Efficient Synthesis of Spirooxindole Pyrrolones by a Rhodium(III)‐Catalyzed C−H Activation/Carbene Insertion/Lossen Rearrangement Sequence

A rhodium(III)‐catalyzed domino annulation of simple olefins with diazo oxindoles to give spirooxindole pyrrolone products is described. This reaction can be formally viewed as the result of an anomalous tandem C?H activation, carbene insertion, Lossen rearrangement, and a nucleophilic addition process. The potential utility of this reaction was further demonstrated by the late‐stage diversification of drug molecules.     

An LC–MS/MS method for quantification of HR011303, a novel highly selective urate transporter 1 inhibitor in beagle dogs and the application to a pharmacokinetic study

HR011303 is a novel and highly selective urate transporter 1 (URAT1) inhibitor. In this study, a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for quantification of HR011303 in beagle dog plasma. Plasma samples were pretreated with protein‐precipitation extraction by acetonitrile and added with a trifluoromethyl substituted analog of HR011303 as internal standard. The chromatographic separation was performed on a Shiseido C₁₈ column (100 × 4.6 mm, i.d., 5 μm) by mobile phases consisting of 5 mm ammonium–formic acid (100:0.1) and acetonitrile–formic acid (100:0.1) solutions in gradient elution. The MS detection was conducted in electrospray positive ionization with multiple reactions monitoring at m/z 338 → 240 for HR011303 and m/z 328 → 230 for the internal standard using 25 eV argon gas collision induced dissociation. The established LC–MS/MS method showed good selectivity, sensitivity, precision and accuracy. The plasma pharmacokinetics of HR011303 in beagle dogs following both oral and intravenous administration were then successfully evaluated using this LC–MS/MS method.     

Dose‐dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra‐fast liquid chromatography–electrospray ionization–tandem mass spectrometry

Notoginsenoside R₁ (NGR₁), a diagnostic protopanaxatriol‐type (ppt‐type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti‐inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR₁ in rats after oral and intravenous administration and to explore the metabolic characterization of NGR₁. A simple and sensitive ultra‐fast liquid chromatographic–tandem mass spectrometric method was developed and validated for the quantitative determination of NGR₁ and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR₁ exhibited dose‐independent exposure behaviors with t_1/2 over 8.0 h and oral bioavailability of 0.25–0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)‐notoginsenoside R₂/20(S)‐notoginsenoside R₂ and 20(R)‐ginsenoside Rh₁/20(S)‐ginsenoside Rh₁, with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)‐notoginsenoside R₂, ginsenoside Rg₁, ginsenoside F₁ and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.     

Insight into the combustion mechanism of nitroglycerin/nano-aluminum composite materials

Structural Chemistry - The ReaxFF-lg is used to simulate the thermal decomposition of the pure nitroglycerin (NG) and nitroglycerin/nano-Al (NG/Al) systems. The simulation results show that the...     

Growth and spectral properties of Yb:Ca0.28Ba0.72Nb2O6 disordered crystal

The growth, XRD patterns, spectral properties, and fluorescence decays of Yb:Ca_0.28Ba_0.72Nb₂O₆ (Yb:CBN) with doping concentration of 1 at.% and 5 at.% were studied. The peak absorption cross-section and the emission cross-section were calculated. Larger Stark splitting of Yb:CBN offers the prospect of the quasi-four level laser operation.     

Comparative pharmacokinetic study of four major bioactive components after oral administration of Zhi‐Zi‐Hou‐Po decoction in normal and corticosterone‐induced depressive rats

A highly selective and efficient LC–MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi‐Zi‐Hou‐Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra^® MS C₁₈ column using a gradient elution with a mobile phase composed of acetonitrile–0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra‐ and inter‐day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from ?8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and C_max of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi‐Zi‐Hou‐Po to treat depression.     

Persistent luminescence properties of SrMg2(PO4)2:Eu2+,Tb3+

We investigate the persistent luminescence in europium-doped SrMg₂(PO₄)₂ upon codoping with auxiliary terbium. Luminescence properties of the phosphors, including photoluminescence, luminescence decay and thermoluminescence, are systematically studied. SrMg₂(PO₄)₂:Eu²⁺ shows only a weak persistent luminescence, and codoping with Tb³⁺ is necessary to obtain considerable persistent luminescence. An energy level scheme is constructed to convey reasonable trapping and detrapping processes in the material.     

Mechanical and electrical response variation of the polyurethane–tin oxide–carbon nanotube composite microfiber depending on the chemical solution

Toward the goal of smart sensor systems for wearable electronics, polymer microfiber‐based free‐standing sensors benefit from excellent flexibility, decent ductility, and easy wearability in comparison with thin‐film‐based sensing devices. Herein, we report a hydrophobic and conducting single‐strand microfiber‐based liquid‐phase chemical sensor consisting of polyurethane (PU), tin oxide (SnO₂), and carbon nanotube (CNT) composites with applying a (1H,1H,2H,2H‐heptadecafluorodec‐1‐yl) phosphonic acid (HDF‐PA)‐based self‐assembled monolayer. The free‐standing HDF‐PA‐treated PU–SnO₂–CNT composite microfiber showing selective filtering properties with the repellency of water and the penetration of an organic solvent is electrically and mechanically characterized. Finally, the single‐strand HDF‐PA‐treated PU–SnO₂–CNT composite microfiber‐based chemical sensor, which shows excellent mechanical properties and aqueous stability, is demonstrated to detect the presence of a chemical in pure water or counterfeit gasoline in pure gasoline by observing mechanical changes, especially variations in the length and diameter of the fiber, and monitoring the electrical resistance change. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 495–502