Metabolite identification by data-dependent accurate mass spectrometric analysis at resolving power of 60,000 in external calibration mode using an LTQ/Orbitrap

Performance evaluation of accurate mass measurement by the LTQ/Orbitrap, at a resolving power of 60,000 and in external calibration mode, indicated that the Orbitrap is capable of providing high mass accuracy of <2 ppm for over 24 h post-calibration. This, together with limited trade-off between sensitivity and resolving power plus a wide dynamic range for mass accuracy, suggested that the LTQ/Orbitrap is an ideal analytical tool for structural elucidation of metabolites. The application of the LTQ/Orbitrap to identification of human liver microsomal metabolites of carvedilol was evaluated, using parent mass list triggered data-dependent multiple-stage accurate mass analysis, at a resolving power of 60,000 in external calibration mode. A metabolite identification workflow was developed to utilize chemical formulas from high-resolution accurate mass measurements to confirm structures of product ions of a drug proposed by Mass Frontier, illustrated by identification of structures used to establish lineage of product ions of carvedilol, which later served as a template for identification of its metabolites. A total of 58 in vitro metabolites of carvedilol were detected using 5-ppm mass tolerance filters for theoretical m/z of protonated molecules of predicted metabolites in addition to product ions and neutral mass losses diagnostic of carvedilol. The chemical formulas with unsaturation numbers calculated from the accurate m/z of precursor and product ions can be used to assign, with a high degree of confidence, the structures of metabolites and the sites of metabolism. The mass accuracies obtained for all full scan MS and MSn spectra were <2 ppm. The majority of the metabolites identified agreed with those previously reported except for those that have not been reported before. For example, several glutathione conjugates of carvedilol were reported for the first time, which may explain the reported hepatotoxicity during clinical trials and recent clinical use.     

Selective solar photocatalytic oxidation of ethylbenzene on C,N, and S doped TiO<Subscript>2</Subscript>

The liquid-phase photo-oxidation of ethylbenzene (EB) is investigated in solar light with air/O₂/N₂ at atmospheric pressure, in a batch reactor using acetonitrile medium. It is carried out over TiO₂ doped with C, N, and S (TCNS) photocatalyst samples. The photocatalytic oxidation yielded acetophenone (33%) and 1-phenylethanol (21%) at 56% conversion of EB during a 6-h irradiation time. This product distribution indicates that C–H bond activation has occurred only at the alkyl chain. The effects of the EB to water content ratio, amount of photocatalyst and its sustainability, pH, have been studied. It is illustrated that the reaction carried out by this environmentally friendly photocatalysis is truly heterogeneous under mild conditions using solar light and no waste generation. An optimum loading of TCNS5 was observed for the photo-oxidation of EB.     

Solubility Behavior of Lornoxicam in Binary Solvents of Pharmaceutical Interest

The solubility behavior of lornoxicam was studied in binary solvent systems. Solutions containing an excess of drug were shaken for 72?h at 25?°C, filtered and analyzed. To understand the solute?Csolvent interactions, ideal, Hildebrand?CScatchard and extended Hildebrand solubility approaches were used. The ideal solubility of lornoxicam was calculated from the enthalpy of fusion. The molar enthalpy of fusion was obtained from DSC studies. The experimental mole fraction solubility deviated from the ideal mole fraction solubility, indicating self-association of solute, or solvent, or both in solution. The solubility behavior failed to satisfy the Hildebrand?CScatchard equations. The solubilities of lornoxicam were back calculated with an interaction energy term ??W?? and a rational activity coefficient term ??(log₁₀ ?? ₂)/A??. These parameters were regressed against a polynomial function of ?? ₁, the solubility parameter of the solvent mixture. The solubility behavior of lornoxicam obeyed the extended Hildebrand equation. The solubility parameter of lornoxicam ?? ₂ was found to be 27 MPa^1/2.     

Design and Optimization of Ecofriendly One-Pot Synthesis of 2,4,5-Triaryl-1H-imidazoles by Three-Component Condensation Using Response Surface Methodology

Phase-transfer-catalyzed, highly versatile, and high-yielding protocol for the synthesis of 2,4,5-triaryl-1H-imidazoles was developed through response surface methodology (RSM). The effects of different solvents, reaction paths, and phase-transfer catalysts (PTCs) in different concentrations were envisioned. Three independent variables (catalyst, catalyst loading, and solvent volume) identified by one-factor-at-a-time (OFAT) study were screened through full factorial design at two levels. The analysis of variance results suggested the significance of catalyst PEG400 and solvent glacial acetic acid at 5 h reaction. The optimum reaction conditions suggested by the RSM were the use of PEG400 (10.61 mol%) and glacial acetic acid (10.71 mL) for 5 h cycloocondensation. The experimental yield of 4,5-diphenyl-2-nitrophenyl-1H-imidazole (97%) was in agreement with predicted yield (97.5%).     

Effect of thermo-physical properties on turbulent film boiling

Turbulent film boiling from a vertical surface is theoretically investigated considering the properties as functions of the temperature. The proposed analytical model is tested making use of the experimental data available in the literature for liquid nitrogen. It is observed that a satisfactory agreement is found between the theory and the experimental data. A new correlation for the prediction of heat transfer coefficients under film boiling conditions is presented.Das turbulente Filmsieden an einer senkrechten Fläche wird unter Berücksichtigung temperaturabhängiger Stoffwerte theoretisch untersucht. Eine Überprüfung des vorgeschlagenen analytischen Modells erfolgt mit Hilfe von in der Literatur greifbaren experimentellen Daten für flüssigen Stickstoff, wobei befriedigende Übereinstimmung zwischen Theorie und Versuchsdaten festgestellt werden konnte. Ferner wird eine neue Korrelationsbeziehung für die Vorausberechnung der Wärmeübergangskoeffizienten unter Filmsiedebedingungen angegeben.     

Remarks on a nonlinear complementarity problem

A class of nonlinear complementarity problems defined by monotone operators is considered in the spaceL _p [a,b], and an existence theorem is established using Tarski's fixed-point theorem.     

Determination of antimony in lead, zinc concentrates and other smelter products by atomic-absorption spectrophotometry after separation by n-butyl acetate extraction of the chloro-complex

An extractive atomic-absorption spectrophotometric (AAS) procedure is developed for fast and accurate determination of up to 20 mug/g antimony in lead and zinc concentrates and other smelter products. The procedure involves digestion of the sample with potassium bisulphate and sulphuric acid, addition of hydrazine to reduce all antimony to Sb(III), reoxidation to Sb(V), extraction of the chloro-complex of antimony(V) with n-butyl acetate, and AAS analysis of the organic phase for antimony.     

Conformations of dibenzylideneacetone: An IR spectroscopic study

The conformational analysis of dibenzylideneacetone has been carried out using IR spectroscopy. Appearance of a triplet C=O band is attributed to the coexistence of three conformers viz s-cis, cis, s-cis, trans and nonplanar s-trans, trans in contrast to the earlier findings which showed the existence of only two conformers. The relative proportions of the conformers are in the order s-cis, trans> nonplanar s-trans, trans> s-cis, cis in less polar solvents and nonplanar s-trans, trans> s-cis, trans> s-cis, cis in more polar solvents.     

The structures of lignans from Gmelina arborea Linn

Five new lignans isolated from Gmelina arborea Linn have been characterised. The parent compound arboreol, is 2a,6e-dipiperonyl-1e,2e-dihydroxy-3,7-dioxabicyclo-[3,3,0]-octane. It is accompanied by its 2-O-methyl ether, the 2-O-ethyl ether and its 2-epimer, isoarboreol,. The fifth substance, gmelanone, is the first reported example of a lignan derived from 3,6-dioxabicyclo-[3,2,1]-octane.     

The direct production of monoisopinocampheylborane by the redistribution of diisopinocampheylborane with borane

Two simple and direct methods are outlined for the production of monoisopinocampheylphenylborane, a valuable chiral hydroborating agent.