Scalable Synthesis of TRPV1 Antagonist Bipyridinyl Benzimidazole Derivative via the Suzuki-Miyaura Reaction and Selective SeO2 Oxidation.

In this study, a kilogram-scale synthesis of a potent TRPV1 antagonist, 1, is described. To synthesize bipyridinyl benzimidazole derivative 1, we have developed a scalable Suzuki-Miyaura reaction capable of providing a key intermediate, 6'-methyl-3-(trifluoromethyl)-2,3'-bipyridine 4, on a kilogram scale. Then, unlike the existing oxidation reaction pathway, two synthetic routes that can be applied to mass production of bipyridinyl carboxylic acid intermediate 5 or aldehyde intermediate 6 were developed by appropriately controlling the oxidation reaction using a selenium dioxide oxidizing agent. Using our developed synthetic procedure, which includes Suzuki-Miyaura coupling, selective selenium dioxide oxidation, and benzimidazole formation, multi-kilogram-scale bi-pyridinyl benzimidazole derivative 1 can be synthesized.

Epitaxial superconducting δ-MoN films grown by a chemical solution method.

The synthesis of pure δ-MoN with desired superconducting properties usually requires extreme conditions, such as high temperature and high pressure, which hinders its fundamental studies and applications. Herein, by using a chemical solution method, epitaxial δ-MoN thin films have been grown on c-cut Al(2)O(3) substrates at a temperature lower than 900 °C and an ambient pressure. The films are phase pure and show a T(c) of 13.0 K with a sharp transition. In addition, the films show a high critical field and excellent current carrying capabilities, which further prove the superior quality of these chemically prepared epitaxial thin films.

Self-separated PZT thick films with bulk-like piezoelectric and electromechanical properties.

Self-separated Pb(Zr(0.52)Ti(0.48))O(3) (PZT) films were processed by a hydrothermal deposition and a rapid thermal separation method, followed by a sol-gel filling and sintering process. The films possess excellent piezoelectric and electromechanical properties close to those of bulk material. The maximum remnant polarization is over 30 µC/cm(2) and the electromechanical coupling factor (k(t)) reaches as high as 0.52. The unique microstructure characteristics of the PZT films, such as their highly dense structure, columnar grains, well-connected grain boundaries, and well-dispersed nanopores, could all contribute to the enhanced piezoelectric and electromechanical properties.

Growth-controlled surface roughness in Al-doped ZnO as transparent conducting oxide.

The surface morphology of Al(2)O(3)-doped ZnO (AZO, 2 wt%) thin films varies from a uniform layer to nanorod structure by simply controlling oxygen pressure during growth. All AZO films were deposited on sapphire(0001) substrates using a pulsed laser deposition (PLD) technique. In the low oxygen pressure regime (vacuum approximately 50 mTorr), AZO films grow as a smooth and uniform layer. In the high oxygen pressure regime (100-250 mTorr) AZO thin films with nanorods have formed. Detailed cross-sectional transmission electron microscopy (TEM) and x-ray diffraction (XRD) studies reveal that, besides the obvious variation in the film morphology, the in-plane d spacing of AZO film increases and the out-of-plane d spacing decreases, as oxygen pressure increases. A bilayer AZO film with a nanorod structure on top of a uniform layer was demonstrated by controlling the oxygen pressure for the two layers. Electrical resistivity and optical transmittance measurements were carried out to correlate with the microstructures obtained under different oxygen pressures. The bilayer AZO films could find applications as a transparent conducting oxide (TCO) with a unique light trapping function in thin film solar cells.

Discovery of an Orally Bioavailable Benzofuran Analogue That Serves as a ß-Amyloid Aggregation Inhibitor for the Potential Treatment of Alzheimer's Disease.

We developed an orally active and blood-brain-barrier-permeable benzofuran analogue (8, MDR-1339) with potent antiaggregation activity. Compound 8 restored cellular viability from Aß-induced cytotoxicity but also improved the learning and memory function of AD model mice by reducing the Aß aggregates in the brains. Given the high bioavailability and brain permeability demonstrated in our pharmacokinetic studies, 8 will provide a novel scaffold for an Aß-aggregation inhibitor that may offer an alternative treatment for AD.

Broadband infrared photoluminescence in silicon nanowires with high density stacking faults.

Making silicon an efficient light-emitting material is an important goal of silicon photonics. Here we report the observation of broadband sub-bandgap photoluminescence in silicon nanowires with a high density of stacking faults. The photoluminescence becomes stronger and exhibits a blue shift under higher laser powers. The super-linear dependence on excitation intensity indicates a strong competition between radiative and defect-related non-radiative channels, and the spectral blue shift is ascribed to the band filling effect in the heterostructures of wurtzite silicon and cubic silicon created by stacking faults.

Silylative carbocyclization of allenyl-carbonyl units with Et3SiH catalyzed by rhodium: cis-stereoselective synthesis of homoallylic cycloalkanols.

[reaction: see text] A new procedure for the synthesis of cis-2-triethylsilylvinyl-cyclopentanols and -cyclohexanols from allenyl-aldehydes and -ketones with Et(3)SiH through rhodium-catalyzed silylative carbocyclization is described. The use of Rh(acac)(CO)(2) (1 mol %) to promote the reaction results in a mild and convenient protocol for the three-component assembly.

Direct observation of Lomer-Cottrell locks during strain hardening in nanocrystalline nickel by in situ TEM.

Strain hardening capability is critical for metallic materials to achieve high ductility during plastic deformation. A majority of nanocrystalline metals, however, have inherently low work hardening capability with few exceptions. Interpretations on work hardening mechanisms in nanocrystalline metals are still controversial due to the lack of in situ experimental evidence. Here we report, by using an in situ transmission electron microscope nanoindentation tool, the direct observation of dynamic work hardening event in nanocrystalline nickel. During strain hardening stage, abundant Lomer-Cottrell (L-C) locks formed both within nanograins and against twin boundaries. Two major mechanisms were identified during interactions between L-C locks and twin boundaries. Quantitative nanoindentation experiments recorded show an increase of yield strength from 1.64 to 2.29 GPa during multiple loading-unloading cycles. This study provides both the evidence to explain the roots of work hardening at small length scales and the insight for future design of ductile nanocrystalline metals.

Ferroelectric properties of vertically aligned nanostructured BaTiO3-CeO2 thin films and their integration on silicon.

Epitaxial (BaTiO3)0.5(CeO2)0.5 films have been deposited in vertically aligned nanocomposite form on SrTiO3/TiN buffered Si substrates to achieve high-quality ferroelectrics on Si. The thin TiN seed layer promotes the epitaxial growth of the SrTiO3 buffer on Si, which in turn is essential for the high-quality growth of the vertically aligned nanocomposite structure. X-ray diffraction and transmission electron microscopy characterization show that the films consist of distinct c-axis oriented BaTiO3 and CeO2 phases. Polarization measurements show that the BaTiO3-CeO2 films on Si are actually ferroelectric at room temperature, and the ferroelectric response is comparable to pure BaTiO3 as well as the BaTiO3-CeO2 films on SrTiO3 single-crystalline substrates. Capacitance-voltage measurements show that, instead of decreasing, the Curie temperature increases to 175 and 150 °C for the samples on SrTiO3 and Si substrates, respectively. This work is an essential step towards integrating novel nanostructured materials with advanced functionalities into Si-based devices.

High quality p-type Ag-doped ZnO thin films achieved under elevated growth temperatures.

By correlating the effects of substrate temperature, oxygen pressure and laser energy on the electrical and microstructural properties of Ag-doped ZnO films grown on a sapphire (0001) substrate, p-type conductivity is achieved under various substrate temperatures in the wide range of 250-750 °C. All of the samples were deposited by pulsed-laser deposition under various designed conditions. Hall measurements indicate that the best conductivity is achieved in Ag-ZnO films under a substrate temperature of 500 °C, a partial oxygen pressure of 250-300 mTorr and laser energy between 330 and 345 mJ. The hole-carrier concentration is 2.29 × 10(18) cm(-3), the resistivity is 0.9 Ω cm and the mobility is 3.03 cm(2) V(-1) s(-1). Transmission-electron microscopy (TEM) studies on the p-type films reveal similar microstructural properties to one another, but different properties to that of the n-type films deposited at the same temperatures with different deposition parameters.

A novel organophosphorus hydrolase-based biosensor using mesoporous carbons and carbon black for the detection of organophosphate nerve agents.

To detect organophosphate chemicals, which are used both as pesticides and as nerve agents, a novel biosensor based on organophosphorus hydrolase was developed. By using mesoporous carbon (MC) and carbon black (CB) as an anodic layer, the sensitivity of the sensor to p-nitrophenol (PNP), which is the product of the organophosphorus hydrolase reaction, was greatly improved. The MC/CB/glass carbon (GC) layer exhibited an enhanced amperometric response relative to a carbon nanotube (CNT)-modified electrode because it promoted electron transfer of enzymatically generated phenolic compounds (p-nitrophenol). The well-ordered nanopores, many edge-plane-like defective sites (EDSs), and high surface area of the MC resulted in increased sensitivity, and allowed for nanomolar-range detection of the analyte paraoxon. Thus, MCs are suitable for use in real-time biosensors. Under the optimized experimental conditions, the biosensor had a detection limit of 0.12 microM (36 ppb) and a sensitivity of 198 nA/microM for paraoxon.

A convenient synthesis of alpha-methylene-gamma-butyrolactones from allenyl carbonyl units mediated by Mo(CO)6 through intramolecular cyclocarbonylation.

A novel procedure for the synthesis of cis-fused bicyclic alpha-methylene-gamma-butyrolactones from allenyl carbonyl functionalities via the molybdenum-mediated cyclocarbonylation is described. The use of Mo(CO)(6) with DMSO to promote reaction results in an efficient and convenient protocol through the three-component assembly in high yields.