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Mechanistic Study (mechanistic + study)
Selected AbstractsInhibition of Diamino Pelargonic Acid Aminotransferase, an Enzyme of the Biotin Biosynthetic Pathway, by Amiclenomycin: A Mechanistic StudyHELVETICA CHIMICA ACTA, Issue 11 2003Stéphane Mann The mechanism of action of amiclenomycin (1a), a naturally occuring inhibitor of diaminopelargonic acid aminotransferase, has been established. The enzyme catalyzes the formation of an aromatic adduct between the inhibitor and pyridoxal-5,-phosphate. The structure of the adduct, determined by mass spectrometry, is in agreement with the reported X-ray crystal structure. Kinetic parameters, characteristic of kcat inhibitors, have been observed, with a KI value of 2,,M and a kinact value of 0.4,min,1. The irreversibility of the inactivation observed, in spite of the absence of covalent bond between the inhibitor and the protein, reveals the high affinity of the adduct for the active site. Two other cis -1-amino-4-substituted-cyclohexa-2,5-dienes, 3a and 4a, were also found to efficiently inhibit the enzyme. The trans -isomers were either much less potent (1b) or inactive (3b and 4b). The aminocyclohexadiene moiety, which is, apparently, responsible for the inhibition, could constitute an original pharmacophore for the design of new herbicides. [source] Layered Double Hydroxide Supported Nanoplatinum and Nanopalladium Catalyzed Allylation of Aldehydes: A Mechanistic StudyADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 15 2005M. Choudary Abstract Layered double hydroxide (LDH)-supported nanoplatinum(0) and nanopalladium(0) catalysts were prepared by a simple ion exchange technique and subsequent reduction with hydrazine hydrate and used for the allylation of aldehydes to give moderate to good yields of homoallylic alcohols. Detailed mechanistic studies of LDH-Pd(0)-catalyzed allylation using XPS and TGA-MS reveal that a monoallyl-palladium complex is the key intermediate for the catalytic cycle. [source] A Mechanistic Study on Alcohol Oxidations with Oxygen Catalysed by TPAP-Doped Ormosils in Supercritical Carbon DioxideADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2005Sandro Campestrini Abstract The heterogeneous oxidation of various alcohols with oxygen catalysed by TPAP-doped ormosils in scCO2 at 75,°C and 22.0,MPa has been studied in detail. Sol-gel segregation of TPAP into the inner porosity of an organically modified silica (ormosil) xerogel along with the use of a reaction medium which does not dissolve the catalyst, prevents aggregation of oxidation-inactive ruthenium derivatives without the need of chemical tethering. Thus, at least 140 TONs may be obtained in the oxidation of primary alcohols with the formation of aldehydes as sole reaction products. Investigation of the oxidation mechanism shows that the catalytic process exhibits a first-order dependence on the amount of catalyst, a fractional order on the alcohol concentration and a negative order for oxygen pressures higher than 0.2,bar. Evidence is presented for an associative oxidation mechanism simultaneously involving TPAP, organic substrate and oxygen. [source] Mechanistic Study of Partial Oxidation of Methane to Syngas Using In Situ Time-Resolved FTIR and Microprobe Raman SpectroscopiesTHE CHEMICAL RECORD, Issue 2 2002Mechanism of Methane Partial Oxidation Abstract In situ time-resolved Fourier transform infrared (FTIR) and microprobe Raman spectroscopies were used to characterize the reaction mechanisms of the partial oxidation of methane to syngas over SiO2 - and ,-Al2O3 -supported rhodium and ruthenium catalysts. The interaction of both pure methane and a methane/oxygen mixture at a stoichiometric feed ratio with an oxygen-rich catalyst surface led to the formation of CO2 and H2O as the primary products. For the H2 -pretreated samples, the reaction mechanisms with the catalysts differ. Only Rh/SiO2 is capable of catalyzing the direct oxidation of methane to syngas, while syngas formation over Rh/g-Al2O3, Ru/SiO2, and Ru/g-Al2O3 can be achieved mainly via a combustion-reforming scheme. The significant difference in the mechanisms for partial oxidation of methane to syngas over the catalysts can be correlated to the differences in the concentration of oxygen species (O2,) on the catalyst surface during the reaction, mainly due to the difference in the nature of the metals and supports. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 2:102,112, 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10016 [source] ChemInform Abstract: Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation of Benzylic Amines to Imines and N-Substituted 1,2,3,4-Tetrahydroisoquinolines to Amides: Synthetic Applications and Mechanistic Study.CHEMINFORM, Issue 6 2010Man-Ho So Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Sonochemical Synthesis and Mechanistic Study of Copper Selenides Cu2-xSe, ,-CuSe, and Cu3Se2.CHEMINFORM, Issue 14 2002Yi Xie Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] The Role of Fluorine in the Stereoselective Tandem Aza-Michael Addition to Acrylamide Acceptors: An Experimental and Theoretical Mechanistic StudyCHEMISTRY - A EUROPEAN JOURNAL, Issue 30 2007Santos Fustero Prof. Abstract Aza-Michael additions of ,-amino esters to fluorinated acceptors take place in a highly stereoselective manner, to give partially modified ,[NHCH2]retropeptides incorporating a hydrolytically stable trifluoroalanine mimic. The reaction mechanism has been investigated experimentally and theoretically, in order to explain the effect of the trifluoromethyl group on the reactivity and the origins of the experimentally observed stereocontrol. The reaction is a two-step process, involving a tandem aza-Michael addition followed by a stereoselective hydrogen transfer. Both steps are base-catalyzed. The high level of stereocontrol is the result of a combination of electrostatic interactions and steric effects. Las adiciones aza-Michael de ,-amino ésteres a aceptores fluorados tienen lugar de un modo altamente estereoselectivo, para dar lugar a ,[NHCH2]retropéptidos parcialmente modificados que incorporan un mimético de trifluoroalanina, estable frente a la hidrólisis. El mecanismo de la reacción ha sido investigado experimental y teóricamente, a fin de explicar el efecto del grupo trifluorometilo en la reactividad y en los orígenes de estereocontrol observado experimentalmente. La reacción es un proceso en dos pasos, que implican una adición aza-Michael seguida de una transferencia estereoselectiva de hidrógeno. Ambos pasos están catalizados por una base. El origen del alto grado de estereocontrol radica en una combinación de interacciones electrostáticas y efectos estéricos. [source] The DMAP-Catalyzed Acetylation of Alcohols,A Mechanistic Study (DMAP=4-(Dimethylamino)pyridine)CHEMISTRY - A EUROPEAN JOURNAL, Issue 16 2005Shangjie Xu Dr. Abstract The acetylation of tert -butanol with acetic anhydride catalyzed by 4-(dimethylamino)pyridine (DMAP) has been studied at the Becke3,LYP/6-311+G(d,p)//Becke3,LYP/6-31G(d) level of theory. Solvent effects have been estimated through single-point calculations with the PCM/UAHF solvation model. The energetically most favorable pathway proceeds through nucleophilic attack of DMAP at the anhydride carbonyl group and subsequent formation of the corresponding acetylpyridinium/acetate ion pair. Reaction of this ion pair with the alcohol substrate yields the final product, tert -butylacetate. The competing base-catalyzed reaction pathway can either proceed in a concerted or in a stepwise manner. In both cases the reaction barrier far exceeds that of the nucleophilic catalysis mechanism. The reaction mechanism has also been studied experimentally in dichloromethane through analysis of the reaction kinetics for the acetylation of cyclohexanol with acetic anhydride, in the presence of DMAP as catalyst and triethylamine as the auxiliary base. The reaction is found to be first-order with respect to acetic anhydride, cyclohexanol, and DMAP, and zero-order with respect to triethyl amine. Both the theoretical as well as the experimental studies strongly support the nucleophilic catalysis pathway. [source] Graphite-Supported Gold Nanoparticles as Efficient Catalyst for Aerobic Oxidation of Benzylic Amines to Imines and N -Substituted 1,2,3,4-Tetrahydroisoquinolines to Amides: Synthetic Applications and Mechanistic StudyCHEMISTRY - AN ASIAN JOURNAL, Issue 10 2009Man-Ho So Abstract Selective oxidation of amines using oxygen as terminal oxidant is an important area in green chemistry. In this work, we describe the use of graphite-supported gold nanoparticles (AuNPs/C) to catalyze aerobic oxidation of cyclic and acyclic benzylic amines to the corresponding imines with moderate-to-excellent substrate conversions (43,100,%) and product yields (66,99,%) (19,examples). Oxidation of N -substituted 1,2,3,4-tetrahydroisoquinolines in the presence of aqueous NaHCO3 solution gave the corresponding amides in good yields (83,93,%) with high selectivity (up to amide/enamide=93:4) (6,examples). The same protocol can be applied to the synthesis of benzimidazoles from the reaction of o -phenylenediamines with benzaldehydes under aerobic conditions (8,examples). By simple centrifugation, AuNPs/C can be recovered and reused for ten consecutive runs for the oxidation of dibenzylamine to N -benzylidene(phenyl)methanamine without significant loss of catalytic activity and selectivity. This protocol "AuNPs/C+O2" can be scaled to the gram scale, and 8.9,g (84,% isolated yield) of 3,4-dihydroisoquinoline can be obtained from the oxidation of 10,g 1,2,3,4-tetrahydroisoquinoline in a one-pot reaction. Based on the results of kinetic studies, radical traps experiment, and Hammett plot, a mechanism involving the hydrogen-transfer reaction from amine to metal and oxidation of M-H is proposed. [source] Mechanistic Study of the Reaction of Thiol-Containing Enzymes with ,,,-Unsaturated Carbonyl Substrates by Computation and ChemoassaysCHEMMEDCHEM, Issue 6 2010Alexander Paasche Abstract We investigated the reactions between substituted ,,,-unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS-CoV Mpro) by etacrynic acid derivatives as well as for the excess toxicity of substituted ,,,-unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4-addition followed by a ketonization step, and underscores the importance of a base-catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron-pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s - cis conformation leads to higher reactivity than the s - trans conformation. The computed data explain the trends in measured inhibition potencies of substituted ,,,-unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease. [source] Mechanistic study of saikosaponin-d (Ssd) on suppression of murine T lymphocyte activationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Vincent Kam Wai Wong Abstract Saikosaponin-d (Ssd) is a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae). Previous findings showed that Ssd exhibits a variety of pharmacological and immunomodulatory activities including anti-inflammatory, anti-bacterial, anti-viral and anti-cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF-,B, NF-AT and AP-1 signaling pathways, cytokine secretion, and IL-2 receptor expression. The results demonstrated that Ssd not only suppressed OKT3/CD28-costimulated human T cell proliferation, it also inhibited PMA, PMA/Ionomycin and Con A-induced mouse T cell activation in vitro. The inhibitory effect of Ssd on PMA-induced T cell activation was associated with down-regulation of NF-,B signaling through suppression of IKK and Akt activities. In addition, Ssd suppressed both DNA binding activity and the nuclear translocation of NF-AT and activator protein 1 (AP-1) of the PMA/Ionomycin-stimulated T cells. The cell surface markers like IL-2 receptor (CD25) were also down-regulated together with decreased production of pro-inflammatory cytokines of IL-6, TNF-, and IFN-,. These results indicate that the NF-,B, NF-AT and AP-1 (c-Fos) signaling pathways are involved in the T cell inhibition evoked by Ssd, so it can be a potential candidate for further study in treating T cell-mediated autoimmune conditions. J. Cell. Biochem. 107: 303,315, 2009. © 2009 Wiley-Liss, Inc. [source] Mechanistic study of electroosmotic transport across hydrated nail plates: Effects of pH and ionic strengthJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2008Jinsong Hao Abstract The objective of this study was to investigate the effects of pH and ionic strength on electroosmotic transport in transungual iontophoresis. Transungual iontophoretic transport of model neutral permeants mannitol (MA) and urea (UR) across fully hydrated human nail plates in phosphate-buffered saline of different pH and ionic strengths were investigated in vitro. Two protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport at 0.1 and/or 0.3 mA. Nail plate electrical resistance and water uptake of nail clippings were measured at various pH and ionic strengths. In the pH study, electroosmosis enhanced the anodal transport of MA at pH 9 and cathodal transport at pH 3. The Peclet numbers of MA were more than two times higher than those of UR under these conditions. No significant electroosmosis enhancement was observed for MA and UR at pH 5. In the ionic strength study, a decrease in solution ionic strength from 0.7 to 0.04 M enhanced electroosmotic transport. Nail electrical resistance increased with decreasing the ionic strength of the equilibrating solution, but reached a plateau when the ionic strength was less than approximately 0.07 M. Solution pH and ionic strength had no significant effect on nail hydration. Under the studied pH and ionic strength conditions, the effects of electroosmosis were small compared to the direct-field effects in transungual iontophoretic transport of small to moderate size permeants. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5186,5197, 2008 [source] Mechanistic study of membrane concentration and recovery of Listeria monocytogenesBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2005Wan-Tzu Chen Abstract Detection of the foodborne pathogen Listeria monocytogenes requires that food samples be processed to remove proteins and lipids, concentrate microorganisms to a detectable concentration, and recover the concentrated cells in a small volume compatible with micron-scale biochips. Mechanistic considerations addressed in this research include the roles of membrane structure, pore size, and detergents in maximizing recovery of cells from a complex biological fluid. The fluid in this case was a food sample (hotdog extract) inoculated with L. monocytogenes. This study showed how membrane filtration using a syringe filter is able to concentrate L. monocytogenes by 95× with up to 95% recovery of living microorganisms by concentrating 50 mL of food sample into a volume of 500 ,L. Tween 20 was added to the sample to prevent irreversible adsorption of the microorganism to the membrane and thereby help to ensure high recovery. Comparison of polycarbonate, mixed cellulose, nylon, and PVDF membranes with 0.2 to 0.45 ,m pores showed the 0.2 ,m polycarbonate membrane with straight through, mono-radial pores gives the highest recovery of living microorganisms. The mixed cellulose, nylon, and PVDF membranes have a fibrous structure whose characteristic openings are much larger than their effective pore size cut-offs of 0.22 or 0.45 ,m. We define conditions for rapid membrane-based cell concentration and recovery that has the potential to supplant enrichment steps that require a day or more. This approach has the added benefit of facilitating examination of a large amount of fluid volume by reducing its volume to a range that is compatible with the microliter scales of biochip or other biosensor detection systems. © 2004 Wiley Periodicals, Inc. [source] Synthesis, Characterization, and Protonation Reactions of Ar-BIAN and Ar-BICAT Diimine Platinum Diphenyl ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 9 2010Jerome Parmene Abstract PtII diphenyl complexes (N,N)PtPh2 [N,N = diimines Ar,N=C(An)C=N,Ar with Ar = substituted aryl groups] have been prepared and characterized by 1H, 13C, and 195Pt NMR spectroscopy. The 195Pt NMR spectroscopic data establish the electronic influence exerted by substituents at the backbone of the diimine ligand system to the metal center. When compared to diimines Ar,N=CMe,CMe=N,Ar, the electron-withdrawing ability of the Ar-BIAN ligand and the electron-donating ability of the O,O-heterocyclic Ar-BICAT systems are demonstrated. Trends in 195Pt NMR chemical shifts suggest that electronic tuning of the metal center is better achieved through variations of the diimine backbone substituents rather than variation of the substituents at the N-Aryl groups. Protonation of (N,N)PtPh2 in dichloromethane/acetonitrile at ,78 °C furnishes the corresponding PtIV hydrides (N,N)PtPh2H(NCMe)+. The PtIV hydrides liberate benzene with the formation of (N,N)PtPh(NCMe)+ when the temperature is raised. A second protonation and rapid benzene elimination produces the dicationic PtII species (N,N)Pt(NCMe)22+ at approximately 50 °C. Protonation of (N,N)PtPh2 in the absence of acetonitrile results in the clean formation of (N,N)PtPh(,2 -C6H6)+ at temperatures that depend on the steric hindrance provided by the alkyl substituents at the diimine N-aryl groups. These findings support the notion that the metal is the kinetically preferred site of protonation. The results qualitatively agree with a recent mechanistic study of protonation-induced reactions of (diimine)PtPh2 complexes that bear simple methyl substituents at the diimine backbone. Several compounds have been crystallographically characterized. All complexes have the expected square planar environment at the metal. Modest variations in the metric parameters suggest that the Ar-BICAT system has a weaker trans influence than the Ar-BIAN and Ar-DAB systems. [source] Asymmetric Synthesis of (S)-Mirtazapine: Unexpected Racemization through an Aromatic ipso -Attack MechanismEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2008Marco van der Linden Abstract An asymmetric synthesis of (S)-mirtazapine has been achieved from the synthesis of the racemate by using (S)-1-methyl-3-phenylpiperazine as the starting material. Unfortunately, significant racemization was encountered in the final step, which involved an electrophilic aromatic ring closure of a alcohol by concentrated sulfuric acid. A significantly higher ee was observed when polyphosphoric acid (PPA) was used instead. A remarkable correlation between the amount of PPA used and the ee of the product was revealed, namely, an increase in the ee upon decreasing the amount of PPA. This trend was paralleled by the formation of an increasing amount of a side-product upon lowering the amount of PPA. The racemization and formation of a side-product can be explained by an ipso -attack mechanism during the electrophilic aromatic ring-closure reaction. This mechanism was supported by a mechanistic study using a deuterium-labeled substrate.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Unusual products in reactions using ethyldimesitylborane, mesityllithium, and carbonyl compoundsHETEROATOM CHEMISTRY, Issue 5 2001Takayuki Kawashima Unusual carbonyl adducts, Mes2BCH=CHCHCH3CRR1OH, were obtained by sequential treatment of ethyldimesitylborane with mesityllithium (<1.0 equiv.) and carbonyl compounds instead of the normal adducts, Mes2BCHCH3CRR1OH. A mechanistic study was carried out. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:354,357, 2001 [source] Prostaglandin E2 promotes cell proliferation via protein kinase C/extracellular signal regulated kinase pathway-dependent induction of c-Myc expression in human esophageal squamous cell carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 11 2009Le Yu Abstract Overexpression of cyclooxygenase-2 (COX-2) and elevation of its derivative prostaglandin E2 (PGE2) are implicated in human esophageal squamous cell carcinoma. The expression of c-Myc, an oncogenic transcription factor, is also upregulated in this malignant disease. This study sought to elucidate whether a functional connection exists between COX-2/PGE2 and c-Myc in esophageal squamous cell carcinoma. Results showed that PGE2 substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells. In this regard, PGE2 substantially increased the mRNA and protein expression of c-Myc and its association with the binding partner Max. Knockdown of c-Myc by RNA interference also significantly attenuated PGE2 -induced cell proliferation. Further, mechanistic study revealed that PGE2 increased the protein stability and nuclear accumulation of c-Myc via phosphorylation on serine 62 in an extracellular signal regulated kinase (ERK)-dependent manner. To this end, ERK activation by PGE2 was completely abolished by protein kinase C (PKC) inhibitors. Moreover, the effect of PGE2 on c-Myc expression was mimicked by EP2 receptor agonist. In addition, knockdown of EP2 receptor by EP2 siRNA attenuated PGE2 -induced c-Myc expression. Collectively, our findings suggest that PGE2 upregulates c-Myc via the EP2/PKC/ERK pathway. This study sheds new light on the carcinogenic mechanism of PGE2 in esophageal squamous cell carcinoma. © 2009 UICC [source] Kinetic and mechanistic study on the thermal reactivity of stabilized phosphorus ylides, part 3: [(Acetyl)(arylcarbamoyl)methylene]triphenylphosphoranes and [(alkoxycarbonyl)(arylcarbamoyl)methylene]triphenylphosphoranes and their thiocarbamoyl analoguesINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 1 2007R. Alan Aitken A series of five [(acetyl)(arylcarbabmoyl)methylene]triphenyl-phosphoranes 1a,e and their thiocarbamoyl analogues 2a,e, [(alkoxycarbonyl)(arylcarbamoyl)methylene]triphenylphosphoranes 3a,e and their thiocarbamoyl analogues 4a,e were prepared and fully characterized. All ylides are found under conditions of flash vacuum pyrolysis to fragment giving arylisocyanate or isothiocyanate and acetyl ylides or alkoxy ylides which undergo thermal extrusion of Ph3PO. A kinetic study shows that these reactions are unimolecular and are of first-order nature with no significant substituent effect. The thiocarbamoyl ylides 2 react from 4.6 to 42 times faster than their carbamoyl ylides 1, while the thiocarbamoyl ylides 4 react from 6.6 to 20.9 times faster than their carbamoyl ylides 3. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 6,16, 2007 [source] Kinetic and mechanistic study of the reaction of O(1D) with CF2HBrINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2001R. S. Strekowski A laser flash photolysis,resonance fluorescence technique has been employed to investigate the kinetics and mechanism of the reaction of electronically excited oxygen atoms, O(1D), with CF2HBr. Absolute rate coefficients (k1) for the deactivation of O(1D) by CF2HBr have been measured as a function of temperature over the range 211,425 K. The results are well described by the Arrhenius expression k1(T) = 1.72 × 10,10 exp(+72/T) cm3molecule,1 s,1; the accuracy of each reported rate coefficient is estimated to be ±15% (2,). The branching ratio for nonreactive quenching of O(1D) to the ground state, O(3P), is found to be 0.39 ± 0.06 independent of temperature, while the branching ratio for production of hydrogen atoms at 298 K is found to be 0.02,0.02+0.01. The above results are considered in conjunction with other published information to examine reactivity trends in O(1D) + CF2XY reactions (X,Y = H, F, Cl, Br). © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 262,270, 2001 [source] Highly Efficient and Stereoselective Julia,Kocienski Protocol for the Synthesis of ,-Fluoro-,,,-unsaturated Esters and Weinreb Amides Employing 3,5-Bis(trifluoromethyl)phenyl (BTFP) SulfonesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2008Diego Abstract ,-Fluoroacetates 3 and Weinreb amide 4, bearing a ,-[3,5-bis(trifluoromethyl)phenyl]sulfonyl (BTFP-sulfonyl) group at the ,-position, are employed in the highly stereoselective synthesis of ,-fluoro-,,,-unsaturated alkenoates and Weinreb amides, respectively. Aromatic and aliphatic aldehydes are condensed under extremely mild and simple reaction conditions using potassium carbonate in dimethylformamide at room temperature under solid-liquid phase-transfer catalysis conditions in good yields and high Z -diastereoselectivities, specially in the case of the fluorinated Weinreb amides. A detailed computational mechanistic study suggests a final non-concerted elimination of sulfur dioxide and 3,5-bis(trifluoromethyl)phenoxide and explains the observed high stereoselectivities for the reaction on the basis of thermodynamic and kinetic considerations. [source] Sulforaphane and its analogues inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyreneJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2009Katarzyna Skupinska Abstract CYP1A1 and CYP1A2 enzymes metabolize polycyclic aromatic hydrocarbons (PAHs) to the reactive oxyderivatives. PAHs can induce the activity of both enzymes, which increases its conversion and enhances risk of carcinogenesis. Thus, the inhibition of CYP enzymes is recognized as a cancer chemoprevention strategy. A well-known group of chemopreventive agents is isothiocyanates, which occur naturally in Brassica vegetables. In this paper, a naturally occurring sulforaphane and its two synthetic analogues isothiocyanate-2-oxohexyl and alyssin were investigated. The aim of the study was to determine whether the differences in the isothiocyanate structure change its ability to inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyrene in HepG2 and Mcf7 cells. Also a mechanistic study was performed including isothiocyanates' influence on CYP1A1 and CYP1A2 catalytic activity, enzymatic protein level, and AhR translocation. It was shown that both enzymes were significantly induced by benzo[a]pyrene, and isothiocyanates were capable of decreasing the induced activity. The inhibitory properties depend on the types of isothiocyanate and enzyme. In general, CYP1A2 was altered in the more meaningful way than CYP1A1 by isothiocyanates. Sulforaphane exhibited weak inhibitory properties, whereas both analogues were capable of inhibiting BaP-induced activity with the similar efficacy. The mechanistic study revealed that analogues decreased the CYP1A2 activity via the protein-level reduction and CYP1A1 directly. The results indicate that isothiocyanates can be considered as potent chemopreventive substances and the change in the sulforaphane structure increases its chemopreventive potency. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:18,28, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20259 [source] Ester prodrugs of morphine improve transdermal drug delivery: a mechanistic studyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2007Jhi-Joung Wang Two alkyl esters of morphine, morphine propionate (MPR) and morphine enanthate (MEN), were synthesized as potential prodrugs for transdermal delivery. The ester prodrugs could enhance transdermal morphine delivery. The mechanisms of this enhancing effect were elucidated in this study. Both prodrugs were more lipophilic than their parent drug as evaluated by the skin/vehicle partition coefficient (log P) and capacity factor (log K,). The in-vitro skin permeation of morphine and its prodrugs from pH 6 buffer was in the order of MEN > MPR > morphine. MPR and MEN respectively enhanced the transdermal delivery of morphine by 2- and 5-fold. A contrary result was observed when using sesame oil as the vehicle. The prodrugs were stable against chemical hydrolysis in an aqueous solution, but were readily hydrolysed to the parent drug when exposed to skin homogenate and esterase. Approximately 98% MPR and ,75% MEN were converted to morphine in an in-vitro permeation experiment. The viable epidermis/dermis contributed to a significant resistance to the permeation of ester prodrugs. According to the data of skin permeation across ethanol-, ,-terpineol-, and oleic acid-pretreated skin, MEN was predominantly transported via lipid bilayer lamellae in the stratum corneum. The intercellular pathway was not important for either morphine or MPR permeation. [source] Dominant Negative p63 Isoform Expression in Head and Neck Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 12 2004Joseph C. Sniezek MD Abstract Objectives/Hypothesis: p63, a member of the p53 family of genes, is vital for normal epithelial development and may play a critical role in epithelial tumor formation. Although p63 has been identified in various head and neck malignancies, a detailed analysis of which of the six isoforms of the p63 gene is present in normal mucosa and head and neck malignancies has not yet been performed. The study analyzed p63 isoform expression on the RNA and protein level in normal, diseased, and malignant mucosa of the head and neck to examine the differential expression of p63 isoforms in head and neck tumors versus adjacent nonmalignant tissue and to identify the predominant p63 isoform expressed in head and neck squamous cell carcinoma (HNSCC). Study Design: Three experiments were performed. In experiment 1, p63 expression was analyzed by immunohistochemical analysis in 36 HNSCC specimens and matched normal tissue control specimens harvested from the same patient. Western blot analysis was also performed on matched specimens to confirm the identity of the p63 isoforms that were found. In experiment 2, reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed on matched normal and tumor specimens to analyze and quantitatively compare p63 isoform expression at the RNA level. In experiment 3, p63 expression was evaluated by immunohistochemical analysis in oral lichen planus, a benign mucosal lesion marked by hyperdifferentiation and apoptosis. Methods: Immunohistochemical analysis, RT-PCR, and Western blot analysis of p63 were performed on HNSCC specimens and matched normal tissue control specimens. p63 expression in oral lichen planus specimens was also examined by immunohistochemical analysis. Results: In experiment 1, analysis of 36 HNSCC specimens from various head and neck subsites showed p63 expression in all tumors and matched normal tissue specimens (36 of 36). Western blot analyses indicated that dominant negative (,N) isoform p63, (,Np63,) is the major isoform expressed at the protein level in tumors and adjacent normal tissue. In experiment 2, RT-PCR analyses of 10 matched specimens confirmed that, although all three ,Np63 isoforms (,Np63,, ,Np63,, and ,Np63,) are expressed in normal and malignant mucosa of the head and neck, ,Np63, is the predominant transcript expressed. In experiment 3, immunohistochemical analysis of p63 in the pro-apoptotic condition of lichen planus indicated that p63 is underexpressed as compared with normal mucosal specimens. Conclusion: Although all three ,Np63 isoforms are present in HNSCC, ,Np63, protein is the predominant isoform expressed in these malignancies. ,Np63, is also overexpressed in tumors compared with matched normal tissue specimens and is underexpressed in the pro-apoptotic condition of lichen planus. These findings suggest that ,Np63, plays an anti-differentiation and anti-apoptotic role in the mucosal epithelium of the head and neck, possibly playing a pivotal role in the formation of HNSCC. Currently, ,Np63, is an attractive target for mechanistic study aimed at therapeutic intervention. [source] Palladium,Schiff base,triphenylphosphine catalyzed oxidation of alcoholsAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 9 2010Dileep R. Abstract Novel palladium(II)- N -(2-pyridyl)- N,-(5- R -salicylidene) hydrazine triphenylphosphine complexes were synthesized and characterized by UV, IR, 1H NMR and 31P NMR spectral analysis, C, H, N analysis and magnetic susceptibility measurements. The complexes were effective in the catalytic oxidation of primary and secondary alcohols in presence of N -methyl-morpholine- N -oxide as oxidant. The oxidation reactions were carried out in dichloromethane. A mechanistic study of the above reactions has been proposed. Copyright © 2010 John Wiley & Sons, Ltd. [source] Enhanced IFN, production in adenosine-treated CHOCells: A mechanistic studyBIOTECHNOLOGY PROGRESS, Issue 3 2009William P. K. Chong Abstract Adenosine causes growth arrest in recombinant mammalian cell cultures, which results in enhanced productivity of the recombinant protein. Adenosine is also known to increase intracellular ATP level when added to mammalian cells. As a cell's energy level affects its protein expression capacity, we investigated the factors that contribute to the increase in recombinant protein productivity. Chinese hamster ovary (CHO) cells expressing human interferon-gamma (IFN,) were treated with 1 mM adenosine on Day 2 of culture. The growth arrest resulted in 60% reduction in integral viable cell density when compared with control. However, IFN, titer improved 1.4-fold alongside a 2.5-fold increase in average specific productivity. The adenosine-treated cells also experienced a two-fold increase in ATP level that sustained for 3 days. Western blot studies revealed a relatively short-lived but strong activation of the energy sensor AMP-activated protein kinase (AMPK) in adenosine-treated cells. Activation of AMPK was probably due to adenosine being temporarily converted to AMP. Activated AMPK should have down-regulated protein translation by preventing mammalian target of rapamycin (mTOR) from phosphorylating and inactivating 4E-binding protein 1 (4E-BP1), a key repressor of protein translation initiation. However, Western blots showed increased phosphorylation of 4E-BP1 on Day 2 that lasted 3 days. This implied that a high concentration of ATP could keep 4E-BP1 inhibited, probably by directly modulating mTOR. This corroborated with an earlier in vitro observation (Dennis et al., Science. 2001;294:1102-1105). Inhibition of translation initiation repression is thus likely to contribute in part to the improvement in IFN,-specific productivity and titer. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Phosphine Ligands in the Palladium-Catalysed Methoxycarbonylation of Ethene: Insights into the Catalytic Cycle through an HP,NMR Spectroscopic StudyCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2010Verónica de, la Fuente Dipl.-Chem. Abstract Novel cis -1,2-bis(di- tert -butyl-phosphinomethyl) carbocyclic ligands 6,9 have been prepared and the corresponding palladium complexes [Pd(O3SCH3)(L-L)][O3SCH3] (L- L=diphosphine) 32,35 synthesised and characterised by NMR spectroscopy and X-ray diffraction. These diphosphine ligands give very active catalysts for the palladium-catalysed methoxycarbonylation of ethene. The activity varies with the size of the carbocyclic backbone, ligands 7 and 9, containing four- and six-membered ring backbones giving more active systems. The acid used as co-catalyst has a strong influence on the activity, with excess trifluoroacetic acid affording the highest conversion, whereas excess methyl sulfonic acid inhibits the catalytic system. An in operando NMR spectroscopic mechanistic study has established the catalytic cycle and resting state of the catalyst under operating reaction conditions. Although the catalysis follows the hydride pathway, the resting state is shown to be the hydride precursor complex [Pd(O3SCH3)(L- L)][O3SCH3], which demonstrates that an isolable/detectable hydride complex is not a prerequisite for this mechanism. [source] Facile Synthesis of Gold Octahedra by Direct Reduction of HAuCl4 in an Aqueous SolutionCHEMISTRY - AN ASIAN JOURNAL, Issue 6 2010Weiyang Li Abstract This paper describes a water-based protocol that provides a simple, convenient, and environmentally benign route to the synthesis of Au octahedra. Specifically, we obtained single-crystal Au octahedra (ca.,85,% of the product) with an edge length of 32.4±2.3,nm and singly twinned, truncated bipyramids (ca.,15,%) by reducing HAuCl4 with N -vinyl pyrrolidone in an aqueous solution in the presence of a proper amount of cetyltrimethylammonium chloride (CTAC). Our mechanistic study indicates that the formation of Au octahedra could be explained by oxidative etching, a pathway that has already been validated for the synthesis of nanocrystals for a number of different noble metals. [source] | ||||||||||||||||||||||||||||