Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Finite element computations of viscoelastic two-phase flows using local projection stabilization

A three-field local projection stabilized (LPS) finite element method is developed for computations of a three-dimensional axisymmetric buoyancy driven liquid drop rising in a liquid column where one of the liquid is viscoelastic. The two-phase flow is described by the time-dependent incompressible Navier-Stokes equations, whereas the viscoelasticity is modeled by the Giesekus constitutive equation in a time-dependent domain. The arbitrary Lagrangian-Eulerian (ALE) formulation with finite elements is used to solve the governing equations in the time-dependent domain. Interface-resolved moving meshes in ALE allows to incorporate the interfacial tension force and jumps in the material parameters accurately. A one-level LPS based on an enriched approximation space and a discontinuous projection space is used to stabilize the numerical scheme. A comprehensive numerical investigation is performed for a Newtonian drop rising in a viscoelastic fluid column and a viscoelastic drop rising in a Newtonian fluid column. The influence of the viscosity ratio, Newtonian solvent ratio, Giesekus mobility factor, and the Eötvös number on the drop dynamics are analyzed. The numerical study shows that beyond a critical Capillary number, a Newtonian drop rising in a viscoelastic fluid column experiences an extended trailing edge with a cusp-like shape and also exhibits a negative wake phenomena. However, a viscoelastic drop rising in a Newtonian fluid column develops an indentation around the rear stagnation point with a dimpled shape.     

Effects of pressure rise rate on laminar flame speed under normal and engine-relevant conditions

Laminar flame speed (LFS) is one of the most important physicochemical properties of a combustible mixture. At normal and elevated temperatures and pressures, LFS can be measured using propagating spherical flames in a closed chamber. LFS is also used in certain turbulent premixed flame modelling for combustion in spark ignition engines. Inside the closed chamber or engine, transient pressure rise occurs during the premixed flame propagation. The effects of pressure rise rate (PRR) on LFS are examined numerically in this study. One-dimensional simulations are conducted for spherical flame propagation in a closed chamber. Detailed chemistry and transport are considered. Different values of PRR at the same temperature and pressure are achieved through changing the spherical chamber size. It is found that the effect of PRR on LFS is negligible under the normal and engine-relevant conditions considered in this study. This observation is then explained through the comparison between the unsteady and convection terms in the energy equation for a premixed flame.     

Expanding the Topological Landscape by a G-Column Flip of a Parallel G-Quadruplex

Canonical G-quadruplexes can adopt a variety of different topologies depending on the arrangement of propeller, lateral, or diagonal loops connecting the four G-columns. A novel intramolecular G-quadruplex structure is derived through inversion of the last G-tract of a three-layered parallel fold, associated with the transition of a single propeller into a lateral loop. The resulting (3+1) hybrid fold features three syn⋅anti⋅anti⋅anti G-tetrads with a 3’-terminal all-syn G-column. Although the ability of forming a duplex stem-loop between G-tracts seems beneficial for a propeller-to-lateral loop rearrangement, unmodified G-rich sequences resist folding into the new (3+1) topology. However, refolding can be driven by the incorporation of syn-favoring guanosine analogues into positions of the fourth G-stretch. The presented hybrid-type G-quadruplex structure as determined by NMR spectroscopy may provide for an additional scaffold in quadruplex-based technologies.     

Cp2ZrCl2‐catalyzed synthesis of 2‐substituted quinozolin‐4(3H)‐ones

Zirconocene dichloride (Cp₂ZrCl₂) in the presence of DMF was found to be a highly efficient catalyst for the synthesis of structurally diverse 2‐substituted quinozolin‐4(3H)‐ones by reaction of anthranilimide with a wide range of aryl aldehydes. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,Characterization, and Antimicrobial Studies of Novel Benzodipyran Analog of Chloramphenicol

A synthesis, characterization, and antimicrobial study of a novel benzodipyran analog of chloramphenicol was carried out. Structure–antimicrobial activity relationship study indicates that benzodipyran analog of chloramphenicol was most active against Gram‐positive bacteria, Staphylococcus aureus, and the fungal strains Rhizoctonia bataticola and Penicillium even at minimum inhibitory concentration 10 µg/mL and showed moderate activity in other bacterial and fungal organisms. All the compounds synthesized during the present investigation were characterized by IR, ¹H NMR, ¹³C NMR, ESI‐MS, and elemental analysis.     

Probing the effect of nitrogen gas on electrical conduction phenomena of ZnO and Cu-doped ZnO thin films prepared by spray pyrolysis

Zinc oxide (ZnO) and Cu-doped ZnO (CZO) thin films were prepared on borosilicate glass substrates by spray pyrolysis technique. The X-ray diffraction study revealed that Cu doping caused a reduction in crystallite size. AFM study showed an increase in roughness with doping. This is attributed to the aggregation of particles to form clusters. From transmission electron microscopy analysis, the particle size is measured to be in the range 30–65 nm (average particle size 48 nm) for undoped ZnO, whereas it is in the range 24–56 nm (average particle size 40 nm) for CZO film. The electrical resistivity of the thin films was investigated in the presence of air as well as N₂ mixed air at different temperatures in the range 30–270 °C. The change in resistivity properties was explained on the basis of conduction phenomena within the grain along with the grain boundaries as well as Cu- and N₂-induced defect states. The thermal activation energy of ZnO was found to be in the range 0.04–0.7 eV and dependent on Cu doping and N₂ level in air.     

Facile access to 3-cyano-4-azaindoles via a modified Madelung indole synthesis

An unprecedented methodology for the facile synthesis of 2-substituted 3-cyano-4-azaindoles using modified Madelung synthesis is described. The methodology relies on acid and amine coupling under very mild conditions.     

Diamagnetic and zeeman shifts of the ground state of arsenic donors in germanium

The technique of four-wave mixing spectroscopy has been utilized to study the magnetic field dependence of the valley-orbit splitting, 4△(B), of As donors in Ge at 1.8°K for ⊥ [111]. The upper ground level, ls(T₂), splits into two levels, one of “high” and the other of “low” diamagnetism. For donor concentration N_D ? 5 × 10¹⁵ cm^-3 we have measured the diamagnetism and g-factor for the high diamagnetism level (g ? 1.07) as a function of (< 7 T). Transitions originating from both spin-up and spin-down levels are observed, indicating that the spins are heated during the 100 n-sec laser pulse. Excellent agreement between measured and theoretical values of 4▽(B) is found (employing no adjustable parameters) if magnetic field compression of the wavefunction is taken into account.     

Steady state and transient fluorescence studies of CaF2: Dy single crystals

The steady state and transient fluorescence spectra of CaF₂: Dy³⁺ have been studied using Ar⁺ and N₂ lasers in the temperature range 77–673 K and in the wavelength region 4500–9000 Å. The spectra show the presence of two types of centers (type A and type B) with decay times of 1.3 and 3.5 ms. The observed spectrum is mostly due to type A centers. Three new groups of fluorescence ⁴F_9/2−⁶H_11/2, ⁴F_9/2−(⁶H_9/2, ⁶F_11/2) and ⁴F_9/2−(⁶H_7/2, ⁶F_9/2) have been observed for type A centers, and a tentative assignment of the positions of the Stark levels of ⁶H_11/2, (⁶H_9/2, ⁶F_11/2) and (⁶H_7/2, ⁶F_9/2) has been made. The change in the intensity of the transitions with temperature and excitation wavelength are discussed.