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The aim of this work was to study sulfamethoxazole (SMX) removal efficiency and fate of corresponding sul genes in a stacked microbial fuel cell-constructed wetland coupled biofilm electrode reactor system (MFC-CW-BER). Findings showed that two stacked MFC-CWs could provide a relatively stable electricity supply to support the biofilm for SMX removal. Excellent SMX removal (>99.29%) was obtained in the BER-MFC-CW. Compared with the 2000 mug L?1 SMX influent, the relative abundance of the sul genes in biofilm media and effluent was enhanced with continuously high concentrations of SMX (4000 mug L?1). The relative abundances of sul genes in biofilm media and effluent increased as the hydraulic retention time decreased. However, there was no obvious variation in the relative abundance of sul genes in the effluent from MFC-CWs. No effect could be observe of the direct voltage and bioelectricity on the relative abundance of the sul genes in the BER.

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The results of electronic structure studies aimed at determining accurate enthalpies of formation and proton affinities for a comprehensive set of C4H7N and C3H3ON compounds are reported. The calculated thermodynamic values are rationalized in terms of the nitrogen functionality and the influence of unsaturated C-C bonding environments. Using these results, it is proposed that a previously unidentified mass 70amu tropospheric ion is the protonated form of 1-pyrroline, an unsaturated nitrogen heterocyclic compound emitted into the atmosphere by both plant and animal biological activity.

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A novel strategy for the dehydrogenation of the NH?NH bond is disclosed using potassium tert-butoxide (tBuOK) in liquid ammonia (NH3) under air at room temperature. Its synthetic value is well demonstrated by the highly efficient synthesis of aromatic azo compounds (up to 100 % yield, 3 min), heterocyclic azo compounds, and dehydrazination of phenylhydrazine. The broad application of this strategy and its benefit to chemical biology is proved by a novel, convenient, one-pot synthesis of aliphatic diazirines, which are important photoreactive agents for photoaffinity labeling.

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The electrochemical abatement of the antibiotic sulfamethoxazole (SMX) from aqueous solutions at pH 3.0 has been carried out by anodic oxidation and electro-Fenton (EF) processes with H2O2 electrogeneration. The electrolyses have been performed using a small, undivided cell equipped with a Pt or thin film boron-doped diamond (BDD) anode and a carbon-felt cathode. The higher performance of the EF process with 0.2mM Fe2+ in a BDD/carbon felt cell is demonstrated. This is due to the higher production of OH radicals, as well as to the simultaneous degradation at the anode surface and in the bulk solution. At low current, the oxidation at the anode was predominant; at high current, SMX was pre-eminently degraded in the bulk. SMX was quickly destroyed under all the conditions tested, following pseudo first-order kinetics; however, the almost total removal of the total organic carbon was only achieved in the BDD/carbon felt cell. The reaction by-products were quantified by chromatographic techniques and thus, the reaction pathway for the mineralization of SMX by EF has been elucidated. Hydroxylation of SMX on the sulfanilic ring is suggested as the first step, followed by the formation of p-benzoquinone and 3-amino-5-methylisoxazole. Their oxidative cleavage led to the formation of five carboxylic acids that were finally mineralized to CO2; the release of NH4+, NO3-, and SO42- accounted for almost 100% of the initial nitrogen and sulfur content. The absolute rate constants for the oxidative degradation of SMX and the detected aromatic by-products have also been determined.

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The present invention relates to compounds of formula (I) useful as inhibitors of one or more histone demethylses, such as KDM5. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and the compounds for use in methods for the treatment of various disorders. Formula (I): or a salt thereof, wherein: A is selected from the group consisting of:

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A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M1 receptor subtype) and isolated guinea-pig atrium (M2 receptor subtype) and ileum (M3 receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.

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The kinetics of enolization and degradation of N-(5-methyl-4-isoxazolyl)- 4-amino-1,2-naphthoquinone (1) was investigated in aqueous solutions over a pH range of 7.30 to 12.25, at 35 C and at constant ionic strength (mu = 0.5) using reversed-phase HPLC. Pseudo-first-order kinetics was observed throughout the pH range studied. The rate of enolization (k(e)), the keto- enol equilibrium constant (K(t)), and specific base catalysis rate constant (k(OH)) were determined. Good agreement between the theoretical pH-rate profile and the experimental data supports the proposed transformation process. The average recovery for 1 and its tautomerization product 2- hydroxy-N-(5-methyl-4-isoxazolyl)-1,4-naphthoquinone 4-imine (2) from mixtures of different composition was evaluated.

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Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.

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The matrix metalloproteinase family has been a pharmaceutical target for most of the last three decades, but success has been hampered by unwanted side effects caused by lack of selectivity, poor oral bioavailability and decreased potency in vivo. The surface-expressed metalloproteinases ADAM10 and ADAM17, the latter also referred to as TACE, play important roles in various physiological processes, especially involving tissue repair and development. Because of its role in the release of the cytokine TNF-alpha TACE has been a key target for pharmaceutical intervention in the treatment of rheumatoid arthritis. An extensive body of structural activity data has been developed for a series of small molecule inhibitors of TACE based on a sulfonamide scaffold containing key acetylenic substituents. We have undertaken an extensive molecular modeling study of select members of this ligand group to better understand the structural nuances involved in the development of ever more potent TACE inhibitors, and identify those elements of structure-based design that would enhance the selectivity of such inhibitors for TACE over ADAM10. Results include the identification of a flexible loop, comparable to that found in other MMPs that plays a subtle, yet significant, role in determining inhibitor potency.

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Neurodegenerative disorders are emerging as leading contributors to the global disease burden. While some drug-based approaches have been designed to limit or prevent neuronal loss following acute damage or chronic neurodegeneration, regeneration of functional neurons in the adult Central Nervous System (CNS) still remains an unmet need. In this context, the exploitation of endogenous cell sources has recently gained an unprecedented attention, thanks to the demonstration that, in some CNS regions or under specific circumstances, glial cells can activate spontaneous neurogenesis or can be instructed to produce neurons in the adult mammalian CNS parenchyma. This field of research has greatly advanced in the last years and identified interesting molecular and cellular mechanisms guiding the neurogenic activation/conversion of glia. In this review, we summarize the evolution of the research devoted to understand how resident glia can be directed to produce neurons. We paid particular attention to pharmacologically-relevant approaches exploiting the modulation of niche-associated factors and the application of selected small molecules.

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