High-Throughput GC-FID Method for the Determination of Residual Solvents in Early-Phase Drug Discovery Samples

Chromatographia - In drug discovery environment, determination of residual solvents is indispensable and requires rapid analysis covering a maximum number of commonly used solvents especially with...     

Robust tracking control of nonlinear unmatched uncertain systems via event-based adaptive dynamic programming

Nonlinear Dynamics - In this paper, a novel robust tracking control strategy for nonlinear unmatched uncertain systems is formulated using the event-based adaptive dynamic programming (ADP)...     

Improved third‐order weighted essentially nonoscillatory scheme

A new third‐order WENO scheme is proposed to achieve the desired order of convergence at the critical points for scalar hyperbolic equations. A new reference smoothness indicator is introduced, which satisfies the sufficient condition on the weights for the third‐order convergence. Following the truncation error analysis, we have shown that the proposed scheme achieves the desired order accurate for smooth solutions with arbitrary number of vanishing derivatives if the parameter ε satisfies certain conditions. We have made a comparative study of the proposed scheme with the existing schemes such as WENO‐JS, WENO‐Z, and WENO‐N3 through different numerical examples. The result shows that the proposed scheme (WENO‐MN3) achieves better performance than these schemes.     

Regio- and diastereoselective synthesis of anticancer spirooxindoles derived from tryptophan and histidine via three-component 1,3-dipolar cycloadditions in an ionic liquid

A small library of novel hybrid spiroheterocycles containing spirooxindole, pyrrolidine and indole/imidazole moieties were synthesized with complete regio- and diastereoselectively in good to excellent yields from a three-component process starting from a series of variously substituted (E)-(2-nitrovinyl)benzenes, indoline-2,3-dione derivatives and l-tryptophan or l-histidine in an ionic liquid. The key step of this transformation is a 1,3-dipolar cycloaddition reaction involving a rare class of in situ-generated azomethine ylides derived from aromatic amino acids. The compounds thus synthesized were evaluated for their anticancer activity and were shown to inhibit the proliferation of FaDu cells, a human epithelial cell line isolated from a squamous cell carcinoma of the hypopharynx, via apoptotic cell death.     

A fluorescent fluoride ion probe based on a self-organized ensemble of 5-hydroxyflavone-Al(III) complex

In the presence of Al(III) ions, 5-hydroxyflavone (5HF) through a complexation reaction in MeOH, shows dual fluorescence, characterized by a newly developed peak at 554nm upon excitation at 363nm. In this communication, the subsequent ligand exchange reaction of the complex with fluoride ion causing a fluorescence enhancement followed by a decrease in fluorescence intensity involving an intermediate mechanistic pathway, delivering a quantitative estimation route for fluoride ion in the concentration range from 5x10(-5) to 7x10(-4)M, has been reported. The ligand exchange reaction, without interference from other common anions, has been investigated by UV-vis and fluorescence spectroscopies combined with the AM1 semi-empirical self-consistent field quantum chemical calculations within UHF formalism in their ground state.     

Rapid and simple liquid chromatography tandem mass spectrometry method for the quantification of zidovudine in rat plasma

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of zidovudine in rat plasma. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 268/127 for zidovudine and m/z 230/112 for the internal standard. The method exhibited a linear dynamic range of 5-500 ng/mL for zidovudine in rat plasma. The lower limit of quantification was 5 ng/mL with a relative standard deviation of less than 8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 1.5 min for each sample made it possible to analyze more than 400 plasma samples per day. The validated method was applied for pharmacokinetic studies of the novel drug delivery systems of zidovudine in rats.     

Stereoconversion of amino acids and peptides in uryl-pendant binol schiff bases

(S)-2-Hydroxy-2'-(3-phenyluryl-benzyl)-1,1'-binaphthyl-3-carboxaldehyde (1) forms Schiff bases with a wide range of nonderivatized amino acids, including unnatural ones. Multiple hydrogen bonds, including resonance-assisted ones, fix the whole orientation of the imine and provoke structural rigidity around the imine C==N bond. Due to the structural difference and the increase in acidity of the alpha proton of the amino acid, the imine formed with an L-amino acid (1-l-aa) is converted into the imine of the D-amino acid (1-D-aa), with a D/L ratio of more than 10 for most amino acids at equilibrium. N-terminal amino acids in dipeptides are also predominantly epimerized to the D form upon imine formation with 1. Density functional theory calculations show that 1-D-Ala is more stable than 1-L-Ala by 1.64 kcal mol(-1), a value that is in qualitative agreement with the experimental result. Deuterium exchange of the alpha proton of alanine in the imine form was studied by (1)H NMR spectroscopy and the results support a stepwise mechanism in the L-into-D conversion rather than a concerted one; that is, deprotonation and protonation take place in a sequential manner. The deprotonation rate of L-Ala is approximately 16 times faster than that of D-Ala. The protonation step, however, appears to favor L-amino acid production, which prevents a much higher predominance of the D form in the imine. Receptor 1 and the predominantly D-form amino acid can be recovered from the imine by simple extraction under acidic conditions. Hence, 1 is a useful auxiliary to produce D-amino acids of industrial interest by the conversion of naturally occurring L-amino acids or relatively easily obtainable racemic amino acids.     

Zinc oxide nanoparticles-chitosan composite film for cholesterol biosensor

Zinc oxide nanoparticles (NanoZnO) uniformly dispersed in chitosan (CHIT) have been used to fabricate a hybrid nanocomposite film onto indium-tin-oxide (ITO) glass plate. Cholesterol oxidase (ChOx) has been immobilized onto this NanoZnO-CHIT composite film using physiosorption technique. Both NanoZnO-CHIT/ITO electrode and ChOx/NanoZnO-CHIT/ITO bioelectrode have been characterized using Fourier transform-infrared (FTIR), X-ray diffraction (XRD), cyclic voltammetry (CV), scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) techniques, respectively. The ChOx/NanoZnO-CHIT/ITO bioelectrode exhibits linearity from 5 to 300 mg dl⁻¹ of cholesterol with detection limit as 5 mg dl⁻¹, sensitivity as 1.41 × 10⁻⁴ A mg dl⁻¹ and the value of Michaelis-Menten constant (K_m) as 8.63 mg dl⁻¹. This cholesterol biosensor can be used to estimate cholesterol in serum samples.     

Synthesis,Characterization and Photocatalytic Activity of Ag+‐ and Sn2+‐Doped KTi0.5Te1.5O6

In this study, the photocatalytic dye degradation efficiency of KTi_0.5Te_1.5O₆ synthesized through solid‐state method was enhanced by cation (Ag⁺/Sn⁺²) doping at potassium site via ion exchange method. As prepared materials were characterized by XRD, SEM‐EDS, IR, TGA and UV–Vis Diffuse reflectance spectroscopic (DRS) techniques. All the compounds were crystallized in cubic lattice with space group. The bandgap energies of parent, Ag⁺‐ and Sn⁺²‐doped KTi_0.5Te_1.5O₆ materials obtained from DRS profiles were found to be 2.96, 2.55 and 2.40 eV, respectively. Photocatalytic efficiency of parent, Ag⁺‐ and Sn⁺²‐doped materials was evaluated against the degradation of methylene blue (MB) and methyl violet (MV) dyes under visible light irradiation. The Sn⁺²‐doped KTi_0.5Te_1.5O₆ showed higher activity toward the degradation of both MB and MV dyes and its higher activity is ascribed to the lower bandgap energy compared to the parent and Ag⁺‐doped KTi_0.5Te_1.5O₆. The mechanistic degradation pathway of methylene blue (MB) was studied in the presence of Sn²⁺‐doped KTi_0.5Te_1.5O₆. Quenching experiments were performed to know the participation of holes, super oxide and hydroxyl radicals in the dye degradation process. The stability and reusability of the catalysts were studied.