Acylation of sulfonamines using silica grafted 1-butyl-3-(3-triethoxysilylpropyl)-4,5-dihydroimidazolium ionic liquids as catalysts

Heterogeneous immobilized ionic liquid catalysts were prepared via grafting of 1,3-dimethyl-3-(3-triethoxysilylpropyl)-imidazolium tetrafluoroborate or bist{(trifluoromethyl)sulfonyl} imide ([NTf2](-)) on silica supports with different surfaces and pore size. In addition to the adsorption-desorption isotherms of nitrogen at -196C, the catalysts were characterized by TG-DTA, XPS, DRIFTS, DR-UV-vis, NMR, and XRD techniques. The catalytic behavior was checked in the acylation of three different sulfonamines: benzenesulfonamine, p-nitrobenzene-sulfonamine, and p-methoxybenzene-sulfonamine with acetic acid, acetic anhydride and maleic anhydride. These tests confirmed the acid Lewis properties of these catalysts. (c) 2007 Elsevier B.V. All rights reserved.

Kinetic analysis of the cleavage of human protease-activated receptor-1/2/3 and 4 using quenched-fluorescent peptide substrates

Protease-activated receptors [PARs] are a family of G-protein-coupled seven-transmembrane domain receptors that are activated by proteolytic cleavage of their amino-terminal exodomain. To characterize the cleavage rate of human PAR-1 / 2 / 3 and 4 by trypsin and thrombin, four synthetic quenched-fluorescent peptide substrates have been synthesized. Each substrate consisted of a ten-residue peptide spanning the receptor activation cleavage site and using progress-curve kinetics, k(cat)/K-m values were determined.

3-anilino-4-arylmaleimides: Potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)

Potent 3-anilino-4-arylmaleimide glycogen synthase kinase-3 (GSK-3) inhibitors have been prepared using automated array methodology. A number of these are highly selective, having little inhibitory potency against more than 20 other protein kinases. (C) 2001 Elsevier Science Ltd. All rights reserved.

Polymorphism in Sulfadimidine/4-Aminosalicylic Acid Cocrystals: Solid-State Characterization and Physicochemical Properties

Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid-state characterization of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high-resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared with a physical equimolar mixture and pure SD.

Preschool Children's Awareness of and Attitudes Toward Difference: A Study of 3- and 4-Year-Old Children in Northern Ireland

This paper presents the findings of a large-scale survey (n = 1,049) of the ethnic awareness and attitudes of 3-4 year old children in Northern Ireland. In drawing upon and applying Bourdieu’s notion of habitus, the paper demonstrates how even at this age, the children are already beginning to embody and internalize the cultural habits and dispositions of their respective ethnic groups. This was found in relation to the children’s: friendships choices; preferences for particular national flags; and dispositions towards specific sports associated with their respective communities. Informed by the work of Bourdieu, the paper concludes by arguing for the need for greater use of quantitative methods employing multivariate and multilevel statistical analyses and for these to be based on a more open and meaningful engagement with the findings of indepth qualitative and ethnographic research in this area.

Hapten synthesis and antibody production for the development of a melamine immunoassay

The incorporation of melamine into food products is banned but its misuse has been widely reported in both animal feeds and food. The development of a rapid screening immunoassay for monitoring of the substance is an urgent requirement. Two haptens of melamine were synthesized by introducing spacer arms of different lengths and structures on the triazine ring of the analyte molecular structure. 6-Aminocaproic acid and 3-mercaptopropionic acid were reacted with 2-chloro-4,6-diamino-1,3,5-triazine (CAAT) to produce hapten 1[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylamino) hexanoic acid] and hapten 2[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylthio) propanoic acid]. respectively. The molecular structures of the two haptens were identified by I H nuclear magnetic resonance spectrometry, mass spectrometry and infrared spectrometry. An immunogen was prepared by coupling hapten 1 to bovine serum albumin (BSA). Two plate coating antigens were prepared by coupling both haptens to egg ovalbumin (OVA). A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed to evaluate homogeneous and heterogeneous assay formats. The results showed that polyclonal antibodies with high titers were obtained, and the heterogeneous immunoassay format demonstrated a better performance with an IC50 of 70.6 ng mL(-1), a LOD of 2.6 ng mL(-1) and a LOQ of 7.6 ng mL(-1). Except for cyromazine, no obvious cross-reactivity to common compounds was found. The data showed that the hapten synthesis was successful and the resultant antisera could be used in an immunoassay for the rapid and sensitive detection of this banned chemical. (C) 2010 Elsevier B.V. All rights reserved.

Retention of toxic chromium from aqueous phase by H3PO4-activated lignin: Effect of salts and desorption studies

In this study, the feasibility of using H₃PO₄-activated lignin for hexavalent chromium adsorption has been investigated. The composite of activated lignin was characterized using FTIR, XRD and SEM with EDAX analysis. It was observed that the pH had a strong effect on the adsorption capacity; adsorption of Cr(VI) was more favorable at acidic pH with maximum uptake at pH 2. The adsorption equilibrium data were best represented by Koble-Corrigan isotherm. The monolayer sorption capacity obtained from the Langmuir model was found to be 77.85 mg/g. Adsorption showed pseudo-second order rate kinetics and the process involving the rate-controlling step is complex as it involves both film and intraparticle diffusion processes. The NaOH desorbing agent was able to release approximately 84% of metal ions. Thermodynamic parameters showed that the sorption process is exothermic and non-spontaneous. The overall Cr(VI) retention on the activated lignin surface perhaps includes both the physical adsorption of Cr(VI) and the consequent reduction of Cr(VI) to Cr(III). (C) 2011 Elsevier B.V. All rights reserved.

Steam reforming of ethanol over Co3O4–Fe2O3 mixed oxides

Co3O4, Fe2O3 and a mixture of the two oxides Co–Fe (molar ratio of Co3O4/Fe2O3 = 0.67 and atomic ratio of Co/Fe = 1) were prepared by the calcination of cobalt oxalate and/or iron oxalate salts at 500 °C for 2 h in static air using water as a solvent/dispersing agent. The catalysts were studied in the steam reforming of ethanol to investigate the effect of the partial substitution of Co3O4 with Fe2O3 on the catalytic behaviour. The reforming activity over Fe2O3, while initially high, underwent fast deactivation. In comparison, over the Co–Fe catalyst both the H2 yield and stability were higher than that found over the pure Co3O4 or Fe2O3 catalysts. DRIFTS-MS studies under the reaction feed highlighted that the Co–Fe catalyst had increased amounts of adsorbed OH/water; similar to Fe2O3. Increasing the amount of reactive species (water/OH species) adsorbed on the Co–Fe catalyst surface is proposed to facilitate the steam reforming reaction rather than decomposition reactions reducing by-product formation and providing a higher H2 yield.

Three-dimensional graphene-Co3O4 cathodes for rechargeable Li-O2 batteries

A three-dimensional (3D) graphene-Co₃O₄ electrode was prepared by a two-step method in which graphene was initially deposited on a Ni foam with Co₃O₄ then grown on the resulting graphene structure. Cross-linked Co₃O₄ nanosheets with an open pore structure were fully and vertically distributed throughout the graphene skeleton. The free-standing and binder-free monolithic electrode was used directly as a cathode in a Li-O₂ battery. This composite structure exhibited enhanced performance with a specific capacity of 2453 mA h g^-1 at 0.1 mA cm^-2 and 62 stable cycles with 583 mA h g^-1 (1000 mA h g_carbon^-1). The excellent electrochemical performance is associated with the unique architecture and superior catalytic activity of the 3D electrode. 

An array-based study of reactivity under solvent-free mechanochemical conditions-insights and trends

An array-based approach is put forward to obtain insight into reactivity under mechanochemical solvent-free conditions. We describe a survey of sixty potential reactions between twelve metal salts MX2 {(M = Cu, X-2 = (OAc)(2), (HCO2)(2), (F3CCO2)(2), (acac)(2), (F(6)acac)(2), (NO3)(2), SO4; M = Ni, X-2 = (OAc)(2), (NO3)(2), SO4; M = Zn, X-2 (OAc)(2), (NO3)(2)} and five bridging organic ligands {isonicotinic acid (HINA), 1,4-benzenedicarboxylic acid (H2BDC), acetylenedicarboxylic acid (H(2)ADC), 1,3,5-benzenetricarboxylic acid (H3BTC), 4,4'-bipyridyl (BIPY). Reaction conditions involved a ball mill, applied for 15 min at 30 Hz, without external heating. When examined by XRPD, forty of the combinations gave detectable reactions, thirty-eight with crystalline products. Of these, twenty-nine reactions were quantitative (consuming all of at least one reactant). Comparison of XRPD patterns with patterns simulated from single crystal X-ray diffraction data in the Cambridge Structural Database allowed structural identification of six products. Of particular interest are the microporous framework materials [Cu(INA)(2)] and [Cu-3(BTC)(2)] (HKUST-1) obtained by reaction of the corresponding carboxylic acids with copper acetate. Other non-porous polymers with 3-dimensional connectivity, [Ni(ADC)(H2O)(4)], or 1-dimensional connectivity, [Cu(acac)(2)(BIPY)] and [Cu(F6acac)(BIPY)] were also obtained. Reaction between zinc acetate and H2ADC gave a new product which had not previously been characterised by single-crystal X-ray crystallography, but whose XRPD pattern suggests that it is isostructural with the known nickel polymer [Ni(ADC)(H2O)(4)]. Two further isostructural nickel and zinc products were obtained in reactions between HINA and nickel nitrate and zinc nitrate. Trends observed within the array are discussed. Copper acetate and copper formate were the most effective starting materials for reaction with carboxylic acids, potentially related to the basicity of their anions and the solvating effects of the formic and acetic acid byproducts. Amongst the ligands there was a general negative corelation between melting point and reactivity. The issue of pore templating in microporous phases and the generation of new structures is also discussed in relation to the Cu(INA)(2), Cu-3(BTC)(2) and nickel nitrate-BIPY systems. Overall, the study suggests that mechanochemical reactivity between metal salts and organic ligands under solvent free conditions is remarkably general. Use of array-based approaches as demonstrated here is advocated a useful way to reveal underlying trends in reactivity under solvent free mechanochemical conditions and to highlight particular cases for more detailed study.

Crystal structure of pyridinium 1,1 '-bis(4-hydroxy-pyrimid-6-on-2-thion-5-yl)-1 ''-(4-nitrophenyl)methane methanol solvate monohydrate, (C5H6N)(C15H10N5O6S2)center dot CH3OH center dot H2O

C21H22N6O8S2, monoclinic, P12(1)/n1 (no. 14), a = 10.1931(8) angstrom, b = 11.9627(7) angstrom, c = 20.299(2) angstrom, beta = 95.131(4)degrees, V = 2465.2 A(3), Z = 4, R-gt(F) = 0.079, wR(ref)(F-2) = 0.229, T = 100 K.

Lanthanide(III) nitrobenzenesulfonates as new nitration catalysts: The role of the metal and of the counterion in the catalytic efficiency

Lanthanide(III) complexes of p-nitrobenzenesulfonic acid, Ln(p-NBSA)(3), m-nitrobenzenesulfonic acid, Ln(m-NBSA)(3), and 2,4-nitrobenzenesulfonic acid, Ln(2,4-NBSA)(3), were prepared, characterized and examined as catalyst for the nitration of benzene, toluene, xylenes, naphthalene, bromobenzene and chlorobenzene. The initial screening of the catalysts showed that lanthanum(III) complexes were more effective than the corresponding ytterbium(III) complexes, and that catalysts containing the bulky 2,4-NBSA ligand were less effective than the catalyst containing p-NBSA (nosylate) or m-NBSA ligands. Examination of a series of Ln(p-NBSA)(3) and Ln(m-NBSA)(3) catalysts revealed that there is a clear correlation between the ionic radii of the lanthanide(III) ions and the yields of nitration, with the lighter lanthanides being more effective. The X-ray single crystal structure of Yb(m-NBSA)(3).6H(2)O shows that two m-NBSA ligands are directly bound to the metal centre while the third ligand is not located in the first coordination sphere, but it is hydrogen bonded to one of the water molecules which is coordinated to ytterbium(III). NMR studies suggest that this structure is preserved under the conditions used in the nitration reaction. The structure of Yb(m-NBSA)(3) is markedly different from the structure of the well-known ytterbium(III) triflate catalyst. The coordination of the nitrobenzenesulfonate counterion to the lanthanide(III) ion suggests that steric effects might play an important role in determining the efficiency of these novel nitration catalysts. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

Partial agonism, neutral antagonism, and inverse agonism at the human wild-type and constitutively active cholecystokinin-2 receptors

Cholecystokinin receptor-2 (CCK2R) is a G protein receptor that regulates a number of physiological functions. Activation of CCK2R and/or expression of a constitutively active CCK2R variant may contribute to human diseases, including digestive cancers. Search for antagonists of the CCK2R has been an important challenge during the last few years, leading to discovery of a set of chemically distinct compounds. However, several early-discovered antagonists turned out to be partial agonists. In this context, we carried out pharmacological characterization of six CCK2R antagonists using COS-7 cells expressing the human CCK2R or a CCK2R mutant having a robust constitutive activity on inositol phosphates production, and we investigated the molecular mechanisms which, at a CCK2R binding site, account for these features. Results indicated that three compounds, 3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3- yl)-N'-(3-methylphenyl)urea (L365,260), 4-{[2-[[3-(lH-indol-3-yl)-2- methyl-1-oxo-2-[[[1.7.7-trimethyl-bicyclo[2.2.1]hept-2-yl)-oxy]carbonyl]amino] propyl]amino]-1-phenylethyl]amino-4-oxo-[lS-la.2[S*(S*)]4a]} -butanoate N-methyl-D-glucamine (PD135, 158), and (R)-1-naphthalenepropanoic acid, b-[2-[[2-(8-azaspiro-[4.5]dec-8-ylcarbonyl)-4,6-dimethylphenyl]amino]-2- oxoethyl] (CR2945), were partial agonists; one molecule, 1-[(R)-2,3-dihydro-1- (2,3-dihydro-1-(2-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl] -3-(3-methylphenyl)urea (YM022), was a neutral antagonist; and two compounds, N-(+)-[1-(adamant-1-ylmethyl)-2,4-dioxo-5-phenyl2,3,4,5-tetrahydro-1H-1, 5-benzodiazepin-3-yl]-N'-phenylurea (GV150,013X) and ([(N-[methoxy-3 phenyl] N-[N-methyl N-phenyl carbamoylmethyl], carbomoylmethyl)-3 ureido]-3-phenyl)2-propionic acid (RPR101,048), were inverse agonists. Furthermore, target- and pharmacophore-based docking of ligands followed by molecular dynamic simulation experiments resulted in consistent motion of aromatic residues belonging to a network presumably important for activation, thus providing the first structural explanations for the different pharmacological profiles of tested compounds. This study confirms that several referenced so-called antagonists are in fact partial agonists, and because of this undesired activity, we suggest that newly generated molecules should be preferred to efficiently block CCK2R-related physiological effects. Furthermore, data on the structural basis for the different pharmacological features of CCK2R ligands will serve to further clarify CCK2R mechanism of activation. Copyright © 2006 The American Society for Pharmacology and Experimental Therapeutics.