) provides an efficient method for the synthesis of N-alkyl and N-arylsubstituted propargyl amines, but this strategy is not amenable for the direct enantioselective synthesis of propargyl amide. We have developed a new strategy and report here a Rh-catalyzed asymmetric hydroalkynylation of enamides. Alkynylations occur regioselectively at the α position of an enamide to produce chiral propargyl amides. High yield and enantioselectivity were observed. Previous alkynylation methods to prepare chiral propargyl amine involve the nucleophilic addition to an electrondeficient imine. In contrast, our current approach proceeds through regioselective hydroalkynylation of an electron-rich alkene. Kinetic studies indicated that migratory insertion of the enamide to the rhodium hydride is turnover limiting. Computational studies revealed the origin of regio- and enantioselectivities. This novel strategy provides an efficient method to access chiral propargyl amides directly from terminal alkynes. [ABSTRACT FROM AUTHOR]

A new DTBP/Mg(NO3)2-mediated bicyclization cascade of o-arylalkynylanilines with secondary arylphosphine oxides has been developed, enabling dual C(sp2)-H functionalization along with the cleavage of the C-N bond. The combination between regioselective P-centered radical-triggered [3 + 2] cyclization and C-centered radical-induced cross-coupling in a one-pot manner delivered 27 examples of tribenzo[b,e,g]phosphindole oxides with generally high regioselectivity. A reasonable mechanism for forming such products involving radical addition-cyclization cascade is proposed. [ABSTRACT FROM AUTHOR]

A new C-center radical-triggered bicyclization cascade of N-tethered 1,7-enynes for forming 28 examples of biologically interesting spirocyclohexadienone-containing cyclopenta[c]quinolin-4-ones with two all-carbon quaternary stereocenters has been established under mild conditions. The in situ generated diazonium salts from 4-methoxyanilines and t-BuONO are served as 4-methoxyphenyl precursors without additional oxidant, enabling 6-exo-dig cyclization/5-exo-trigipso-cyclization to construct three new C-C bonds through metal-free dearomatization. The reaction also features broad substrate scope, annulation efficiency, and high functional group tolerance. [ABSTRACT FROM AUTHOR]

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here, we developed a microfluidic droplet-based thermal shift assay (dTSA) system for high-throughput screening of small-molecule protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 x 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96- or 384-well plate-based systems. We also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its potential in drug discovery, we applied the dTSA system in screening inhibitors of human thrombin with a commercial library containing 100 different small molecule compounds, and two inhibitors were successfully identified and confirmed. [ABSTRACT FROM AUTHOR]

With the use of a simple sulfur-olefin ligand, a highly enantioselective rhodium-catalyzed addition of arylboroxines to N,N-dimethylsulfamoyl-protected aldimines has been achieved, allowing access to a broad range of chiral diarylmethylamines in high yields (up to 98%) with uniformly excellent enantioselectivities (up to 99% ee). This catalyst system is also applicable to the arylation of N-tosyl arylimines. By utilizing this method, some biologically active molecules possessing a chiral 1-aryl-1,2,3,4-tetrahydroisoquinoline core such as Solifenacin and (S)-(+)-Cryptostyline II are facilely constructed. [ABSTRACT FROM AUTHOR]

Here we developed the surface-assisted multifactor fluid segmentation (SAMFS), an automated, fast, and flexible approach for generating a two-dimensional droplet array with tunable droplet volumes, for multivolume digital polymerase chain reaction (PCR). The SAMFS was developed based on the combination of robotic liquid handling and surface-assisted droplet generation techniques, where a continuous aqueous stream that flowed out from a capillary probe was segmented and immobilized on hydrophilic micropillars of a microchip into massive oil-covered droplets with the probe rapidly scanning over the microchip. We studied various factors affecting the droplet generation process, including micropillar top area, distance between adjacent micropillars, aqueous stream flow rate, and microchip moving speed, and demonstrated a high droplet generation throughput up to 50 droplets/s and a largest droplet volume adjusting range from 0.25 to 350 nL. The SAMFS approach was adopted to form an oil-covered array of 994 droplets with four different volumes (1.2, 6, 30, and 150 nL droplets) required for multivolume digital PCR within 8 min. The droplet array system was applied in absolute quantification of plasmid DNA under the multivolume digital PCR mode with a dynamic range spanning 4 orders of magnitude, as well as measurement of HER2 expression levels in different breast cancer cell lines. The results are consistent to those obtained by quantitative real-time PCR method, while the present one has higher precision. [ABSTRACT FROM AUTHOR]

A base-free process to access indole-fused polyheterocycles via a highly efficient and atom-economic palladium-catalyzed intramolecular cross dehydrogenetive coupling (CDC) reaction of 4-aniline substituted coumarins, quinolinones, and pyrones has been developed. A wide range of indolo[3,2-c]coumarins, indolo[3,2-c]quinolinones, and indolo[3,2-c]pyrones can be facilely afforded in good to excellent yields (up to 99%). [ABSTRACT FROM AUTHOR]

The release of nanomaterials into the environment, due to their massive production and application today, has caused ecological and health safety concerns. Semiconductor photocatalysts like TiO2 exhibit cytotoxicity to bacterial cells when exposed to UV irradiation. However, information about their impacts on individual or group bacterial behaviors is limited. In this work, the biofilm formation of Escherichia coli K12 in the presence of TiO2 with and without UV irradiation was investigated and biofilm formation was found not to be affected under the sole application of TiO2 or UV irradiation. However, biofilm development was substantially delayed by TiO2 under UV irradiation, although no obvious cytotoxicity to cell growth was observed. The reactive oxygen species photogenerated by TiO2 were found to quench the autoinducer 2 (AI-2) signals secreted by E. coli K12. As a result, the initiation of quorum sensing for biofilm formation activated by AI-2 was restrained. The expressions of two biofilm-formation-related genes, motA and rcsB, were also suppressed. A dose of an AI-2 precursor, 4,5-dihydroxy-2,3-pentanedione, effectively restored the biofilm development. These results show that the photoexcited TiO2 could suppress biofilm formation through quenching AI-2 signals. This work may facilitate a better understanding about the ecological effects of increasingly released nanomaterials and provide implications for development of antifouling membranes. [ABSTRACT FROM AUTHOR]

Organic molecular cage (CC3-R) with intrinsically porous skeleton is used as a support for immobilizing Rh nanoparticles (NPs) in an ultrasmall size of ~1.1 nm for the first time. The CC3-R with the unique characteristic of high solubility can be utilized to homogenize the heterogeneous catalyst in solution. The obtained homogenized heterogeneous catalyst Rh/CC3-R-homo exhibits significantly enhanced catalytic performance toward various liquid-phase catalytic reactions, as compared with the heterogeneous counterpart Rh/CC3- R-hetero. Moreover, Rh/CC3-R-homo shows excellent durability and recyclability. The advantage of combining homogeneous and heterogeneous catalysts is likely to be beneficial for many applications. [ABSTRACT FROM AUTHOR]

A redox-active diamine ligand, 4,4'-bis(di-p-anisylamino)-2,2'-bipyridine (NNbpy), has been prepared. Electrochemical and spectroscopic studies suggest that little electronic coupling is present between two amine groups in NNbpy. After chelation with Ru(bpy)2 (bpy is 2,2'-bipyridine), the resulting complex displays two N·+/0 processes at +1.02 and +1.16 V versus Ag/AgCl. In the mixed-valent state, rich near-infrared absorptions have been observed, which are believed to consist of multiple metal-to-ligand charge transfer and intervalence charge transfer transitions in the low-energy region. These results suggest that the amine-amine electronic coupling has been enhanced by chelation with Ru(bpy)2. In contrast, no efficient electronic coupling can be realized by chelation with Ir(ppy)2 (ppy is 2'-phenylpyridine) or Re(CO)3Cl. A ruthenium ion-mediated electron transfer mechanism, instead of through-space coupling, has been proposed to explain this phenomenon. For the purpose of comparison, a monoamine-substituted bpy ligand and corresponding Ru(bpy)2 complex have been synthesized and studied. In addition, EPR, DFT, and TDDFT studies have been performed to complement the experimental results [ABSTRACT FROM AUTHOR]

Because porous metal oxides with controllable morphologies have been attracting much attention for their potential applications in the fields of adsorption/separation, sensing, energy storage, and conversion, it is highly desirable to prepare new morphology of metal oxides and investigate their performance. In this work, CuO particles with different shapes such as octahedron, sponge-like octahedron, and sphere have been synthesized through thermal decomposition of crystalline Cu(II)-organic frameworks (HKUST-1). The structure and morphology of as-prepared CuO particles have been fully characterized by the usage of XRD, XPS, SEM, and TEM. The gas-sensing behaviors of these CuO samples have been investigated and our results show that CuO-400 with spherical shape displays unprecedented high response (maximum value, 102) for triethylamine (TEA) at 100 ppm with a low detection limit of 5 ppm, a lower working temperature (230 °C), excellent reproducibility, and long-term stability. The highly sensing behavior of CuO-400 sphere might be due to its special structural factor with many open active sites for oxygen adsorption, which could react with TEA molecules more efficiently. Our results clearly suggest that porous CuO particles should be promising candidates for future practical application to detect TEA vapor at relatively low temperature. [ABSTRACT FROM AUTHOR]

A new luminescent terbium-metal-organic framework [Tb3(L)2(HCOO)(H2O)5]·DMF·4H2O (1) (H4L = 4,4′-(pyridine-3,5-diyl)diisophthalic acid) has been successfully assembled by Tb3+ ions and an undeveloped pyridyl-tetracarboxylate. Compound 1 exhibits a 3D porous (3,8)-connected (4.5²)2(4².512.66.75.8³) topological framework with fascinating 1D open hydrophilic channels decorated by uncoordinated Lewis basic pyridyl nitrogen atoms. In particular, the Tb-MOF (1) can detect Cu2+ ions with high selectivity and sensitivity, and its luminescence is nearly entirely quenched in N,N-dimethylformamide (DMF) solution and biological system. In addition, 1 still has high detection for the trace content of nitromethane with 70 ppm, which suggests that 1 is a promising example of dual functional materials with sensing copper ions and nitromethane. [ABSTRACT FROM AUTHOR]

Stimuli-responsivehydrogels have great potentials in biomedicaland biotechnological applications. Due to the advantages of precisecontrol over molecular weight and being biodegradable, protein-basedhydrogels and their applications have been extensively studied. However,protein hydrogels with dual thermosensitive properties are rarelyreported. Here we present the first report of dual thermosensitivehydrogels assembled from the conserved C-terminal domain of spiderdragline silk. First, we found that recombinant C-terminal domainof major ampullate spidroin 1 (MaSp1) of the spider Nephila clavipesformed hydrogels when cooled toapproximately 2 °C or heated to 65 °C. The conformationalchanges and self-assembly of the recombinant protein were studiedto understand the mechanism of the gelation processes using multiplemethods. It was proposed that the gelation in the low-temperatureregime was dominated by hydrogen bonding and hydrophobic interactionbetween folded protein molecules, whereas the gelation in the high-temperatureregime was due to cross-linking of the exposed hydrophobic patchesresulting from partial unfolding of the protein upon heating. Moreinterestingly, genetic fusion of the C-terminal domain to a shortrepetitive region of N. clavipesMaSp1resulted in a chimeric protein that formed a hydrogel with significantlyimproved mechanical properties at low temperatures between 2 and 10°C. Furthermore, the formation of similar hydrogels was observedfor the recombinant C-terminal domains of dragline silk of differentspider species, thus demonstrating the conserved ability to form dualthermosensitive hydrogels. These findings may be useful in the designand construction of novel protein hydrogels with tunable multiplethermosensitivity for applications in the future. [ABSTRACT FROM AUTHOR]

Cyclometalated diruthenium complexes 1(PF6)2–5(PF6)2 bridged by 1,3,6,8-tetra(pyrid-2-yl)-pyrene have been prepared, with the terminal ligand bis(N-methylbenzimidazolyl)pyridine (1(PF6)2), 4′-di-(p-methoxyphenyl)amino-2,2′:6′,2″-terpyridine (2(PF6)2), 4′-p-methoxyphenyl-2,2′:6′,2″-terpyridine (3(PF6)2), 2,2′:6′,2″-terpyridine (4(PF6)2), and trimethyl-4,4′,4″-tricarboxylate-2,2′:6′,2″-terpyridine (5(PF6)2). The single-crystal X-ray structure of 4(PF6)2 is presented. These complexes show two stepwise anodic redox pairs, and the potentials progressively increase from 1(PF6)2 to 5(PF6)2. Complexes 1(PF6)2–4(PF6)2 have comparable electrochemical potential splitting of 200–210 mV, while complex 5(PF6)2 has a splitting of 170 mV. Upon one-electron oxidation by chemical oxidation or electrolysis, the resulting mixed-valent complexes 13+–53+ display broad and intense absorptions between 1000 and 3000 nm. Complexes 13+ and 23+ show the presence of a higher-energy shoulder band in addition to the main near-infrared absorption band. This shoulder band is less distinguished for 33+–53+. Three-state theory has been used to explain this difference. The one-electron oxidized forms, 13+–53+, exhibit rhombic EPR signals at 77 K with the isotropic g values in the range of 2.18–2.24. Density functional theory (DFT) and time-dependent DFT (TDDFT) computations have been performed on 12+–52+ to characterize their electronic structures and rationalize the absorption spectra in a wide energy range. DFT computations on 13+–53+ show that both ruthenium ions and the bridging ligand have comparable spin densities. TDDFT computations on 13+ and 43+ have been performed to complement the experimental results. [ABSTRACT FROM AUTHOR]

The currently used hemoperfusion adsorbents such as activated carbon and ion-exchange resin show dissatisfactory hemocompatibility, and a large dose of injected heparin leads to the increasing cost and the risk of systematic bleeding. Natural polysaccharide adsorbents commonly have good biocompatibility, but their application is restricted by the poor mechanical strength and low content of functional groups. Herein, we developed an efficient, self-anticoagulant and blood compatible hemoperfusion adsorbent by imitating the structure and functional groups of heparin. Carrageenan and poly(acrylic acid) (PAA) cross-linked networks were built up by the combination of phase inversion of carrageenan and post-cross-linking of AA, and the formed dual-network structure endowed the beads with improved mechanical properties and controlled swelling ratios. The beads exhibited low protein adsorption amounts, low hemolysis ratios, low cytotoxicity, and suppressed complement activation and contact activation levels. Especially, the activated partial thromboplastin time, prothrombin time, and thrombin time of the gel beads were prolonged over 13, 18, and 4 times than those of the control. The self-anticoagulant and biocompatible beads showed good adsorption capacities toward exogenous toxins (560.34 mg/g for heavy metal ions) and endogenous toxins (14.83 mg/g for creatinine, 228.16 mg/g for bilirubin, and 18.15 mg/g for low density lipoprotein (LDL)), thus, highlighting their potential usage for safe and efficient blood purification. [ABSTRACT FROM AUTHOR]

As an iron oxyhydroxide, nanosized ferrihydrite (Fh) is important in Earth science, biology, and industrial applications. However, its basic structure and origin of its magnetism have long been debated. We integrate synchrotron-based techniques to explore the chemical structures of 2-line ferrihydrite and to determine the origin of its magnetism during hydrothermal aging in air. Our results demonstrate that both the magnetism and X-ray magnetic circular dichroism (XMCD. signal of 2-line ferrihydrite are enhanced with aging time, and that XMCD spectral patterns resemble that of maghemite (γ-Fe2O3) rather than magnetite (Fe3O4). Fe L-edge and K-edge X-ray absorption spectroscopy (XAS) further indicate formation of both maghemite and hematite (α-Fe2O3. with increasing concentrations with longer hydrothermal aging time. Thus, magnetic enhancement with longer hydrothermal aging time is attributed to increasing maghemite concentration instead of a magnetically ordered ferrihydrite as previously reported. Moreover, L-edge and K-edge XAS spectra with different probing depths yield different ratios of these Fe oxides, which suggest the formation of a core (ferrihydrite-rich)-shell (with a mixture of both allotropes; α-Fe2O3 and γ-Fe2O3) structure during hydrothermal aging. Our results provide insights into the chemical evolution of 2-line ferrihydrite that reveal unambiguously the origin of its magnetism. [ABSTRACT FROM AUTHOR]

Numerous drug treatments are available for Parkinson's disease (PD), an age-related neurodegenerative disease, but most cause serious side effects. Therefore, novel therapeutic strategies that halt disease progression and allow for long-term administration are urgently needed. Neuroinflammation critically contributes to the pathogenesis of PD. Here, we report the discovery and optimization of phloroglucinol derivatives, a novel class of anti-neuroinflammatory compounds. Structural modifications of the hit compound 3-methyl-1-(2,4,6-trihydroxyphenyl)butan-1-one produced 43 derivatives, including a preclinical candidate (compound 21), that exhibited potent in vitro anti-neuroinflammatory effects, good blood-brain barrier penetration, and desirable safety margins in mice at a median lethal dose (LD50) <5000 mg/kg. Its in vivo efficacy was demonstrated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and MPTP/probenecid (prob)-induced subacute and chronic PD models, respectively, and α-synuclein transgenic mice. Mechanistic studies revealed neuroinflammation inhibition by targeting Src/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt signaling might be promising. We highlighted the potential usefulness of phloroglucinol derivatives in PD treatment. [ABSTRACT FROM AUTHOR]

An asymmetric dual-metal relay catalysis strategy that combines Rh/chiral sulfur-olefin-catalyzed enantioselective 1,2-addition with a Pd-catalyzed intramolecular C--O coupling has been developed. The method allows rapid and efficient synthesis of quaternary carbon-containing gem-diaryl benzofuran-3(2H)-ones in good yields in a highly enantioselective manner (up to 99% ee) through a simple one-pot cascade reaction. [ABSTRACT FROM AUTHOR]

Two new three-dimensional (3D) multinodal Cd(II)-organic frameworks, [Cd3(dccpa)(bipy)0.5(H2O)4]·5H2O (1) and [(CH3)2NH2]2[Cd11(dccpa)4(DMF)4(H2O)8]·4H2O (2) (H6dccpa = 3,4-di(3,5-dicarboxyl phenyl) phthalic acid, bipy = 4,4′-bipyridine), have been prepared and fully characterized. Compound 1 possesses a 3D neutral framework with a new (6,6,7)-connected topology based on a single trinuclear cluster, while 2 features a 3D anionic framework with a new (5,6,6,10)-connected topology containing mixed trinuclear and pentanuclear clusters. Remarkably, 1 and 2 show promising photocatalytic activities toward the degradation of rhodamine B and methyl blue, which suggests that different kinds of cluster units may exert different impacts on the decomposition of organic dyes. [ABSTRACT FROM AUTHOR]

Group IVB transition metal (Zr and Hf) dichalcogenide (TMD) monolayers can have higher carrier mobility and higher tunneling current density than group V1B (Mo and W) TMD monolayers. Here we report the synthesis of hexagonal ZrS2 monolayer and few layers on hexagonal boron nitride (BN) using ZrCl4 and S as precursors. The domain size of ZrS2 hexagons is around 1-3 µm. The number of layers of ZrS2 was controlled by tuning the evaporation temperature of ZrCl4. The stacking angle between ZrS2 and BN characterized by transmission electron microscopy shows a preferred stacking angle of near 0°. Field-effect transistors (FETs) fabricated on ZrS2 flakes showed n-type transport behavior with an estimated mobility of 0.1-1.1 cm² V-1 s-1. [ABSTRACT FROM AUTHOR]

A stable porous carbazole-based luminescent metal-organic framework, NENU-522, was successfully constructed. It is extremely stable in air and acidic/basic aqueous solutions, which provides the strategy for luminescent material encapsulation of Ln3+ ions with tunable luminescence for application in light emission. More importantly, Ln3+@NENU-522 can emit white light by encapsulating different molar ratios of Eu3+ and Ln3+ ions. Additionally, Ln3+@NENU-522 is found to be useful as a fluorescent indicator for the qualitative and quantitative detection of nitroaromatic explosives with different numbers of -NO2 groups, and the concentrations of complete quenching are about 2000, 1000, and 80 ppm for nitrobenzene, 1,3-dinitrobenzene, and 2,4,6-trinitrophenol, respectively. Meanwhile, Ln3+@NENU-522 displays high selectivity and recyclability in the detection of nitroaromatic explosives. [ABSTRACT FROM AUTHOR]

In this work, five novel 2D isostructural Cd(II)-lanthanide(III) heterometallic-organic frameworks [CdCl(L)EuxTby(H2O)(DMA)](NO3)·3DMA (IFMC-36-EuxTby: x = 1, y = 0, IFMC-36-Eu; x = 0.6, y = 0.4, IFMC-36-Eu0.6Tb0.4; x = 0.5, y = 0.5, IFMC-36-Eu0.5Tb0.5; x = 0.4, y = 0.6, IFMC-36-Eu0.4Tb0.6; x = 0, y = 1, IFMC-36-Tb; H3L is 4,4',4"-((2,2',2"-(nitrilotris(methylene))tris(1H-benzo[d]imidazole-2,1-diyl))tris(methylene))tribenzoic acid; IFMC = Institute of Functional Material Chemistry) have been successfully synthesized by taking advantage of different molar ratios of lanthanide(III) (Ln(III)) and metalloligands under solvothermal conditions. Further luminescent measurements indicate that IFMC-36-EuxTby exhibits characteristic sharp emission bands of Eu(III) and Tb(III), and the intensities of red and green can be modulated correspondingly by tuning the ratios of Eu(III) and Tb(III). Particularly, the solvent-dependent luminescent behavior of IFMC-36-Eu shows a potential application in detection of small-molecule pollutant nitrobenzene by significant fluorescence quenching. Furthermore, IFMC-36-Eu displays preeminent anti-interference ability and could be used for sensing in the systems with complicated components. This is the first time that a d-f heterometallic-organic framework can be investigated as a chemical sensor for selective, sensitive, and recyclable detection of nitrobenzene. [ABSTRACT FROM AUTHOR]