Heterocycles [<Emphasis Type="Italic">h</Emphasis>]-fused to 4-oxoquinoline-3-carboxylic acid. Part VII: synthesis of some 6-oxoimidazo[4,5-<Emphasis Type="Italic">h</Emphasis>]quinoline-7-carboxylic acids and esters

Abstract  A series of ethyl 2-(substituted)-9-cyclopropyl-4-fluoro-6-oxo-1H-imidazo[4,5-h]quinoline-7-carboxylates has been prepared from ethyl 7,8-diamino-1,4-dihydroquinoline-3-carboxylate via thermally induced reactions with model alkanoic acids or via microwave-assisted cyclocondensation with some arene carboxaldehydes. Acid-catalysed hydrolysis of the resulting ester derivatives furnished the corresponding imidazoquinoline-7-carboxylic acids. The structures of these new acid and ester derivatives are based on microanalytical and spectral (IR, MS, and NMR) data. Graphical abstract        

Electrospray mass spectrometry analysis of dendritic branches bearing peripheral fullerene subunits

The electrospray mass spectrometric characterization of neutral dendrons with a carboxylic acid function or a t-butyl ester moiety at the central point and up to eight peripheral C₆₀ subunits has been performed and is described in detail. Molecules bearing a carboxylic acid group at the center turned out to be preferentially ionized by deprotonation, whereas those with a t-butyl ester head group were ionized by reduction of the C₆₀ units in the infusion capillary of the electrospray source. Electronic supplementary material Supplementary material is available for this article at and is accessible for authorized users.     

Determination of total <Emphasis Type="Italic">trans</Emphasis> fats and oils by infrared spectroscopy for regulatory compliance

The mandatory requirement in many countries to declare the amount of trans fat present in food products and dietary supplements has led to a need for sensitive and accurate methodologies for the rapid quantitation of total trans fats and oils. Capillary gas chromatography (GC) and infrared spectroscopy (IR) are the two methods most commonly used to identify and quantify trans fatty acids for food labeling purposes (see the article by Delmonte and Rader in this ABC issue for a detailed presentation of GC methodology). The present article provides a comprehensive review of the IR technique and the current attenuated total reflection (ATR) Fourier-transform (FT) IR methodologies for the rapid determination of total trans fats and oils. This review also addresses potential sources of interferences and inaccuracies in FTIR determinations, particularly those done at low trans levels. Recent observations have shown that the presence of saturated fats caused interferences in the FTIR spectra observed for trans triacylglycerols. The recognition and resolution of previously unresolved quantitative issues improved the accuracy and sensitivity of the FTIR methodology. Once validated, it is anticipated that the new negative second-derivative ATR-FTIR procedure will make IR spectroscopy more suitable than ever, and a rapid alternative and/or complementary method to GC, for the rapid determination of total trans fats for regulatory compliance. Figure Infrared light bouncing inside an internal reflection crystal     

Enantioselective complexation of carbamoylated quinine and quinidine with <Emphasis Type="Italic">N</Emphasis>-blocked amino acids: vibrational and electronic circular dichroism study

Infrared absorption (IR) and vibrational and electronic circular dichroism (VCD and ECD, respectively) spectra of tert-butylcarbamoylquinine (t-BuCQN) and pseudoenantiomeric tert-butylcarbamoylquinidine (t-BuCQD), denoted as selectors (SO), complexed with chiral (S) and (R)-3,5-dinitrobenzoylleucine (DNB-Leu) and achiral 3,5-dinitrobenzoylglycine (DNB-Gly), denoted as selectands (SA), in methanol and acetonitrile, with the spectra of pure SA and SO are reported. H–D exchange of exchangeable hydrogen atoms of SA and SO in deuterated methanol which occurs in IR and VCD experiments is exploited to identify Amide II and Amide III vibrational modes. The formation of preferentially bound complexes composed of sterically compatible combinations of DNB-Leu and SO are manifested by increased intensity of VCD bands assigned to vibrations of amide, carbamate, quinoline, and dissociated carboxylate group and also by increased ECD signals. The VCD technique revealed similarities between the strongly bound diastereomeric complex of chiral DNB-Leu and SO and the complex of achiral DNB-Gly and SO, highlighting the leading role of SO in the formation of SA–SO complex. Figure Vibrational circular dichroism study: Interaction markers typical of the binding between the quinine selector and the derivatized amino acid selectand     

In vitro and in vivo metabolisms of K-48

Metabolic pathways of the oxime K-48 have been elucidated by means of in vitro and in vivo experiments. K-48 exposure to rat liver microsomal fraction resulted in the formation of a hydroxylated derivative, in addition to a small molecular fragment. The in vivo metabolism in rats was investigated after intramuscular administration of 50 μmol oxime. K-48 was present in the rat serum in unchanged form. Similarly, the analysis of rat cerebrospinal fluid indicated the sole occurrence of unchanged K-48. In contrast, unchanged K-48 was not found in the rat urine, where only the metabolite generated by epoxidation on the alkyl chain connecting the two pyridinium rings was present. The presence of unchanged K-48 in the serum and cerebrospinal fluid facilitates quantitative determination using HPLC separation and ultraviolet absorbance detection. Figure Suggested metabolic pathways of K-48     

Efficient conversion of aldoximes to nitriles using phosphoric acid diethyl ester 2-phenylbenzimidazol-1-yl ester

Abstract  Aromatic aldoximes were converted to the corresponding nitriles in good to excellent yields by employing phosphoric acid diethyl ester 2-phenylbenzimidazol-1-yl ester as reagent. The method was equally effective for oximes bearing electron-donating and electron-withdrawing substituents. Graphical Abstract        

DNA biosensors for the detection of aflatoxin producing <Emphasis Type="Italic">Aspergillus flavus</Emphasis> and <Emphasis Type="Italic">A. parasiticus</Emphasis>

Abstract  In this work, we report on the development of a DNA-based piezoelectric biosensor specific for the detection of an amplicon of the aflD gene of Aspergillus flavus and A. parasiticus. Expression of this gene is consistently correlated with a strain’s ability to produce aflatoxins that are considered very potent liver carcinogens in various animal species and humans. The DNA biosensor has been characterized with synthetic oligonucleotides and amplicons. Moreover, it has been applied to the analysis of real samples consisting of amplicons of DNA extracted from flours and feed contaminated with A. flavus and A. parasiticus. Graphical Abstract        

Elucidation of n-butyl benzyl phthalate biodegradation using high-performance liquid chromatography and gas chromatography–mass spectrometry

n-Butyl benzyl phthalate (BBP) is an endocrine-disrupting chemical. A bacterium species capable of using BBP as the sole source of carbon and energy was isolated from mangrove sediment. Effects of BBP concentration, pH, temperature, and salinity on BBP biodegradation were studied. The optimum pH, temperature, and salinity for the BBP biodegradation were 7.0, 37°C, and 15 g L⁻¹, respectively. BBP was completely degraded within 6 days under optimum conditions, and the biodegradation of BBP could be fitted to a first-order kinetic model. The major metabolites of BBP biodegradation were identified as mono-butyl phthalate, mono-benzyl phthalate, phthalic acid, and benzoic acid by using high-performance liquid chromatography and gas chromatography–mass spectrometry. A preliminary metabolic pathway was proposed for the biodegradation of BBP.      

Synthesis and biological activity of (Z) and (E) isomers of 3-(3,4-diaryl-1,2,4-triazole-5-yl)prop-2-enoic acid

Abstract  (Z)-3-(3,4-diaryl-1,2,4-triazole-5-yl)prop-2-enoic acid derivatives were obtained in the course of the reaction of N ³-substituted amidrazones with maleic anhydride, and isomerized into the (E) isomers by heating under reflux in acetic acid solution. The molecular structure of the compounds obtained was confirmed by IR and ¹H NMR spectroscopy, and by X-ray crystallography for (2E)-3-(4,5-diphenyl-4H-1,2,4-triazol-3-yl)prop-2-enoic acid. The antiviral and immunomodulating activity of several of the compounds was examined. Graphical abstract        

Derivatization of organophosphorus nerve agent degradation products for gas chromatography with ICPMS and TOF-MS detection

Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC–ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N-methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC–time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC–ICPMS. Figure Illustrated here are six parent organophosphorus nerve agents corresponding to the degradation products analyzed by gas chromatography with ICPMS and ToF-MS detection. The authors would like to thank Daisy-Malloy Hamburg and Kevin M. Kubachka for creating this figure     

Liquid chromatography–electrospray tandem mass spectrometry investigations of fragmentation pathways of biliary 4,4′-methylenedianiline conjugates produced in rats

4,4′-methylenedianiline (DAPM) is the main building block for production of 4,4′-methylenediphenyldiisocyanate that has been widely used in the manufacturing of polyurethane materials including medical devices. Although it was revealed that damage to biliary epithelial cells of the liver and common bile duct occurred upon acute exposure to DAPM, the exact mechanism of DAPM toxicity is not fully understood. Both phase I and II biotransformations of DAPM, some of which generate reactive intermediates, are characterized in detail by liquid chromatography electrospray tandem mass spectrometry. The two most prominent metabolites found in rat bile (M2 and M7) implicated glutathione, glucuronic acid, and glycine conjugations (phase II) following hydroxylation, and N-oxidation (phase I). Their decomposition pathways, as evidenced by MS ⁿ experiments, have been elucidated in detail. Figure Proposed fragmentation pathways of a DAPM metabolite     

Evaluation of quantum dots applied as switchable layer in a light-controlled electrochemical sensor

Gold electrodes with switchable conductance are created by coating the gold surface with different colloidal quantum dots. For the quantum dot immobilization, a dithiol compound was used. By polarizing the electrode and applying a light pointer, local photocurrents were generated. The performance of this setup was characterized for a variety of different nanoparticle materials regarding drift and signal-to-noise ratio. We varied the following parameters: quantum dot materials and immobilization protocol. The results indicate that the performance of the sensor strongly depends on how the quantum dots are bound to the gold electrode. The best results were obtained by inclusion of an additional polyelectrolyte film, which had been fabricated using layer-by-layer assembly.      

Intensified biochip system using chemiluminescence for the detection of Bacillus globigii spores

This paper reports the first intensified biochip system for chemiluminescence detection and the feasibility of using this system for the analysis of biological warfare agents is demonstrated. An enzyme-linked immunosorbent assay targeting Bacillus globigii spores, a surrogate species for Bacillus anthracis, using a chemiluminescent alkaline phosphatase substrate is combined with a compact intensified biochip detection system. The enzymatic amplification was found to be an attractive method for detection of low spore concentrations when combined with the intensified biochip device. This system was capable of detecting approximately 1 × 10⁵ Bacillus globigii spores. Moreover, the chemiluminescence method, combined with the self-contained biochip design, allows for a simple, compact system that does not require laser excitation and is readily adaptable to field use. Figure Schematic diagram of the miniature biochip detection system     

Prediction of retention times of polycyclic aromatic hydrocarbons and <Emphasis Type="Italic">n</Emphasis>-alkanes in temperature-programmed gas chromatography

We have developed an iterative procedure for predicting the retention times of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes during separations by temperature-programmed gas chromatography. The procedure is based on estimates of two thermodynamic properties for each analyte (the differences in enthalpy and entropy associated with movements between the stationary and mobile phases) derived from data acquired experimentally in separations under isothermal conditions at temperatures spanning the range covered by the temperature programs in ten-degree increments. The columns used for this purpose were capillary columns containing polydimethylsiloxane-based stationary phases with three degrees of phenyl substitution (0%, 5%, and 50%). Predicted values were mostly within 1% of experimentally determined values, implying that the method is stable and precise. Figure Predicted values were mostly within 1 % of experimentally determined values, thus implying that the method is stable and precise     

Analysis of biosensors by chemically specific optical techniques. Chemiluminescence-imaging and infrared spectroscopic mapping ellipsometry

The standard methods currently used to read out microarrays are fluorescent and chemiluminesent imaging techniques. These methods require labeling of a component with a marker and, usually, only the concentration of the marker molecule is detected. A label-free imaging method that also enables quantitative spectroscopic analysis of the composition and component interaction would be of great advantage. In this article it is shown for the first time that IR mapping ellipsometry enables label-free imaging of a biochip before and after incubation with peptide solution. The measurements prove that IR ellipsometry is a sensitive tool for laterally resolved identification of the different materials and determination of the composition of a biochip. The lateral resolution required was achieved by using radiation from an infrared synchrotron beamline.      

Different iron-chelating properties of pyochelin diastereoisomers revealed by LC/MS

Pyochelin is a siderophore and virulence factor common to Burkholderia cepacia and several Pseudomonas strains. It is isolated from bacterial media as a mixture of two epimers, which readily equilibrate in most solvents. Experiments based on high-performance liquid chromatography/electrospray ionization mass spectrometry are reported here, allowing the investigation of the different Fe(III)-chelating properties of pyochelin diastereomers in solution without the need for labourious isolation. It is demonstrated in this study that only one of the two pyochelin diastereomers is able to chelate Fe(III); no Fe(III) complexes of the other diastereomer could be detected. The Fe(III)–pyochelin complex exhibited a 1:1 metal-to-siderophore ratio and no evidence for other stoichiometries was found.      

Headspace mass spectrometry methodology: application to oil spill identification in soils

In the present work we report the results obtained with a methodology based on direct coupling of a headspace generator to a mass spectrometer for the identification of different types of petroleum crudes in polluted soils. With no prior treatment, the samples are subjected to the headspace generation process and the volatiles generated are introduced directly into the mass spectrometer, thereby obtaining a fingerprint of volatiles in the sample analysed. The mass spectrum corresponding to the mass/charge ratios (m/z) contains the information related to the composition of the headspace and is used as the analytical signal for the characterization of the samples. The signals obtained for the different samples were treated by chemometric techniques to obtain the desired information. The main advantage of the proposed methodology is that no prior chromatographic separation and no sample manipulation are required. The method is rapid, simple and, in view of the results, highly promising for the implementation of a new approach for oil spill identification in soils. Figure PCA score plots illustrate clear discrimination of types of crude oil in polluted soil samples (e.g. results are shown for vertisol)     

<Superscript>13</Superscript>C-labeled bilirubin: synthesis of 3<Superscript>1</Superscript>(3<Superscript>2</Superscript>),17<Superscript>1</Superscript>(17<Superscript>2</Superscript>)-di-[<Superscript>13</Superscript>C]-mesobilirubin-XIIIα

Abstract  The title compound, labeled with ¹³C in the ethyl groups was synthesized from K¹³CN and low-molecular-weight components. The synthetic relay compound was 3¹(3²)[¹³C]-xanthobilirubinic acid methyl ester in a synthetic route that leads to a label in the ethyl β-substituent of a dipyrrinone model for bilirubin. This labeled dipyrrinone was oxidatively coupled to the dimethyl ester of mesobiliverdin-XIIIα, thereby providing a route to a ¹³C-labeled mesobiliverdin and mesobilirubin, with one carbon of each ethyl being 98% ¹³C-enriched. Graphical Abstract        

Synthesis and serotonin antagonist and antianexity activities of pyrrolidine derivatives from 4-hydrazinyl-1-p-substituted phenyl-2,5-dihydro-1H-pyrrole-3-carbonitriles

Abstract   N-(p-substituted phenyl)-4-cyanopyrrolidin-3-ones and their corresponding hydrazines were prepared and used as starting materials to synthesize heterocyclic candidates as serotonin antagonist and antianexity agents. Condensation of hydrazines with selected aromatic aldehydes afforded the corresponding Schiff bases. The hydrazines were treated with phenyl isothiocyanate to afford the corresponding thiosemicarbazides, which were cyclized with ethyl bromoacetate to N-phenylthiazolidinones. The hydrazine was reacted with 1,2,4,5-tetrachlorophthalic anhydride to give the tetrachloroimide derivative. It was reacted with benzoyl acetonitrile, 2-(bismethylsulfanyl-methylene)malononitrile, 2-ethoxymethylenemalononitrile, or 2-cyano-3-ethoxyacrylic acid ethyl ester to afford the corresponding pyrazoline derivatives. Schiff bases were obtained by simple condensation of the hydrazine with different carbonyl compounds. All the compounds were screened for their serotonin antagonistic and antianexity activities, and they showed high activities compared to buspirone and diazepam as controls. Graphical abstract        

Determining sulfamonomethoxine and its acetyl/hydroxyl metabolites in chicken plasma under organic solvent-free conditions

A quantitative technique is described for a sample preparation followed by high performance liquid chromatography method for the simultaneous determination of sulfamonomethoxine and its metabolites, N ⁴-acetyl SMM and 2,6-dihydroxy SMM, in chicken plasma. The average recoveries, analytical total time, and limits of quantitation were ≥80% (relative standard deviations (SD) ≤6%), <30 min sample-1 (12 samples in 2 h), and ≤0.09 μg ml⁻¹, respectively. The procedure, performed under 100% aqueous conditions, uses no organic solvents and toxic reagents at all and is, therefore, harmless to the environment and humans.