Sensitive method for the determination of paricalcitol by liquid chromatography and mass spectrometry and its application to a clinical pharmacokinetic study

A highly sensitive, specific and rapid LC‐ESI‐MS/MS method has been developed and validated for the quantification of paricalcitol (PAR) in human plasma (500 μL) using paricalcitol‐d₆ (PAR‐d₆) as an internal standard (IS) as per regulatory guidelines. A liquid–liquid extraction method was used to extract the analyte and IS from human plasma. Chromatography was achieved on Zorbax SB C₁₈ column using an isocratic mobile phase in a gradient flow. The total chromatographic run time was 6.0 min and the elution of PAR and PAR‐d₆ occurred at ~2.6 min. A linear response function was established for the range of concentrations 10–500 pg/mL in human plasma. The intra‐ and inter‐day accuracy and precision values for PAR met the acceptance criteria. The validated assay was applied to quantitate PAR concentrations in human plasma following oral administration of 4 µg capsules to humans. Copyright © 2014 John Wiley & Sons, Ltd.     

Copper nanoparticles in an ionic liquid: an efficient catalyst for the synthesis of bis-(4-hydroxy-2-oxothiazolyl)methanes

Copper nanoparticles were synthesized and characterized by TEM, XRD and UV-vis techniques. The copper nanoparticles in an ionic liquid were employed as a recyclable catalyst for the synthesis of bis-(4-hydroxy-2-oxothiazolyl)methanes in excellent yields and in short reaction times.     

Nickel‐Catalyzed α‐Carbonylalkylarylation of Vinylarenes: Expedient Access to γ,γ‐Diarylcarbonyl and Aryltetralone Derivatives

We report a Ni‐catalyzed regioselective α‐carbonylalkylarylation of vinylarenes with α‐halocarbonyl compounds and arylzinc reagents. The reaction works with primary, secondary, and tertiary α‐halocarbonyl molecules, and electronically varied arylzinc reagents. The reaction generates γ,γ‐diarylcarbonyl derivatives with α‐secondary, tertiary, and quaternary carbon centers. The products can be readily converted to aryltetralones, including a precursor to Zoloft, an antidepressant drug.     

Nickela‐electrocatalyzed Mild C−H Alkylations at Room Temperature

Direct alkylations of carboxylic acid derivatives are challenging and particularly nickel catalysis commonly requires high reaction temperatures and strong bases, translating into limited substrate scope. Herein, nickel‐catalyzed C?H alkylations of unactivated 8‐aminoquinoline amides have been realized under exceedingly mild conditions, namely at room temperature, with a mild base and a user‐friendly electrochemical setup. This electrocatalyzed C?H alkylation displays high functional group tolerance and is applicable to both the primary and secondary alkylation. Based on detailed mechanistic studies, a nickel(II/III/I) catalytic manifold has been proposed.     

Effect of Acetonitrile on the Colloidal Behavior of Conventional Cationic Surfactants: A Combined Conductivity,Surface Tension,Fluorescence and FTIR Study

A comprehensive study the effect of acetonitrile (ACN) with four cationic surfactants, viz. tetradecyltrimethylammonium bromide (TTAB), cetyltrimethylammonium bromide (CTAB), cetylpyridinium chloride (CPC) and cetylpyridinium bromide (CPB) was made by using the conductivity, surface tension, fluorescence and FTIR techniques. Significant micellar, interfacial and thermodynamic properties were studied by the tensiometeric and conductivity methods. The critical micelle concentration (CMC), aggregation number (Nagg), and Stern–Volmer constants (Ksv) have also been studied by the steady state fluorescence method using pyrene as probe. The fluorescence study also supports the CMC results obtained from conductivity and surface tension. FTIR was used to ascertain that the strength of intermolecular interactions such as hydrogen bonding, ion–ion pair interactions and induced dipole interactions between the surfactants and ACN depend upon the head-group of the surfactants. The interaction of surfactants with ACN is energetically favorable and occurs via direct interactions between the surfactants and ACN. The results further revealed that the strength of interactions between the surfactants and ACN follows the order: TTAB > CTAB > CPC > CPB.     

Dependence of enantioselectivity on the ligand/metal ratio in the asymmetric Michael addition of indole to benzylidene malonates: electronic influence of substrates

Simple bis(oxazoline) ligands, especially azabis(oxazolines), can promote the copper(II)-catalyzed Michael addition of indoles to benzylidene malonates with up to >99 % ee (ee=enantiomeric excess), provided that the ligand/metal ratio is tuned meticulously with particular regard to the electronic properties of the substrate. Despite a common paradigm followed in many asymmetric catalyses, an excess of chiral ligand is not always beneficial. In fact any excess of ligand has to be avoided to reach excellent enantioselectivities when electron-rich benzylidene malonates are used. On the contrary, malonates carrying an electron-withdrawing group require an excess of ligand for an optimum ee value. A correlation of optical yields versus the sigma(I) values of several para substituents shows a sigmoid trajectory. In the presence of an additive, such as triflate, the significance of the ligand/metal ratio vanishes and very good enantioselectivities are achieved at any rate--no matter whether electron-donating or withdrawing substituents are present.     

A facile synthesis of terminal arylacetylenes via Sonogashira coupling reactions catalyzed by MCM-41-supported mercapto palladium（0） complex

A variety of terminal arylacetylenes have been conveniently synthesized in good to high yields via Sonogashira coupling of aryl iodides with （trimethylsilyl）acetylene catalyzed by MCM-41-supported mercapto palladium（0） complex, followed by desilylation under mild conditions. This polymeric palladium catalyst can be reused many times without any decrease in activity.     

Binuclear ruthenium(III) Schiff base complexes bearing N(4)O(4) donors and their catalytic oxidation of alcohols

An interesting series of binuclear ruthenium(III) Schiff base complexes bearing bis-salophen/bis-naphophen units of the general composition [(EPh(3))(X)Ru-L-Ru(X)(EPh(3))] (where E=P or As; X=Cl or Br; L=binucleating dianionic tetradentate ligands) have been synthesized and characterized by analytical (elemental analysis, magnetic susceptibility measurements), spectral (FT-IR, UV-vis and EPR) and electrochemical methods. These ruthenium(III) complexes have two N(2)O(2) metal binding sites, which are linked to each other with a biphenyl bridge and acts as potential catalyst for oxidation of wide range of primary and secondary alcohols to corresponding aldehydes or ketones with moderate to high conversion in the presence of N-methylmorpholine-N-oxide (NMO). The formation of high-valent Ru(V)=O species as a catalytic active intermediate is proposed for the catalytic processes.     

Unambiguous structural elucidation of base-modified purine nucleosides using NMR

A general and unambiguous approach has been developed for structural elucidation of modified purine nucleosides using NMR spectroscopy. Systematic assignment of proton and carbon signals of modified nucleosides was firmly established by COSY and the anomerism of the glycosidic linkage of synthetic nucleosides clearly elucidated by NOESY experiments. Characteristic properties of 15N-isotopic labelling at specific positions of nucleosides were also employed for structural studies. The reported approach is applicable to other modified nucleosides and nucleotides, as well as nucleobases.