Intermediates in the reduction of the antituberculosis drug PA-824, (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine, in aqueous solution

The reduction chemistry of the new anti-tuberculosis drug PA-824, together with a more water-soluble analogue, have been investigated using pulse and steady-state radiolysis in aqueous solution. Stepwise reduction of these nitroimidazo-dihydrooxazine compounds through electron transfer from the CO(2) (-) species revealed that, unlike related nitroimidazoles, 2-electron addition resulted in the reduction of the imidazole ring in preference to the nitro group. In mildly acidic solution a nitrodihydroimidazo intermediate was formed, which was reduced further to the amine product. In both alkaline and neutral solution, an intermediate produced on 2-electron reduction was resistant to further reduction and reverted to parent compound on extraction or mass spectrometric analysis of the solution. The unusual reduction chemistry of these nitroimidazole compounds, exhibiting ring over nitro group reduction, is associated with alkoxy substitution in the 2-position of a 4-nitroimidazole. The unique properties of the intermediates formed on the reduction of PA-824 need to be considered as playing a possible role in its bactericidal action.     

Highly asymmetric coordination of trimethylsilyl groups to tetrazole and triazole rings: an experimental and computational study in gaseous and crystalline phases

1-Trimethylsilyltetrazole, 1, has been synthesised from chlorotrimethylsilane and tetrazole in the presence of triethylamine as an auxiliary base. The structure of this compound has been determined in the crystalline phase by X-ray diffraction of a crystal grown in situ. The gas-phase structures of 1 and 1-trimethylsilyl-1,2,4-triazole, 2, have been determined by gas-phase electron diffraction (GED). An extensive investigation of these and related compounds by ab initio calculations is also reported. The angles between the rings and the substituents on N were of particular interest. It was found that the calculated difference of 15.5 degrees between the CNSi and NNSi angles in 1 was mostly, but not entirely, an inherent property of the tetrazole ring and not due to a short SiN interaction.     

Folate content in sea buckthorn berries and related products (Hippophaë rhamnoides L. ssp. rhamnoides): LC-MS/MS determination of folate vitamer stability influenced by processing and storage assessed by stable isotope dilution assay

A stable isotope dilution assay was adopted for quantitation of folate vitamers in sea buckthorn berries, juice, and concentrate using fourfold labeled folate isotopologues of the folate derivatives as the internal standards and reversed-phase liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI-MS/MS). Processing effects and storage stability were investigated during juice and concentrate production from sea buckthorn berries (Hippopha? rhamnoides). The technological processing of the berries caused a total degradation of tetrahydrofolate and 5-formyltetrahydrofolate in the generated juice. The content of the main folate vitamer 5-methyltetrahydrofolate remained approximately unchanged during the whole processing from the berries to the concentrate. Sea buckthorn juice was stored under two household storage conditions (6 degrees C, 25 degrees C), and also under accelerated aging conditions (40 degrees C) for up to 7 days to determine the effects of storage temperature on the stability of 5-methyltetrahydrofolate. The content of 5-methyltetrahydrofolate was nearly unchanged during the storage at 6 degrees C after 7 days. The juice showed almost identical degradation of 5-methyltetrahydrofolate of about 17-20% at 25 degrees C and 40 degrees C after 7 days of storage. [figure: see text]     

Surface properties of a series of amphiphilic dendrimers with short hydrophobic chains

A series of tree-shaped, amphiphilic dendrimers was synthesized. The products belong to the family of one-directional arborols of the form ([9]-n), where the notation signifies that each molecule has nine hydroxyl groups ([9]-) as the hydrophilic head and an alkyl chain as the hydrophobic moiety (n = 6, 8, or 10 carbon atoms). The surfactant character changes dramatically as the number of methylene groups increases. The critical micelle concentration of [9]-6 was determined, and pressure-area isotherms of the less soluble [9]-8 and [9]-10 were obtained. Large structures existed atop the spread layers. Large structures were also found in solutions of [9]-6.     

A simple Cu-catalyzed coupling approach to substituted 3-pyridinol and 5-pyrimidinol antioxidants

A convenient approach to 3-pyridinols and 5-pyrimidinols via a two-step Cu-catalyzed benzyloxylation/catalytic hydrogenation sequence is presented. The corresponding 3-pyridinamines and 5-pyrimidinamines can be prepared in an analogous sequence utilizing benzylamine in lieu of benzyl alcohol. The radical-scavenging ability of these derivatives are preliminarily explored and reveal that the increased acidities of the pyridinols and pyrimidinols render them susceptible to more significant kinetic solvent effects when compared to phenols.     

Selective determination of acidic pharmaceuticals in wastewater using molecularly imprinted solid-phase extraction

The determination of acidic pharmaceuticals, such as non-steroidal anti-inflammatory drugs NSAIDs and clofibric acid (metabolite of clofibrate), at low ng L⁻¹ levels in wastewater requires highly selective and sensitive analytical procedures. The removal of matrix components during sample preparation results in significant benefits towards reducing the matrix effects during LC-MS analysis. Therefore this work describes a simple method to enrich and clean up NSAIDs and clofibric acid from sewage water using molecularly imprinted solid-phase extraction (MISPE). Final analysis was performed by liquid chromatography-tandem mass spectrometry. The performance of this method has been evaluated in fortified tap and sewage water in terms of recovery, precision, linearity, and method quantification limit. Recovery for all compounds ranged in all matrices between 84 and 116% with intra-day R.S.D. values below 11.5%. Matrix effect evaluation demonstrated that even complex sample matrixes, such as pond or sewage water did not showed significant ion suppression/enhancement compared to tap water. The performance of the method was further emphasized by the study of pond water, which receives treated water from a sewage treatment plant in south Sweden. Raw sewage and treated water were also tested. In those samples, all acidic pharmaceuticals were detected in concentration above method quantification limits ranging from 5.1 to 5153.0 ng L⁻¹.     

Greedy Gaussian segmentation of multivariate time series

Advances in Data Analysis and Classification - We consider the problem of breaking a multivariate (vector) time series into segments over which the data is well explained as independent samples...     

Kinship systems and inverse semigroups

Inverse semigroups are introduced as a model for kinship structures. It is shown that semigroups are implied by the traditional anthropological law of uniform descent, and that inverses are suggested by the principle of reciprocity. A separation into a ‘surface’ and a ‘deep’ level of analysis was induced by viewing a kinship system as a partition on an underlying inverse semigroup. Some Omaha‐type kinship systems are decomposed into direct and semidirect products. Additional assumptions are made to deiive a theoretical similarity measure, which is then compared with a judged similarity task on Tenejapan Indians. The results of this preliminary experiment seem to be encouraging.