Liquid chromatography/electrospray ionization tandem mass spectrometry validated method for the simultaneous quantification of sibutramine and its primary and secondary amine metabolites in human plasma and its application to a bioequivalence study

A high-throughput and sensitive bioanalytical method using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) has been developed for the estimation of sibutramine and its two metabolites (M1 and M2). The extraction of sibutramine, its metabolites and imipramine (internal standard (IS)) from the plasma involved treatment with phosphoric acid followed by solid-phase extraction (SPE) using a hydrophilic-lipophilic balanced HLB cartridge. The SPE eluate without drying and reconstitution was analyzed by LC/MS/MS, equipped with a with turbo ion spray (TIS) source, operating in the positive and multiple reaction monitoring (MRM) acquisition mode. Sample preparation by this method yielded extremely clean extracts with quantitative and consistent mean recoveries; 95.12% for sibutramine, 92.74% for M1, 95.97% for M2 and 96.60% for the IS. The total chromatographic run time was 3.0 min with retention times of 2.51, 2.13, 2.09 min for sibutramine, M1, M2 and imipramine, respectively. The developed method was validated in human plasma matrix, with a sensitivity of 0.1 ng/mL (coefficient of variance (CV), 2.07%) for sibutramine, 0.1 ng/mL (CV, 3.59%) for M1 and 0.2 ng/mL (CV, 4.93%) for M2. Validation of the method for its accuracy, precision, recovery, matrix effect and stability was carried out especially with regard to real subject sample analysis. The response was linear over the dynamic range 0.1 to 8.0 ng/mL for sibutramine and M1, and 0.2 to 16.0 ng/mL for M2 with correlation coefficients of r > or = 0.9959 (sibutramine), 0.9935 (M1) and 0.9943 (M2). The method was successfully applied for bioequivalence studies in 40 human subjects with 15 mg capsule formulations.     

Stereoselective synthesis of highly O-functionalized enantiopure 2,3,4-trisubstituted tetrahydrofurans by tandem debenzylative cyclization of glycal derived 2,3-epoxy alcohols

A new and highly efficient methodology for the construction of synthetically important highly O-functionalized enantiopure 2,3,4-trisubstituted tetrahydrofurans with three contiguous stereocenters is reported.     

Nitrate-Bridged "Pseudo-Double-Propeller"-Type Lanthanide(III)-Copper(II) Heterometallic Clusters: Syntheses, Structures, and Magnetic Properties

Two discrete nitrate-bridged novel "pseudo-double-propeller"-shaped hexanuclear Cu/Ln clusters of the formula [Cu(4)Ln(2)L(4)L'(4)(NO(3))(2)(OH(2))(2)]·3NO(3)·4H(2)O [Ln = Dy, Gd; LH = o-vanilin; L'H = 2-(hydroxyethyl)pyridine] were synthesized and characterized. Single-crystal X-ray diffraction studies revealed the trimeric half-propeller-type Cu(2)/Ln core connected to other opposite-handed similar trimers by a bridging nitrate ligand. The Dy analogue, [Cu(4)Dy(2)L(4)L'(4)(NO(3))(2)(OH(2))(2)]·3NO(3)·4H(2)O, shows frequency-dependent out-of-phase alternating-current magnetic susceptibility, which indicates that this novel discrete [Cu(4)Dy(2)] heterometallic cluster may exhibit single-molecule-magnet behavior.     

Evolving networks with bimodal degree distribution

Networks with bimodal degree distribution are most robust to targeted and random attacks. We present a model for constructing a network with bimodal degree distribution. The procedure adopted is to add nodes to the network with a probability p and delete the links between nodes with probability (1 − p). We introduce an additional constraint in the process through an immunity score, which controls the dynamics of the growth process based on the feedback value of the last few time steps. This results in bimodal nature for the degree distribution. We study the standard quantities which characterize the networks, like average path length and clustering coefficient in the context of our growth process and show that the resultant network is in the small world family. It is interesting to note that bimodality in degree distribution is an emergent phenomenon.     

Intrinsic bioremediation of gas condensate hydrocarbons

Condensate liquids have been found to contaminate soil and ground water at two gas production sites in the Denver Basin operated by Amoco Production Co. These sites have been closely monitored since July 1993 to determine whether intrinsic aerobic or anaerobic bioremediation of hydrocarbons occurs at a sufficient rate and to an adequate end point to support a no-intervention decision. Ground water monitoring, soil gas analysis, and analysis of soil cores suggest that bioremediation is occurring at these sites by multiple pathways, including aerobic oxidation, sulfate reduction, and methanogenesis. Results of over two years of monitoring of ground water and soil chemistry at these sites are presented to support this conclusion.

     

One-pot synthesis of multicomponent pyrazole-4-carbonitrile derivatives under solvent-free condition by using engineered polyvinyl alcohol catalyst

Heterocyclic chemistry has fascinated the researchers owing to its wide range of applications in various chemical fields. With this perspective, herein we present an environmentally benign procedure for the synthesis of pyrazole and its derivatives through multicomponent reaction by using SPVA as a heterogeneous acid catalyst. The synthesis protocol of SPVA catalyst includes functionalization of polyvinyl alcohol by sulfonic acid groups. The synthesized SPVA catalyst was then subjected to several characterization techniques to confirm its formation and study its physicochemical properties. The SPVA catalyst was then tested for its activity toward a multicomponent reaction of aromatic aldehyde, malononitrile and phenyl hydrazine. The SPVA catalyst with sufficient acidic sites displayed appreciable catalytic performance yielding 89% of the desired pyrazole product under ambient reaction conditions. The SPVA catalyst showed recyclability up to the sixth cycle without considerable loss in its activity. Furthermore, we made an effort to demonstrate the plausible mechanistic pathway for the SPVA-catalyzed pyrazole synthesis reaction. Interestingly, the present synthetic approach could effectively produce pyrazole products with high yields in the absence of base and solvent and in short reaction time making it a green and sustainable process.

Graphic abstract

     

Novel intramolecular rearrangement leading to the synthesis of biheterocyclic indole-benzoimidazole derivatives on solid phase

[reaction: see text] A novel intramolecular SNAr rearrangement observed during the S-alkylation of benzoimidazole-2-thione with alpha-haloacetophenone is reported. The rearrangement led to the formation of a new benzoimidazole-based intermediate, which is further utilized for the generation of a new biheterocyclic indole-benzimidazole derivatives with a two-point diversity.     

Methane production in a 100-L upflow bioreactor by anaerobic digestion of farm waste

Manure waste from dairy farms has been used for methane production for decades, however, problems such as digester failure are routine. The problem has been investigated in small scale (1–2 L) digesters in the laboratory; however, very little scale-up to intermediate scales are available. We report production of methane in a 100-L digester and the results of an investigation into the effect of partial mixing induced by gas upflow/recirculation in the digester. The digester was operated for a period of about 70 d (with 16-d hydraulic retention time) with and without the mixing induced by gas recirculation through an internal draft tube. The results show a clear effect of mixing on digester operation. Without any mixing, the digester performance deteriorated within 30–50 d, whereas with mixing continuous production of methane was observed. This study demonstrates the importance of mixing and its critical role in design of large scale anaerobic digesters.     

Mechanophotonics: Flexible Single-Crystal Organic Waveguides and Circuits

We present the one-dimensional optical-waveguiding crystal dithieno[3,2-a:2′,3′-c]phenazine with a high aspect ratio, high mechanical flexibility, and selective self-absorbance of the blue part of its fluorescence (FL). While macrocrystals exhibit elasticity, microcrystals deposited at a glass surface behave more like plastic crystals due to significant surface adherence, making them suitable for constructing photonic circuits via micromechanical operation with an atomic-force-microscopy cantilever tip. The flexible crystalline waveguides display optical-path-dependent FL signals at the output termini in both straight and bent configurations, making them appropriate for wavelength-division multiplexing technologies. A reconfigurable 2×2-directional coupler fabricated via micromanipulation by combining two arc-shaped crystals splits the optical signal via evanescent coupling and delivers the signals at two output terminals with different splitting ratios. The presented mechanical micromanipulation technique could also be effectively extended to other flexible crystals.