Capillary electrophoretic investigation of the enantioselective metabolism of propafenone by human cytochrome P-450 SUPERSOMES: Evidence for atypical kinetics by CYP2D6 and CYP3A4

An enantioselective CE method was used to identify the ability of CYP450 enzymes and their stereoselectivity in catalyzing the transformation of propafenone (PPF) to 5-hydroxy-propafenone (5OH-PPF) and N-despropyl-propafenone (NOR-PPF). Using in vitro incubations with single CYP450 enzymes (SUPERSOMES), 5OH-PPF is shown to be selectively produced by CYP2D6 and N-dealkylation is demonstrated to be mediated by CYP2D6, CYP3A4, CYP1A2, and CYP1A1. For the elucidation of kinetic aspects of the metabolism with CYP2D6 and CYP3A4, incubations with individual PPF enantiomers and racemic PPF were investigated. With the exception of the dealkylation in presence of R-PPF only, which can be described by the Michaelis-Menten model, all CYP2D6-induced reactions were found to follow autoactivation kinetics. For CYP3A4, all NOR-PPF enantiomer formation rates as function of PPF enantiomer concentration were determined to follow substrate inhibition kinetics. The formation of NOR-PPF by the different enzymes is stereoselective and is reduced significantly when racemic PPF is incubated. Clearance values obtained for CYP3A4 dealkylation are stereoselective whereas those of CYP2D6 hydroxylation are not. This paper reports the first investigation of the PPF hydroxylation and dealkylation kinetics by the CYP2D6 enzyme and represents the first report in which enantioselective CE data provide the complete in vitro kinetics of metabolic steps of a drug.     

Collocated discrete least squares meshless (CDLSM) method for the solution of transient and steady‐state hyperbolic problems

A collocated discrete least squares meshless method for the solution of the transient and steady‐state hyperbolic problems is presented in this paper. The method is based on minimizing the sum of the squared residuals of the governing differential equation at some points chosen in the problem domain as collocation points. The collocation points are generally different from nodal points, which are used to discretize the problem domain. A moving least squares method is employed to construct the shape functions at nodal points. The coefficient matrix is symmetric and positive definite even for non‐symmetric hyperbolic differential equations and can be solved efficiently with iterative methods. The proposed method is a truly meshless method and does not require numerical integration. Advantages of the collocation points are shown to be threefold: First, the collocation points are shown to be responsible for stabilizing the method in particular when problems with shocked solution are attempted. Second, the collocation points are also shown to improve the accuracy of the solution even for problems with smooth solutions. Third, the collocation points are shown to contribute to the efficiency of the method when solving steady‐state problems via faster convergence of the resulting algorithm. The ability of the method and in particular the effect of collocation points are tested against a series of one‐dimensional transient and steady‐state benchmark examples from the literature and the results are presented. A sensitivity analysis is also carried out to investigate the effect of the base polynomials on the accuracy and convergence characteristics of the method in solving steady‐state problems. The results show the ability of the proposed method to accurately solve difficult hyperbolic problems considered. The method is also shown to be particularly stable for problems with shocked solution due to the inherent stabilizing mechanism of the method. Copyright © 2008 John Wiley & Sons, Ltd.     

Sub-100 nm structuring of indium-tin-oxide thin films by sub-15 femtosecond pulsed near-infrared laser light

In magnetron sputtered indium-tin-oxide thin films of varying oxygen content, nanostructures were formed using tightly focused high-repetition rate near-infrared sub-15 femtosecond pulsed laser light. At radiant exposure well beyond the ablation threshold, cuts of 280-350 nm in width were generated. Illumination close to the ablation threshold resulted in periodic cuts of typically 20 nm in width at periodicities between 50 nm and 180 nm, as well as single sub-20 nm cuts. Subthreshold exposure, in combination with hydrochloric acid etching, yielded nanowires of 50 nm minimum lateral dimensions.     

Tantalum Electrodes Modified With Well-Aligned Carbon Nanotube–Au Nanoparticles: Application to the Highly Sensitive Electrochemical Determination of Cefazolin

Carbon nanotube/nanoparticle hybrid materials have been proven to exhibit high electrocatalytic activity suggesting broad potential applications in the field of electroanalysis. For the first time, modification of Ta electrode with aligned multi-walled carbon nanotubes/Au nanoparticles introduced for the sensitive determination of the antibiotic drug, cefazolin (CFZ). The electrochemical response characteristics of the modified electrode toward CFZ were investigated by means of cyclic and linear sweep voltammetry. The modified electrode showed an efficient catalytic activity for the reduction of CFZ, leading to a remarkable decrease in reduction overpotential and a significant increase of peak current. Under optimum conditions, the highly sensitive modified electrode showed a wide linear range from 50 pM to 50 μM with a sufficiently low detection limit of 1?±?0.01 pM (S/N?=?3). The results indicated that the prepared electrode presents suitable characteristics in terms of sensitivity (458.2?±?2.6 μAcm^?2/μM), accuracy, repeatability (RSD of 1.8 %), reproducibility (RSD of 2.9 %), stability (14 days), and good catalytic activity in physiological conditions. The method was successfully applied for accurate determination of trace amounts of CFZ in pharmaceutical and clinical preparations without the necessity for samples pretreatment or any time-consuming extraction or evaporation steps prior to the analysis.     

β-Position Electronic Effects on the Singlet–Triplet Gaps of Divalent Five-Membered Rings XC4H3M (M˭C,Si, and Ge)

Abstract

Full geometry optimizations were carried out on the singlet and triplet states of β-substituted divalent five-membered rings XC₄H₃M (X? ?NH₂, ?OH, ?CH₃ ?H, ?CH₃, ?Br, ?Cl, ?F, ?CF₃, and ?NO₂; M?C, Si, and Ge) by the B3LYP method by using 6-311++G** basis set. The thermal energy gaps, ΔE_t–s; enthalpy gaps, ΔH_t–s; and Gibbs free energy gaps, ΔG_t–s, between the singlet (s) and triplet (t) states of the above structures were calculated by using the GAUSSIAN 03 program. The ΔG_t–s of XC₄H₃C was changed in the order: X? ?Cl > ?Br > ?CH₃ > ?H > ?CF₃ > ?F > ?NO₂ > ?OH > ?NH₂. The changes of ΔG_t–s for XC₄H₃Si and XC₄H₃Ge were in the order: X? ?NH₂ > OH > F > Cl > Br > CH₃ > H > CF₃ > NO₂. The geometrical parameters, including bond lengths (R), bond angles (A), dihedral angles (D), natural bonding orbital (NBO) charge at atoms, HOMO and LUMO, and dipole moments, were presented and discussed.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT      

Enhanced photocatalytic activities of TiO<Subscript>2</Subscript>–SiO<Subscript>2</Subscript> nanohybrids immobilized on cement-based materials for dye degradation

Using cement-based material as a matrix for photocatalytic hybrids is an important development for the large-scale application of photocatalytic technologies. In this work, photocatalytic activity of nanosized hybrids of TiO₂/SiO₂ (nano-TiO₂–SiO₂) for degradation of some organic dyes on cementitious materials was highlighted. For this purpose, an optimal inorganic sol–gel precursor was firstly applied to prepare the composites of nano-TiO₂–SiO₂ which was characterized by XRD, SEM and UV–Vis. Then, a thin layer was successfully coated on white Portland cement (WPC) blocks using a dipping process in a nano-TiO₂–SiO₂ solution. The effect of nano-TiO₂–SiO₂-coated WPC blocks on photocatalytic decomposition of three dyes, including Malachite green oxalate (MG), Methylene blue (MB) and Methyl orange (MO) were studied under UV irradiation and monitored by chemical oxygen demand tests. The results showed an increase in photocatalytic effects which depends on the structure and pH of the applied cement.     

First principle study of magnetic and electronic properties of single X (X = Al,Si) atom added to small carbon clusters (C<Subscript> <Emphasis Type="Italic">n</Emphasis> </Subscript>X, <Emphasis Type="Italic">n</Emphasis> = 2–10)

In this paper, the magnetic and electronic properties of single aluminum and silicon atom added to small carbon clusters (C_nX; X = Al, Si; n = 2–10) are studied in the framework of generalized-gradient approximation using density functional theory. The calculations were performed for linear, two dimensional and three dimensional clusters based on full-potential local-orbital (FPLO) method. The total energies, HOMO–LUMO energy gap and total magnetic moments of the most stable structures are presented in this work. The calculations show that C_nSi clusters have more stability compared to C_nAl clusters. In addition, our magnetic calculations were shown that the C_nAl isomers are magnetic objects whereas C_nSi clusters are nonmagnetic objects.     

Chemoselective entry to 5-mercaptotriazoles by condensation of acetylenic esters with triphenylphosphine

A new kind of 1,2,4-triazol derivatives containing ylide moiety were designed and synthesized. The reaction is performed by condensation of dialkyl acetylenedicarboxylate with 5-aryl-2H-1,2,4-triazol-3-thiol in the presence of Ph₃P. In these cases, the reactions take place on the sulfur atom in good to excellent yields via a chemoselective manner.     

Simultaneous X‐ray fluorescence and scanning X‐ray diffraction microscopy at the Australian Synchrotron XFM beamline

Owing to its extreme sensitivity, quantitative mapping of elemental distributions via X‐ray fluorescence microscopy (XFM) has become a key microanalytical technique. The recent realisation of scanning X‐ray diffraction microscopy (SXDM) meanwhile provides an avenue for quantitative super‐resolved ultra‐structural visualization. The similarity of their experimental geometries indicates excellent prospects for simultaneous acquisition. Here, in both step‐ and fly‐scanning modes, robust, simultaneous XFM‐SXDM is demonstrated.     

Image quality assessment using the singular value decomposition theorem

In objective image quality metrics, one of the most important factors is the correlation of their results with the perceived quality measurements. In this paper, a new method is presented based on comparing between the structural properties of the two compared images. Based on the mathematical concept of the singular value decomposition (SVD) theorem, each matrix can be factorized to the products of three matrices, one of them related to the luminance value while the two others show the structural content information of the image. A new method to quantify the quality of images is proposed based on the projected coefficients and the left singular vector matrix of the disturbed image based on the right singular vector matrix of the original image. To evaluate this performance, many tests have been done using a widespread subjective study involving 779 images of the Live Image Quality Assessment Database, Release 2005. The objective results show a high rate of correlation with subjective quality measurements.