Andresenbro6413

Deterium-labeled (hetero)aryl bromide is one of the most widespread applicable motifs to achieve important deuterated architectures for various scientific applications. Traditionally, these deterium-labeled (hetero)aryl bromides are commonly prepared via multistep syntheses. Herein, we disclose a direct H/D exchange protocol for deuteration of (hetero)aryl bromides using Ag2CO3 as catalyst and D2O as deuterium source. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of over 55 (hetero)aryl bromides including bioactive druglike molecules and key intermediates of functional materials. In addition, this method showed distinguishing site-selectivity toward the existing transition-metal-catalyzed HIE process, leading to multideuterated (hetero)aryl bromides in one step.In an earlier investigation, amorphous celecoxib was shown to be sensitive to compression-induced destabilization. This was established by evaluating the physical stability of uncompressed/compressed phases in the supercooled state (Be̅rziņš . Mol. Apalutamide Pharmaceutics, 2019, 16(8), 3678-3686). In this study, we investigated the ramifications of compression-induced destabilization in the glassy state as well as the impact of compression on the dissolution behavior. Slow and fast melt-quenched celecoxib disks were compressed with a range of compression pressures (125-500 MPa) and dwell times (0-60 s). These were then monitored for crystallization using low-frequency Raman spectroscopy when kept under dry (∼20 °C; less then 5% RH) and humid (∼20 °C; 97% RH) storage conditions. Faster crystallization was observed from the samples, which were compressed using more severe compression parameters. Furthermore, crystallization was also affected by the cooling rate used to form the amorphous phases; slow melt-quenched samples exhibited higher sensitivity to compression-induced destabilization. The behavior of the melt-quench disks, subjected to different compression conditions, was continuously monitored during dissolution using low-frequency Raman and UV/vis for the solid-state form and dissolution properties, respectively. Surprisingly the compressed samples exhibited higher apparent dissolution (i.e., higher area under the dissolution curve and initial celecoxib concentration in solution) than the uncompressed samples; however, this is attributed to biaxial fracturing throughout the compressed compacts yielding a greater effective surface area. Differences between the slow and fast melt quenched samples showed some trends similar to those observed for their storage stability.A catalytic enantioselective reduction of α-trifluoromethylated imines by a BINOL-derived boro-phosphate employing catecholborane as hydride source has been developed. This method provides an efficient route to prepare synthetically useful chiral α-trifluoromethylated amines in high yields and with excellent enantioselectivities (up to 98% yield and 96% ee) under mild conditions.Lung metastasis is a fatal and late-stage event for many solid tumors. Multiple lines of evidence have demonstrated that diallyl trisulfide (DATS), an active ingredient of garlic, possesses striking antimetastatic effects. However, the lack of highly efficient organ-compatible carriers restricts its application. In the present study, we showed that extracellular microparticles encapsulated with DATS (DATS-MPs) were capable of interfering with the prometastatic inflammatory microenvironment in local tissues. DATS-MPs were successfully prepared and exhibited typical characteristics of B16BL6-derived extracellular vesicles. The DATS-MPs preferentially fused with cancer cells and endogenous cells (mouse lung epithelial MLE-12 cells) from the metastatic organs in vitro. More interestingly, the systemically administered MPs predominantly accumulated in the lung tissue that serves as their main metastatic organ. The drug-loaded MPs exerted higher antimetastatic effects than DATS alone in both the spontaneous and the experimental metastasis models in mice (*p less then 0.05). Additionally, we found that DATS-MPs inhibited tumor cell migration and interfered with the prometastatic inflammatory microenvironment via decreasing the release of S100A8/A9, serum amyloid A (SAA), and interleukin-6 (IL-6) and inhibiting the expression of fibronectin, MRP8, myeloperoxidase (MPO), and the toll-like receptor 4 (TLR4)-Myd88 in the lung tissues. Collectively, DATS-MPs appeared to enhance the antimetastatic efficiency of DATS in animal models under study.DNA barcoding provides a way to label a myriad of different biological molecules using the extreme programmability in DNA sequence synthesis. Fluorescence imaging is presumably the most easy-to-access method for DNA barcoding, yet large spectral overlaps between fluorescence dyes severely limit the numbers of barcodes that can be detected simultaneously. We here demonstrate the use of single-molecule fluorescence resonance energy transfer (FRET) to encode virtual signals in DNA barcodes using conventional two-color fluorescence microscopy. By optimizing imaging and biochemistry conditions for weak DNA hybridization events, we markedly enhanced accuracy in our determination of the single-molecule FRET efficiency exhibited by each binding event between DNA barcode sequences. This allowed us to unambiguously differentiate six DNA barcodes encoding different FRET values without involving any probe sequence exchanges. Our method can be directly incorporated with previous DNA barcode techniques, and may thus be widely adopted to expand the signal space of DNA barcoding.Solar vapor generation represents a promising approach to alleviate water shortage for producing fresh water from undrinkable water resources. Although Cu-based plasmonics have attracted tremendous interest due to efficient light-to-heat conversion, their application faces great challenges in the oxidation resistance of Cu and low evaporation rate. Herein, a hybrid of three-dimensional carbonized loofah sponges and graphene layers encapsulated Cu nanoparticles is successfully synthesized via a facile pyrolysis method. In addition to effective light harvesting, the localized heating effect of stabilized Cu nanoparticles remarkably elevated the surface temperature of Cu@C/CLS to 72 °C, and a vapor generation rate as high as 1.54 kg m-2 h-1 with solar thermal efficiency reaching 90.2% under 1 Sun illumination was achieved. A study in the purification of sewage and muddy water with Cu@C/CLS demonstrates a promising perspective in a practical application. These results may offer a new inspiration for the design of efficient nonprecious Cu-based photothermal materials.Density functional theory computations have elucidated the mechanism and origins of stereoselectivity in McGlacken's aldol-Tishchenko reaction for the diastereoselective synthesis of 1,3-amino alcohols using Ellman's t-butylsulfinimines as chiral auxiliaries. Variations of stereochemical outcome are dependent on the nature of the ketone starting materials used, and the aspects leading to these differences have been rationalized. The intramolecular hydride transfer step is the rate- and stereochemistry-determining step, and all prior steps are reversible.A novel glucose derivative (CN7DG) possessing an isonitrile as a coordinating group was synthesized, and 99mTc-CN7DG, which was expected to be a powerful tumor imaging agent for SPECT, was prepared in a kit by the reaction of CN7DG with SnCl2·2H2O and 99mTcO4-. 99mTc-CN7DG exhibited good stability and was transported via glucose transporters. Biodistribution results in mice bearing A549 tumor models showed that 99mTc-CN7DG had a higher uptake at the tumor sites and better tumor/blood and tumor/muscle ratios than did [18F]FDG and 99mTc-CN5DG. SPECT/CT imaging studies showed obvious accumulation in tumor sites, suggesting that 99mTc-CN7DG is a promising candidate for tumor imaging. Because 99mTc and 188Re stand for a "theranostic pair", 188Re-CN7DG is expected to be prepared as a promising agent for tumor therapy.We have identified a new reactivity of copper/diamine catalysis for the reductive ring-cleavage of isoxazoles to yield fluoroalkylated enaminones. This protocol has the advantage of using commercially available reagents, ease of setting up, broad tolerance of functionality, and is regiospecific and free of defluorination and reduction of reducible functional groups. The utility was demonstrated by a one-step, regioselective synthesis of fluoroalkylated pyrazole-based drugs such as celecoxib, deracoxib, and mavacoxib.Water solubility of PEDOTPSS conducting polymer is achieved by PSS at the expense of disturbing the crystallinity and electron mobility of PEDOT. Recently, PEDOT crystallinity and electron mobility have been improved by treating the PEDOTPSS aqueous solution with 1-ethyl-3-methylimidazolium- (EMIM-) based ionic liquids (IL) EMIMX. The amount of such improvement varies drastically with the anion X coupled to EMIM cation in the IL. Herein, using umbrella-sampling molecular dynamics simulations on the aqueous solutions of a minimal model of PEDOTPSS mixed with various EMIMX ILs, we show that the solvation of each ion in water plays a major role in the free energies of ion binding and exchange. Anions X efficient for the improvement are weakly stabilized by hydration (i.e., hydrophobic) and prefer binding to hydrophobic PEDOT than to hydrophilic EMIM, favoring the ion exchange. In order to fulfill our design principle, a quantitative criterion based on hydration free energy is proposed to select efficient hydrophobic anions X.A family of axially chiral quinazolinone-based heterobiaryls were constructed with high levels of enantiocontrol (up to 94% ee). Convergently, three different synthetic methods have been realized to prepare these valuable compounds including central-to-axial chirality transfer, dynamic kinetic resolution, and phase-transfer catalysis. Importantly, novel P,N-ligands with a π-π stacking can be derived from heterobiaryls by chirality exchange strategy or synthesized directly from complementary phase-transfer catalysis by using the inexpensive chiral quaternary ammonium salt.The properties of a material depend on how its atoms are arranged, and predicting these arrangements from first principles is a longstanding challenge. Orbital-free density functional theory provides a quantum-mechanical model based solely on the electron density, not individual wave functions. The resulting speedups make it attractive for random structure searching, whereby random configurations of atoms are relaxed to local minima in the energy landscape. We use this strategy to map the low-energy crystal structures of Li, Na, Mg, and Al at zero pressure. For Li and Na, our searching finds numerous close-packed polytypes of almost-equal energy, consistent with previous efforts to understand their low-temperature forms. For Mg and Al, the searching identifies the expected ground state structures unambiguously, in addition to revealing other low-energy structures. This new role for orbital-free density functional theory-particularly as continued advances make it accurate for more of the periodic table-will expedite crystal structure prediction over wide ranges of compositions and pressures.