Spiro[1,3-benzoxathiepin-4(5H),1′-cyclohexa[2,4]dien]-2,2′-dione,a Novel Heterocyclic Ring System

Abstract

Besides the common cyclisation reactions between divalent electrophiles such as Soc1₂, SC1₂, etc. and 2,2′-alkylidene-bisphenols 1 with selective attack by the two oxygens yielding dibenzo[d,g][1,3,2]dioxathiocines [1] we observed previously an unusual cyclisation of 1 with S₂CI₂ with a nucleophilic attack by the ortho- and para-carbon atoms (C(2) and C(4)) of bisphenol 1 [2]. We now report a new type of cyclocondensation reaction of 4,4′,6,6′-tetrasubstituted 2,2′-alkylidene-bisphenols 1 with ClSCOCl affording spiro[1,3-benzoxathiepin-4(5H),1′-cyclohexa[2,4]dien]-2,2′-diones 2 together with the cyclic carbonates 3. The structures of the products were elucidated mainly by ^l3C-NMR- and ¹H-NMR-spectroscopy. The mode of formation of the novel spiro thiocarbonates 2 resp. the known carbonates 3 [3] is discussed.     

Complexation and Transport of Alkali and Alkaline Earth Metal Cations by p-tert-Butyldihomooxacalix[4]arene Tetraketone Derivatives

The binding properties of three p-tert-butyldihomooxacalix[4]arene tetraketone derivatives (tert-butyl 2b, adamantyl 2c and phenyl 2d) in the cone conformation and one derivative (methyl 2a) in a partial cone conformation, towards alkali and alkaline earth metal cations have been established by extraction studies of metal picrates from water into dichloromethane, stability constant measurements in methanol and acetonitrile, and by ¹H NMR spectrometry. Transport experiments of metal picrates through a dichloromethane membrane were also performed. The results are compared to those obtained with closely-related calix[n]arene derivatives (n = 4 and 5) and discussed in terms of the substituents, size and conformational effects. Methylketone 2a is a poor binder for all the cations studied, due to its partial cone conformation. Ketones 2b, 2c and 2d show high extraction and complexation levels for the alkali cations, with similar profiles and preference for K⁺ and Na⁺ (plateau selectivity). Towards alkaline earth cations, these ketones show a strong peak selectivity for Ba²⁺ in extraction, but a plateau selectivity for Ca²⁺, Sr²⁺ and Ba²⁺ in complexation. The nature of the substituent attached to the ketone function has some influence on their binding properties, with phenylketone 2d being a slightly weaker binder than ketones 2b and 2c. ¹H NMR titrations confirm the formation of 1:1 complexes between the ketones and the cations studied, also indicating that they should be located inside the cavity defined by the phenoxy and carbonyl oxygen atoms. Ketones 2b, 2c and 2d show transport rates that do not follow, in general, the same trends observed in extraction and complexation.     

Instrumental Dependent Dissociations of n-Propyl/Isopropyl Phosphonate Isomers: Evaluation of Resonant and Non-Resonant Vibrational Activations

Structural elucidation and distinction of isomeric neurotoxic agents remain a challenge. Tandem mass spectrometry can be used for this purpose in particular if a “diagnostic” product ion is observed. Different vibrational activation methods were investigated to enhance formation of diagnostic ions through consecutive processes from O,O-dialkyl alkylphosphonates. Resonant and non-resonant collisional activation and infrared multiphoton dissociation (IRMPD) were used with different mass spectrometers: a hybrid quadrupole Fourier transform ion cyclotron resonance (Qh-FTICR) and a hybrid linear ion trap-Orbitrap (LTQ/Orbitrap). Double resonance (DR) experiments, in ion cyclotron resonance (ICR) cell, were used for unambiguous determination of direct intermediate yielding diagnostic ions. From protonated n-propyl and isopropyl O-O-dialkyl-phosphonates, a diagnostic m/z 83 ion characterizes the isopropyl isomer. This ion is produced through consecutive dissociation processes. Conditions to favor its formation and observation using different activation methods were investigated. It was shown that with the LTQ, consecutive experimental steps of isolation/activation with modified trapping conditions limiting the low mass cut off (LMCO) effect were required, whereas with FT-ICR by CID and IRMPD the diagnostic ion detection was provided only by one activation step. Among the different investigated activation methods it was shown that by using low-pressure conditions or using non-resonant methods, efficient and fast differentiation of isomeric neurotoxic agents was obtained. This work constitutes a unique comparison of different activation modes for distinction of isomers showing the instrumental dependence characteristic of the consecutive processes. New insights in the dissociation pathways were obtained based on double-resonance IRMPD experiments using a FT-ICR instrument with limitation at low mass values.

Development and optimization of the determination of pharmaceuticals in water samples by SPE and HPLC with diode‐array detection

This paper describes the development, optimization, and validation of a method for the determination of five pharmaceuticals from different therapeutic classes (antibiotics, anthelmintics, glucocorticoides) in water samples. Water samples were prepared using SPE and extracts were analyzed by HPLC with diode‐array detection. The efficiency of 11 different SPE cartridges to extract the investigated compounds from water was tested in preliminary experiments. Then, the pH of the water sample, elution solvent, and sorbent mass were optimized. Except for optimization of the SPE procedure, selection of the optimal HPLC column with different stationary phases from different manufacturers has been performed. The developed method was validated using spring water samples spiked with appropriate concentrations of pharmaceuticals. Good linearity was obtained in the range of 2.4–200 μg/L, depending on the pharmaceutical with the correlation coefficients >0.9930 in all cases, except for ciprofloxacin (0.9866). Also, the method has revealed that low LODs (0.7–3.9 μg/L), good precision (intra‐ and interday) with RSD below 17% and recoveries above 98% for all pharmaceuticals. The method has been successfully applied to the analysis of production wastewater samples from the pharmaceutical industry.     

Carbon and nitrogen isotope analysis of atrazine and desethylatrazine at sub-microgram per liter concentrations in groundwater

Environmental degradation of organic micropollutants is difficult to monitor due to their diffuse and ubiquitous input. Current approaches—concentration measurements over time, or daughter-to-parent compound ratios—may fall short, because they do not consider dilution, compound-specific sorption characteristics or alternative degradation pathways. Compound-specific isotope analysis (CSIA) offers an alternative approach based on evidence from isotope values. Until now, however, the relatively high limits for precise isotope analysis by gas chromatography—isotope ratio mass spectrometry (GC-IRMS) have impeded CSIA of sub-microgram-per-liter scale micropollutant concentrations in field samples. This study presents the first measurements of C and N isotope ratios of the herbicide atrazine and its metabolite desethylatrazine at concentrations of 100 to 1,000 ng/L in natural groundwater samples. Solid-phase extraction and preparative HPLC were tested and validated for preconcentration and cleanup of groundwater samples of up to 10 L without bias by isotope effects. Matrix interferences after solid-phase extraction could be greatly reduced by a preparative HPLC cleanup step prior to GC-IRMS analysis. Sensitivity was increased by a factor of 6 to 8 by changing the injection method from large-volume to cold-on-column injection on the GC-IRMS system. Carbon and nitrogen isotope values of field samples showed no obvious correlation with concentrations or desethylatrazine-to-atrazine ratios. Contrary to expectations, however, δ ¹³ C values of desethylatrazine were consistently less negative than those of atrazine from the same sites. Potentially, this line of evidence may contain information about further desethylatrazine degradation. In such a case, the common practice of using desethylatrazine-to-atrazine ratios would underestimate natural atrazine degradation.     

Mass spectrometric profiling of Bacillus cereus strains and quantitation of the emetic toxin cereulide by means of stable isotope dilution analysis and HEp-2 bioassay

A fast and robust high-throughput ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC–TOF MS) profiling method was developed and successfully applied to discriminate a total of 78 Bacillus cereus strains into no/low, medium and high producers of the emetic toxin cereulide. The data obtained by UPLC–TOF MS profiling were confirmed by absolute quantitation of cereulide in selected samples by means of high-performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) and stable isotope dilution assay (SIDA). Interestingly, the B. cereus strains isolated from four vomit samples and five faeces samples from patients showing symptoms of intoxication were among the group of medium or high producers. Comparison of HEp-2 bioassay data with those determined by means of mass spectrometry showed differences, most likely because the HEp-2 bioassay is based on the toxic action of cereulide towards mitochondria of eukaryotic cells rather than on a direct measurement of the toxin. In conclusion, the UPLC–electrospray ionization (ESI)–TOF MS and the HPLC–ESI–MS/MS–SIDA analyses seem to be promising tools for the robust high-throughput analysis of cereulide in B. cereus cultures, foods and other biological samples.

Development of a nanocomposite system and its application in biosensors construction

The present work describes the development of a nanocomposite system and its application in construction of a new amperometric biosensor applied in the determination of total polyphenolic content from propolis extracts. The nanocomposite system was based on covalent immobilization of laccase on functionalized indium tin oxide nanoparticles and it was morphologically and structural characterized. The casting of the developed nanocomposite system on the surface of a screen-printed electrode was used for biosensor fabrication. The analytical performance characteristics of the settled biosensor were determined for rosmarinic acid, caffeic acid and catechol (as laccase specific substrate). The linearity was obtained in the range of 1.06×10^?6 ? 1.50×10^?5 mol L^?1 for rosmarinic acid, 1.90×10^?7 ? 2.80×10^?6 mol L^?1 for caffeic acid and 1.66×10^?6 ? 7.00×10^?6 mol L^?1 for catechol. A good sensitivity of amperometric biosensor 141.15 nA µmol^?1 L^?1 and fair detection limit 7.08×10^?8 mol L^?1 were obtained for caffeic acid. The results obtained for polyphenolic content of propolis extracts were compared with the chromatographic data obtained by liquid-chromatography with diode array detection.