Novel and sensitive UPLC–MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study

A novel and sensitive LC–MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC–MS/MS was operated under the multiple‐reaction monitoring mode using electrospray ionization. Extraction with tert‐butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C₁₈ (50 × 2.1 mm, 1.7 μm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25–3500 ng/mL for SF. The intra‐ and inter‐day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright © 2016 John Wiley & Sons, Ltd.     

Ab-initio calculations of structural,electronic,and optical properties of Zn_3(VO_4)_2

The structural, electronic, and optical properties of Zn_3(VO_4)_2 are investigated using full potential linearized augmented plane wave(FP-LAPW) method within the framework of density functional theory(DFT). Various approaches are adopted to treat the exchange and correlation potential energy such as generalized gradient approximation(GGA),GGA+U, and the Tran–Blaha modified Becke–Johnson(TB-mBJ) potential. The calculated band gap of 3.424 eV by TB-mBJ is found to be close to the experimental result(3.3 eV). The optical anisotropy is analyzed through optical constants,such as dielectric function and absorption coefficient along parallel and perpendicular crystal orientations. The absorption coefficient reveals high absorption(1.5 × 10~(6) cm~(-1)) of photons in the ultraviolet region.     

Novel palladium nanoparticles supported on β‐cyclodextrin@graphene oxide as magnetically recyclable catalyst for Suzuki–Miyaura cross‐coupling reaction with two different approaches in bio‐based solvents

A novel nanocatalyst was designed and prepared. Initially, the surface of magnetic graphene oxide (M‐GO) was modified using thionyl chloride, tris(hydroxymethyl)aminomethane and acryloyl chloride as linkers which provide reactive C═C bonds for the polymerization of vinylic monomers. Separately, β‐cyclodextrin (β‐CD) was treated with acryloyl chloride to provide a modified β‐CD. Then, in the presence methylenebisacrylamide as a cross‐linker, monomers of modified β‐CD and acrylamide were polymerized on the surface of the pre‐prepared M‐GO. Finally, palladium acetate and sodium borohydride were added to this composite to afford supported palladium nanoparticles. This fabricated nanocomposite was fully characterized using various techniques. The efficiency of this easily separable and reusable heterogeneous catalyst was successfully examined in Suzuki–Miyaura cross‐coupling reactions of aryl halides and boronic acid as well as in modified Suzuki–Miyaura cross‐coupling reactions of N‐acylsuccinimides and boronic acid in green media. The results showed that the nanocatalyst was efficient in coupling reactions for direct formation of the corresponding biphenyl as well as benzophenone derivatives in green media based on bio‐based solvents. In addition, the nanocatalyst was easily separable, using an external magnet, and could be reused several times without significant loss of activity under the optimum reaction conditions.     

Medicinal Potential of Isoflavonoids: Polyphenols That May Cure Diabetes

In recent years, there is emerging evidence that isoflavonoids, either dietary or obtained from traditional medicinal plants, could play an important role as a supplementary drug in the management of type 2 diabetes mellitus (T2DM) due to their reported pronounced biological effects in relation to multiple metabolic factors associated with diabetes. Hence, in this regard, we have comprehensively reviewed the potential biological effects of isoflavonoids, particularly biochanin A, genistein, daidzein, glycitein, and formononetin on metabolic disorders and long-term complications induced by T2DM in order to understand whether they can be future candidates as a safe antidiabetic agent. Based on in-depth in vitro and in vivo studies evaluations, isoflavonoids have been found to activate gene expression through the stimulation of peroxisome proliferator-activated receptors (PPARs) (α, γ), modulate carbohydrate metabolism, regulate hyperglycemia, induce dyslipidemia, lessen insulin resistance, and modify adipocyte differentiation and tissue metabolism. Moreover, these natural compounds have also been found to attenuate oxidative stress through the oxidative signaling process and inflammatory mechanism. Hence, isoflavonoids have been envisioned to be able to prevent and slow down the progression of long-term diabetes complications including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Further thoroughgoing investigations in human clinical studies are strongly recommended to obtain the optimum and specific dose and regimen required for supplementation with isoflavonoids and derivatives in diabetic patients.     

Rapid parameterization of small molecules using the force field toolkit

The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions of common classical force fields, for example, General Amber Force Field and CHARMM General Force Field, have posited guidelines for parameterization of small molecules, many technical challenges remain that have hampered their wide‐scale extension. The Force Field Toolkit (ffTK), described herein, minimizes common barriers to ligand parameterization through algorithm and method development, automation of tedious and error‐prone tasks, and graphical user interface design. Distributed as a VMD plugin, ffTK facilitates the traversal of a clear and organized workflow resulting in a complete set of CHARMM‐compatible parameters. A variety of tools are provided to generate quantum mechanical target data, setup multidimensional optimization routines, and analyze parameter performance. Parameters developed for a small test set of molecules using ffTK were comparable to existing CGenFF parameters in their ability to reproduce experimentally measured values for pure‐solvent properties (<15% error from experiment) and free energy of solvation (±0.5 kcal/mol from experiment). © 2013 Wiley Periodicals, Inc.     

Voltammetric Analysis of Oxymetazoline Hydrochloride at Zeolite – Modified Carbon Paste Electrode in Micellar Medium

Simple, sensitive, accurate and inexpensive differential pulse (DPV) and square wave (SWV) voltammetric methods utilizing zeolite modified carbon paste electrode (ZMCPE) were developed for the determination of Oxymetazoline hydrochloride (OXM) in nasal drops. Various experimental parameters were optimized using cyclic voltammetry (CV). Calibration curves were linear over the concentration ranges 9.8×10⁻⁸–3.6×10⁻⁶ M and 9.8×10⁻⁶–9×10⁻⁵ M for DPV and SWV, respectively. The DPV method showed a limit of detection (LOD) of 1.04×10⁻⁷ M. The method was applied for the determination of OXM in pharmaceutical formulation with an average recovery of 101.18 % (%RSD=0.41, n=9).     

Electrochemical characterization of the redox couple of Fe(III)/Fe(II) mediated by grafted polymer electrode

A new grafted polymer electrode (GPE) (polystyrene as polymer) was grafted with acrylonitrile as a monomer using gamma irradiation to produce a new grafted polymer. The redox process of K₃Fe(CN)₆ during cyclic voltammetry was studied by the new GPE. The ratio of Ipc/Ipa >1 of GPE to GCE Ipc/Ipa = 1.7, indicating that this electrode is a reversible electrode and can be used in conductivity studies by voltammetric analysis. The physical properties of the new electrode GP have good hardness, insolubility, and stability at different high temperatures and at different pH. Also, the sensitivity under conditions of cyclic voltammetry is significantly dependent on pH, electrolyte, and scan rate. At different scan rates, two oxidation peaks and two reduction peaks of Fe(III) were observed in a reversible process: Fe(III) Fe(II), and Fe(II) Fe(0). Interestingly, the redox reaction of Fe(III) solution using GPE remained constant even after 15 cycles. It is therefore evident that the GPE possesses some degree of stability. The potential use of the grafted polymer as a useful electrode material is therefore clearly evident.     

Classical force field parameters for the heme prosthetic group of cytochrome c

Accurate force fields are essential for describing biological systems in a molecular dynamics simulation. To analyze the docking of the small redox protein cytochrome c (cyt c) requires simulation parameters for the heme in both the reduced and oxidized states. This work presents parameters for the partial charges and geometries for the heme in both redox states with ligands appropriate to cyt c. The parameters are based on both protein X-ray structures and ab initio density functional theory (DFT) geometry optimizations at the B3LYP/6-31G* level. The simulations with the new parameter set reproduce the geometries of the X-ray structures and the interaction energies between water and heme prosthetic group obtained from B3LYP/6-31G* calculations. The parameter set developed here will provide new insights into docking processes of heme containing redox proteins.     

Phoebegrandine C, a novel proaporphine-tryptamine dimer, from Phoebe grandis (Nees) Merr

A novel proaporphine-tryptamine dimer alkaloid, named phoebegrandine C 1, was isolated from the leaves of Phoebe grandis (Nees) Merr. Its structural elucidation was carried out using spectroscopic techniques, notably 2D NMR.