A chain of π‐stacked molecules in 4‐(2‐chlorophenyl)pyrrolo[1,2‐a]quinoxaline and a hydrogen‐bonded sheet in (4RS)‐4‐(1,3‐1,3‐benzodioxol‐6‐yl)‐4,5‐dihydropyrrolo[1,2‐a]quinoxaline

In the molecule of 4‐(2‐chlorophenyl)pyrrolo[1,2‐a]quinoxaline, C₁₇H₁₁ClN₂, (I), the bond lengths are consistent with electron delocalization in the two outer rings of the fused tricyclic system, with a localized double bond in the central ring. The molecules of (I) are linked into chains by a π–π stacking interaction. In (4RS)‐4‐(1,3‐benzodioxol‐6‐yl)‐4,5‐dihydropyrrolo[1,2‐a]quinoxaline, C₁₈H₁₄N₂O₂, (II), the central ring of the fused tricyclic system adopts a conformation intermediate between screw‐boat and half‐chair forms. A combination of N—H...O and C—H...π(arene) hydrogen bonds links the molecules of (II) into a sheet. Comparisons are made with related compounds.     

Novel combination of non-aqueous capillary electrophoresis and multivariate curve resolution-alternating least squares to determine phenolic acids in virgin olive oil

This paper presents the development of a non-aqueous capillary electrophoresis method coupled to UV detection combined with multivariate curve resolution-alternating least-squares (MCR-ALS) to carry out the resolution and quantitation of a mixture of six phenolic acids in virgin olive oil samples. p-Coumaric, caffeic, ferulic, 3,4-dihydroxyphenylacetic, vanillic and 4-hydroxyphenilacetic acids have been the analytes under study. All of them present different absorption spectra and overlapped time profiles with the olive oil matrix interferences and between them. The modeling strategy involves the building of a single MCR-ALS model composed of matrices augmented in the temporal mode, namely spectra remain invariant while time profiles may change from sample to sample. So MCR-ALS was used to cope with the coeluting interferences, on accounting the second order advantage inherent to this algorithm which, in addition, is able to handle data sets deviating from trilinearity, like the data herein analyzed. The method was firstly applied to resolve standard mixtures of the analytes randomly prepared in 1-propanol and, secondly, in real virgin olive oil samples, getting recovery values near to 100% in all cases. The importance and novelty of this methodology relies on the combination of non-aqueous capillary electrophoresis second-order data and MCR-ALS algorithm which allows performing the resolution of these compounds simplifying the previous sample pretreatment stages.     

Comparison of copper labeling followed by liquid chromatography-inductively coupled plasma mass spectrometry and immunochemical assays for serum hepcidin-25 determination

Hepcidin-25 has been defined as the key biomarker in iron metabolism. This peptide binds to the iron transporter ferroportin to cause its degradation. Therefore, the need for specific, accurate and precise methods for the quantification of hepcidin-25 in biological fluids is dramatically increasing. In this regard, the use of rapid immunochemical methods that provide low limit of quantification is desired for routine clinical use. However, such fast methodologies should be first analytically evaluated and compared with alternative strategies to check for their advantages and limitations. Here we compare the use of a commercial immunochemical assay for hepcidin determination with a novel analytical approach based on Cu-labeling of the peptide followed by Cu determination using liquid chromatography (HPLC) and plasma mass spectrometry (ICP-MS). The figures of merit of both systems reveal similar analytical characteristics and both seem to be adequate for the determination of the peptide at biologically relevant concentrations in human serum samples. The analysis of a larger number of samples (n = 50) by both techniques showed a good agreement in the concentrations found. Such finding permits to address the hepcidin recovery in the sample preparation procedure necessary for the HPLC-ICP-MS analysis in human serum that turn out to be 76–85%. Additionally, limitations due to cross-reactivity issues of the ELISA method could be addressed in some of the samples by using LC-ICP-MS and were confirmed by LC-Electrospray-MS.     

Disposable amperometric magnetoimmunosensor for the sensitive detection of the cardiac biomarker amino-terminal pro-B-type natriuretic peptide in human serum

A novel amperometric magnetoimmunosensor using an indirect competitive format is developed for the sensitive detection of the amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The immunosensor design involves the covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. Accordingly, the target NT-proBNP in the sample and that immobilized on the MBs compete for binding to a fixed amount of the specific HRP-labeled secondary antibody. The immunoconjugate-bearing MBs are captured by a magnet placed under the surface of a disposable gold screen-printed electrode (Au/SPE). The amperometric responses measured at –0.10 V (vs. a Ag pseudo-reference electrode), upon addition of 3,3′,5,5′-tetramethylbenzidine (TMB) as electron transfer mediator and H₂O₂ as the enzyme substrate, are used to monitor the affinity reaction. The developed magnetoimmunosensor provides attractive analytical characteristics in 10-times diluted human serum samples, exhibiting a linear range of clinical usefulness (0.12–42.9 ng mL⁻¹) and a detection limit of 0.02 ng mL⁻¹, which can be used in clinical diagnosis of chronic heart failure in the elderly and for classifying patients at risk of death after heart transplantation. The magnetoimmunosensor was successfully applied to the analysis of spiked human serum samples.     

Comparison of Three Analytical Methods for the Determination of Quinolones in Pig Muscle Samples

This work presents a comparison between three analytical methods developed for the simultaneous determination of eight quinolones regulated by the European Union (marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin, difloxacin, sarafloxacin, oxolinic acid and flumequine) in pig muscle, using liquid chromatography with fluorescence detection (LC–FD), liquid chromatography–mass spectrometry (LC–MS) and liquid chromatography-tandem mass spectrometry (LC–MS/MS). The procedures involve an extraction of the quinolones from the tissues, a step for clean–up and preconcentration of the analytes by solid-phase extraction and a subsequent liquid chromatographic analysis. The limits of detection of the methods ranged from 0.1 to 2.1 ng g⁻¹ using LC–FD, from 0.3 to 1.8 using LC–MS and from 0.2 to 0.3 using LC–MS/MS, while inter- and intra-day variability was under 15 % in all cases. Most of those data are notably lower than the maximum residue limits established by the European Union for quinolones in pig tissues. The methods have been applied for the determination of quinolones in six different commercial pig muscle samples purchased in different supermarkets located in the city of Granada (south-east Spain).

     

Improved Synthesis of Tricyclo (5.2.1.04,10) Decane-2,5,8-Trione by a Pauson-Khand Intramolecular Bis-Annulation

The title compound 1 has been synthesized from diol 3a, either directly or after protection of the two hydroxy groups as benzyl ethers, by an intramolecular Pauson-Khand bis-annulation, followed by catalytic hydrogenation and oxidation in overall yields ranging from 15% (free diol) to 35% (dibenzyl ethers).     

Simple Reduction of Heteroaromatic Esters to Alcohols Using a Sodium Borohydride–Methanol System

Some heteroaromatic esters were reduced to the corresponding alcohols by using a sodium borohydride–methanol system. The reduction was completed within 0.15–2.0 h in refluxing THF. The alcohol products were isolated after aqueous workup in moderate to excellent yield (48–97%).     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.     

New N-Substituted (E)-4-Arylidene Isoquinoline-1,3-dione Derivatives: NMR Spectroscopic Investigation and Antibacterial Activity

Abstract

New N-substituted 4-arylidene-isoquinoline-1,3-dione derivatives were obtained as one geometrical isomer by aldol condensation of the appropriate aldehyde and the corresponding N-substituted homophthalimides. The structural elucidation of compounds 3a–h was established by infrared and NMR spectroscopy including ¹ Dimmock , J. R. ; Wong , M. L. C. Bioactivities and potential uses in drug design of acyclic α,β-unsaturated ketones . Can. J. Pharm. Sci. 1976 , 11 , 35 – 53 .[Web of Science ®] , [Google Scholar]H, ¹³ Perjési , P. ; Szabó , D. ; Batta , G. ; Földesi , A. The stereochemistry of reaction of 2-benzylidenecyclohexanone with dithiocarbamic acid . Tetrahedron Lett. 1987 , 28 , 571 . [Google Scholar]C, CH CORR, and distortionless enhancement by polarization transfer measurements. Compounds 3d–h were evaluated for their antibacterial activity against some strains of bacteria using the disc diffusion method and microdilution tests.     

A Useful Synthesis of Chiral Glyoxylates

A convenient synthesis of the cyclohexyl, (1R,3R,4S)-3-P-menthyl and (15-endo)-2-bomyl glyoxylates, from the respective alcohols and other very available materials, as a model applicable to that of other chiral, sensitive giyoxylates, is described.