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The widespread occurrence of sulfonamides (SAs) in natural waters, wastewater, soil and sediment has raised increasing concerns about their potential risks to human health and ecological systems. Sulfate radical (SO4[rad]?)-based advanced oxidation processes (SR-AOPs) have become promising technologies to remove such contaminants in the environment. The present study systematically investigated the degradation of four selected SAs with different five-membered heterocyclic rings, namely, sulfamethoxazole (SMX), sulfisoxazole (SIX), sulfathiazole (STZ), and sulfamethizole (SMT), by thermo-activated persulfate (PS) process, and the role of heterocyclic rings was assessed particularly. The results revealed that all the selected SAs could be degraded efficiently by thermo-activated PS process and their decay rates were appreciably increased with increasing temperature. For instance, degradation rates of STZ increased from 0.3 × 10?3 to 19.5 × 10?3 min?1 as the temperature was increased from 30 to 60 C. Under the same experimental conditions, the degradation rates of SAs followed the order of SIX > SMX ? STZ > SMT, which was in accordance with decay rates of their R-NH2 moieties. Kinetic results indicated that five-membered heterocyclic rings could serve as reactive moieties toward SO4[rad]? attack, which were confirmed by frontier electron density (FED) calculations. Based on the transformation products identified by high-resolution mass spectrometry (HR-MS), five different oxidation pathways, including hydroxylation, aniline moiety oxidation, dimerization, sulfonamide bond cleavage, and heterocyclic ring oxidation/cleavage were proposed. Moreover, the degradation efficiency in real surface water (RSW) was found to be slightly slower than that in artificial surface water (ASW), suggesting that SR-AOPs could be an efficient approach for remediation of soil and water contaminated by these SAs.

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A straightforward procedure using density functional theory (M06 2X) coupled with a group-equivalent approach is described that was used to calculate gas-phase heat of formation (DeltafHg,298) values for buckminsterfullerene (C60), C70 fullerene (C70), corannulene, coronene, and sumanene. This procedure was also used to calculate exceptionally accurate DeltafHg,298 values for a variety of single-ring aromatic and 2-7 ring polycyclic aromatic hydrocarbons (PAHs) as well as a large selection of other hydrocarbons and phenols. The approach described herein is internally consistent, and results for C60, C70, corannulene, coronene, and sumanene are in very close agreement with results reported by others who used higher-level computational theory. Statistical analysis of a test set containing benzene and 18 two to seven ring PAHs demonstrated that by using this approach a mean absolute deviation (MAD) and a root-mean-square deviation (RMSD) of 0.8 and 1.3 kJ/mol, respectively, were achieved for reference/experimental DeltafHg,298 values versus calculated/predicted DeltafHg,298 values. For statistical analysis of a larger test set containing 235 aromatic and aliphatic hydrocarbons and phenols, a MAD and a RMSD of 1.2 and 1.9 kJ/mol, respectively, were achieved for reference/experimental DeltafHg,298 values versus calculated/predicted DeltafHg,298 values.

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A unique synthetic approach to 3-hydroxy-4-substituted picolinonitriles is achieved via gold(I)-catalyzed cyclization of 4-propargylaminoisoxazoles and subsequent N-O bond cleavage of isoxazolopyridines under mild reaction conditions in a stepwise and one-pot fashion.

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Alkyl (Z)-2-[(E)-2-cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethyl-aminopropenoates (2) and (3) were transformed with C-and N-nucleophiles into alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-heteroarylpropenoates (10-13), 2H,5H-benzo-[b]pyran-2,5-diones (14) and (15), 2H,5H-pyrano[4,3-b]pyran-2,5-dione (16), 2H,5H-pyrano[3,2-c]benzo[b]pyran-2,5-dione (17), alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-arylamino- (28-40), and 3-heteroarylaminopropenoates (41-43), pyrido[1,2-a]pyrimidin-4-ones (50-53), thiazolo[3,2-a]pyrimidin-4-one (54), benzothiazolo[3,2-a]pyrimidin-4-one (55), and 1-heteroaryl-1H-imidazole-4-carboxylate (56). Compounds (28-43) exist in (2E, 2?E) form or as a mixture of (2E, 2?E) as a major and (2Z,2?E) form as a minor isomer.

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Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan’s poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130.

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Ring expansion of secondary methylenecyclopropyl amides in the presence of MgI2 was investigated. Various isomeric five-membered unsaturated lactams were obtained, depending on the character of the substituent Q. The amide group served as a nucleophile in ring closing as well as an activator for ring opening. In the presence of a variety of aryl aldimines or aldehydes, alkylative ring expansion occurred in a single step under mild and neutral conditions leading to gamma?-amino- or -hydroxy-alkylated pyrrol-2-ones. Also, it was shown that a 4-methylpyrrol-2-one could be transformed to a gamma-hydroxy-alkylated product by the use of a direct vinylogous aldol reaction. Copyright

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Here we present a two-step diastereoselective methodology building on a multicomponent aza-Diels-Alder reaction. Using previously unexplored cyclic ketones, heterocyclic amines and cyclopentadiene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between “drug-like” molecules and natural products.

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Compounds of formula (I); which are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VR1).

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Current application of human induced pluripotent stem cells (hiPSCs) technology in patient-specific models of neurodegenerative disorders recapitulate some of key phenotypes of diseases, representing disease-specific cellular modeling and providing a unique platform for therapeutics development. We review recent efforts toward advancing hiPSCs-derived neuronal cell types and highlight their potential use for the development of more complex in vitro models of neurodegenerative diseases by focusing on Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Amyotrophic lateral sclerosis. We present evidence from previous works on the important phenotypic changes of various neuronal types in these neurological diseases. We also summarize efforts on conducting low- and high-throughput screening experiments with hiPSCs toward developing potential therapeutics for treatment of neurodegenerative diseases. Lastly, we discuss the limitations of hiPSCs culture system in studying neurodegenerative diseases and alternative strategies to overcome these hurdles.

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Hydrogen bonding equilibrium constants have been measured for a large and varied selection of proton donors against a common acceptor (N-methylpyrrolidinone) and of proton acceptors against a common donor (4-nitrophenol).Together these have been used to create the log Kalpha and log Kbeta scales of proton donor and acceptor ability which are explicitly targeted to the needs of the medicinal chemist in the context of potential drug-receptor interactions.To this end they have been measured in 1,1,1-trichloroethane, a solvent never before used for hydrogen bonding studies but whose high dipolarity is considered a much better model for real biological membranes than the very non-polar solvents that have previously been employed.It is shown that this solvent imposes significant ranking changes on the solutes, since the charge transfer element in hydrogen bonding is reinforced at the expense of the purely electrostatic component.Nevertheless it is possible to scale previous data in such a way that over 80 functional group log Kalpha and log Kbeta values become available to the medicinal chemist (Table 4).In addition, data are given for a large number of parent heterocycles, most of which have never before been studied.We note that heterocycles are uniquely able to ‘fine-tune’ these scales, so providing at least one justification for their special interest to the medicinal chemist.In addition to equilibrium constants we have measured the spectroscopic quantities DeltanuC=O (for donors) and betasm (for acceptors).On various lines of evidence we suggest that these are enthalpy-related quantities and, following previous arguments, may function as alternative parameters suitable for use by the medicinal chemist under conditions of severe steric constraint.Cross-comparisons of these data allow conclusions to be drawn which consider ably illuminate the factors that influence hydrogen bond strength, and some of which have no precedent.A selection follows.Where a level comparison can be made, the donor order is OH>NH>CH and the acceptor order is N>O>S.However, within each category there are various sorts of family relationship.For example, phenols and alkanols lie on separate lines of log Kalpha vs. pKa, and a similar separation for log Kbeta is shown by 5- and 6-membered ring heterocycles.By contrast, OH and NH donors show a single relation between log Kalpha and DeltanuC=O, negative deviations from which are satisfactorily accounted for in terms of steric and stereoelectronic factors.The most important of the latter is lone-pair repulsion: ‘alpha-effect’ heterocycles are anomalously strong acceptors, whereas certain classes of donor, notably sulphonamides and carboxylic acids, are much weaker than would be expected from their pKa values.More subtle anomalies attach, inter alia, to heterocycles as donors, CH donors generally, and amines and sulphonamides as acceptors; all however can be rationalised.The extremes of both scales are charted.Alkyl thiols and amines are negligible as proton donors; correspondingly, ?-donor…

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