Functionalization of (2S)-Isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones by a Suzuki-Miyaura Cross-Coupling Reaction Using Aryltrifluoroborate Salts: Convenient Enantioselective Preparation of alpha-Substituted beta-Amino Acids

A simple protocol for the Pd(OAc)(2)-catalyzed cross-coupling reaction of 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones with potassium aryltrifluoroborates was developed. The reaction is performed at 110 degrees C with a ligand-free catalyst. In all cases, complete conversion of the 1-benzoyl-(2S)-isopropyl-5-iodo-2,3-dihydro-4(H)-pyrimidin-4-ones and aryltrifluoroborates into the C-C coupling products was observed within 30-360 min. It is noteworthy that a large variety of groups present in the potassium aryltrifluoroborates (-CF(3), -OMe, -SEt, -CN, -CHO, -Cl, -Cbz, -NCbz, -OH, -CO(2)H) could be tolerated. Hydrogenation of the endocyclic double bonds in the Suzuki-Miyaura products followed by acid hydrolysis afforded highly enantioenriched alpha-aryl-substituted beta-amino acids.

Hysteresis and phase transitions in a single partially internally wetted catalyst pellet: Thermogravimetric studies

The hydrogenation of cyclohexene over palladium supported in a microporous gamma-alumina pellet is studied thermogravimetrically with a view to measuring the extent of partial internal wetting associated with the different steady state branches. As many as three steady state branches having significantly different degrees of internal wetting and reaction rates, with transitions between them, are confirmed from observations of catalyst weight change. It is seen that with reduction in catalyst activity the middle branch, obtained by condensation from a vapor filled pellet, is much more prominent without showing an evaporative transition for the range of hydrogen partial pressures used here. The catalyst activity is therefore an important parameter affecting the structure of the steady state branches. Hysteresis effects are found to occur, and the thermogravimetric results also confirm the importance of history in determining the catalyst state. The measured degree of wetting is in accordance with that estimated from a mathematical model incorporating capillary condensation effects in addition to reaction-diffusion phenomena. The same model also satisfactorily interprets the reaction rate variations and transitions seen in the present work.

Preparation, characterization, and catalytic properties of clay-based nickel catalysts for methane reforming

Naturally occurring clays and pillared clays are used as supports of nickel catalysts for the methane reforming reaction with carbon dioxide to synthesis gas. The structural and textural characteristics of the supports and catalysts are systematically examined by N-2 adsorption/desorption and X-ray diffraction (XRD) techniques. It is found that the pore structures and surface properties of supports greatly affect the catalytic activities of the catalysts prepared. The catalysts supported on the mesoporous clays or pillared clays are obviously superior to those on microporous supports because the mesoporous supports are highly thermal stable compared to the microporous ones. It is found that introducing lanthanum to the supports can improve the catalyst basicity and thus enhance the catalytic activities of these catalysts. Deactivation of catalysts prepared and factors influencing their stability are also discussed. (C) 1998 Academic Press.

A comprehensive study on carbon dioxide reforming of methane over Ni/gamma-Al2O3 catalysts

Carbon dioxide reforming of methane into syngas over Ni/gamma-Al2O3 catalysts was systematically studied. Effects of reaction parameters on catalytic activity and carbon deposition over Ni/gamma-Al2O3 catalysts were investigated. It is found that reduced NiA1204, metal nickel, and active species of carbon deposited were the active sites for this reaction. Carbon deposition on Ni/gamma Al2O3 varied depending on the nickel loading and reaction temperature and is the major cause of catalyst deactivation. Higher nickel loading produced more coke on the catalysts, resulting in rapid deactivation and plugging of the reactor. At 5 wt % Ni/gamma-Al2O3 catalyst exhibited high activity and much lesser magnitude of deactivation in 140 h. Characterization of carbon deposits on the catalyst surface revealed that there are two kinds of carbon species (oxidized and -C-C-) formed during the reaction and they showed different reactivities toward hydrogenation and oxidation. Kinetic studies showed that the activation energy for CO production in this reaction amounted to 80 kJ/mol and the rate of CO production could be described by a Langmuir-Hinshelwood model.

Synthesis of homoallylic oxygenated alpha-methylene-gamma-butyrolactones: a model for preparing biologically active natural lactones

In this Letter we describe a 12% overall yield synthesis of a model for homoallylic oxygenated alpha-methylene-gamma-butyrolactones with relative stereochemistry defined by selective hydrogenation with Rh/Al(2)O(3). The synthesis was realized in 9 steps involving simple reactions. (C) 2008 Elsevier Ltd. All rights reserved.

Jacobsen catalyst immobilized on chitosan membrane as interface catalyst in organic/aqueous system for alkene oxidation

The Jacobsen catalyst, Mn(salen), was immobilized in chitosan membrane. The obtained Mn(salen)-Chit was characterized by thermogravimetric analysis (TC), differential thermal analysis (DTA), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), degree of N-acetylation by (1)H NMR, and UV-vis spectroscopy. The UV-vis absorption spectrum of the encapsulated catalyst displayed the typical bands of the Jacobsen catalyst, and the FT-IR presented an absorption band characteristic of the imines present in the Jacobsen catalyst. The chitosan membranes were available, in a biphasic system, as a catalytic barrier between two different phases: an organic substrate phase (cyclooctene or styrene) and an aqueous solution of either m-CPBA, t-BuOOH or H(2)O(2), and dismissing the need for phase transfer agents and leading to better product yields compared with the catalyst in homogeneous medium. This new catalyst did not leach from the support and was reused many times, leading to high turnover frequencies. (C) 2009 Elsevier B.V. All rights reserved.

n-Hexane hydroisomerisation over bifunctional Pt/MCM-22 catalysts. Influence of the mode of Pt introduction

Three different methods were used to introduce 1.0 wt.% of Pt in bifunctional Pt/MCM-22 zeolite catalysts: ion exchange with Pt(NH3)(4)(2+), incipient wetness impregnation with PtCl6H2 and mechanical mixture with Pt/Al2O3. The Pt dispersion was estimated by transmission electron microscopy and the hydrogenating activity with toluene hydrogenation at 110 degrees C. From these experiments, it can be concluded that with the ion exchanged sample, platinum was located within the inner micropores and on the outer surface, whereas with the impregnated one, platinum was essentially on the outer surface under the form of large particles. With all the samples there is a fast initial decrease in the activity for n-hexane hydroisomerisation at 250 degrees C. With exchanged and impregnated samples, this decrease is followed by a plateau, the activity value being then higher with impregnated sample. For the sample prepared by mechanical mixture a continuous decrease in activity can be observed. All these differences can be related with the distinct locations of Pt.

Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl-Derived Complexes with Nitrogen Coordinated Ligands

Four cationic ruthenium(II) complexes with the formula [Ru(eta(5)-C5H5)(PPh3)(2)](+), with L = 5-phenyl-1H-tetrazole (TzH) 1, imidazole (ImH) 2, benzo[1,2-b; 4,3-b'] dithio-phen-2-carbonitrile (Bzt) 3, and [5-(2-thiophen-2-yl)-vinyl]-thiophene-2-carbonitrile] (Tvt) 4 were prepared and characterized in view to evaluate their potentialities as antitumor agents. Studies by Circular Dichroism indicated changes in the secondary structure of ct-DNA. Changes in the tertiary structure of pBR322 plasmid DNA were also observed in gel electrophoresis experiment and the images obtained by atomic force microscopy (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing of the viscosity with time indicates that the complexes do not intercalate between DNA base pairs. Compounds 1, 2, and 3 showed much higher cytotoxicity than the cisplatin against human leukaemia cancer cells (HL-60 cells).

Extraction of hemoglobin with calixarenes and biocatalysis in organic media of the complex with pseudoactivity of peroxidase

The present work involves the use of p-tert-butylcalix[4,6,8]arene carboxylic acid derivatives ((t)Butyl[4,6,8]CH2COOH) for selective extraction of hemoglobin. All three calixarenes extracted hemoglobin into the organic phase, exhibiting extraction parameters higher than 0.90. Evaluation of the solvent accessible positively charged amino acid side chains of hemoglobin (PDB entry 1XZ2) revealed that there are 8 arginine, 44 lysine and 30 histidine residues on the protein surface which may be involved in the interactions with the calixarene molecules. The hemoglobin-(t)Butyl[6]CH2COOH complex had pseudoperoxidase activity which catalysed the oxidation of syringaldazine in the presence of hydrogen peroxide in organic medium containing chloroform. The effect of pH, protein and substrate concentrations on biocatalysis was investigated using the hemoglobin-(t)Butyl[6]CH2COOH complex. This complex exhibited the highest specific activity of 9.92 x 10(-2) U mg protein(-1) at an initial pH of 7.5 in organic medium. Apparent kinetic parameters (V'(max), K'(m), k'(cat) and k'(cat)/K'(m)) for the pseudoperoxidase activity were determined in organic media for different pH values from a Michaelis-Menten plot. Furthermore, the stability of the protein-calixarene complex was investigated for different initial pH values and half-life (t(1/2)) values were obtained in the range of 1.96 and 2.64 days. Hemoglobin-calixarene complex present in organic medium was recovered in fresh aqueous solutions at alkaline pH, with a recovery of pseudoperoxidase activity of over 100%. These results strongly suggest that the use of calixarene derivatives is an alternative technique for protein extraction and solubilisation in organic media for biocatalysis.

Coordination Chemistry of the (eta(6)-p-Cymene)ruthenium(II) Fragment with Bis-, Tris-, andTetrakis(pyrazol-1-yl)borate Ligands: Synthesis, Structural, Electrochemical, and CatalyticDiastereoselective Nitroaldol Reaction Studies

Novel [Ru(eta(6)-p-cymene)(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O complexes (L = bis-, tris-, or tetrakis-pyrazolylborate; X = Cl, N-3, PF6, or CF3SO3) are prepared by treatment of [Ru(eta(6)-p-cymene)Cl-2](2) with poly-(pyrazolyl)borate derivatives [M(L)] (L in general; in detail L = Ph(2)Bp = diphenylbis-(pyrazol-1-yl)borate; L = Tp = hydrotris(pyrazol-1-yl)borate; L = pzTp = tetrakis(pyrazol-1-yl)borate; L = Tp(4Bo) = hydrotris(indazol-1-yl)borate, L = T-p4Bo,T-5Me = (5-methylindazol-1-yl)borate; L = Tp(Bn,4Ph) = hydrotris(3-benzyl-4-phenylpyrazol-1-yl)borate; M = Na, K, or TI) and characterized by analytical and spectral data (IR, ESIMS, H-1 and C-13 NMR). The structures of [Ru(eta(6)-p-cymene)(Ph(2)Bp)Cl] (1) and [Ru(eta(6)-p-cymene)(Tp)Cl] (3) have been established by single-crystal X-ray diffraction analysis. Electrochemical studies allowed comparing the electron-donor characters of Tp and related ligands and estimating the corresponding values of the Lever E-L ligand parameter. The complexes [Ru(eta(6)-p-cymene)-(kappa(2)-L)X] and [Ru(eta(6)-p-cymene)(kappa(3)-L)]X center dot nH(2)O act as catalyst precursors for the diastereoselective nitroaldol reaction of benzaldehyde and nitroethane to the corresponding beta-nitroalkanol (up to 82% yield, at room temperature) with diastereoselectivity toward the formation of the threo isomer.

DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl derivative complexescontaining heteroaromatic ligands

Four ruthenium(II) complexes with the formula [Ru(eta(5)-C(5)H(5))(PP)L][CF(3)SO(3)], being (PP = two triphenylphosphine molecules), L = 1-benzylimidazole, 1; (PP = two triphenylphosphine molecules), L = 2,2'bipyridine, 2; (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, 3; (PP = 1,2-bis(diphenylphosphine) ethane), L = 4-Methylpyridine, 4, were prepared, in view to evaluate their potentialities as antitumor agents. The compounds were completely characterized by NMR spectroscopy and their crystal and molecular structures were determined by X-ray diffraction. Electrochemical studies were carried out giving for all the compounds quasi-reversible processes. The images obtained by atomic force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements of the viscosity of solutions of free DNA and DNA incubated with different concentrations of the compounds confirmed this interaction. The cytotoxicity of compounds 1234 was much higher than that of cisplatin against human leukemia cancer cells (HL-60 cells). IC(50) values for all the compounds are in the range of submicromolar amounts. Apoptotic death percentage was also studied resulting similar than that of cisplatin. (C) 2010 Elsevier Inc. All rights reserved.

Study of Pt/MCM-22 based catalysts in the transformation of n-hexane: effect of rare earth elements and mode of platinum introduction

The bifunctional transformation of n-hexane was carried out over Pt/MCM-22 based catalysts. MCM-22 was synthesized and submitted to ion exchange with rare earth nitrate solutions of La, Nd and Yb, followed by Pt introduction. Three different methods were used to introduce about 1 wt% of Pt in the zeolite: ion exchange, incipient wetness impregnation and mechanical mixture with Pt/Al(2)O(3). The bifunctional catalysts were characterized by transmission electron microscopy and by the model reaction of toluene hydrogenation. These experiments showed that, in the ion exchanged sample, Pt is located both within the inner micropores and on the outer surface, whereas in the impregnated one, the metal is essentially located on the outer surface under the form of large particles. The presence of RE elements increases the hydrogenating activity of Pt/MCM-22 since the location of these species at the vicinity of metal particles causes modification on its electronic properties. Whatever the mode of Pt introduction, a fast initial decrease in conversion is observed for n-hexane transformation, followed by a plateau related to the occurrence of the catalytic transformations at the hemicages located at the outer surface of the crystals. The effect of rare earth elements on the hydrogenating function leads to a lower selectivity in dibranched isomers and increased amounts of light products.

Biological activity and cellular uptake of [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complex

Anticancer activity of the new [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine) complex was evaluated in vitro against several human cancer cell lines, namely A2780, A2780CisR, HT29, MCF7, MDAMB231 and PC3. Remarkably, the IC50 values, placed in the nanomolar and sub-micromolar range, largely exceeded the activity of cisplatin. Binding to human serum albumin, either HSA (human serum albumin) or HSA(faf) (fatty acid-free human serum albumin) does not affect the complex activity. Fluorescence studies revealed that the present ruthenium complex strongly quench the intrinsic fluorescence of albumin. Cell death by the [Ru(eta(5)-C5H5)(PPh3)(Me(2)bpy)][CF3SO3] complex was reduced in the presence of endocytosis modulators and at low temperature, suggesting an energy-dependent mechanism consistent with endocytosis. On the whole, the biological activity evaluated herein suggests that the complex could be a promising anticancer agent. (C) 2013 Elsevier Inc. All rights reserved.

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(eta(6)-cymene)(bha)Cl] complexes

The ruthenium(II)-cymene complexes [Ru(eta(6)-cymene)(bha)Cl] with substituted halogenobenzohydroxamato (bha) ligands (substituents = 4-F, 4-Cl, 4-Br, 2,4-F-2, 3,4-F-2, 2,5-F-2, 2,6-F-2) have been synthesized and characterized by elemental analysis, IR, H-1 NMR, C-13 NMR, cyclic voltammetry and controlled-potential electrolysis, and density functional theory (DFT) studies. The compositions of their frontier molecular orbitals (MOs) were established by DFT calculations, and the oxidation and reduction potentials are shown to follow the orders of the estimated vertical ionization potential and electron affinity, respectively. The electrochemical E-L Lever parameter is estimated for the first time for the various bha ligands, which can thus be ordered according to their electron-donor character. All complexes exhibit very strong protein tyrosine kinase (PTK) inhibitory activity, even much higher than that of genistein, the clinically used PTK inhibitory drug. The complex containing the 2,4-difluorobenzohydroxamato ligand is the most active one, and the dependences of the PTK activity of the complexes and of their redox potentials on the ring substituents are discussed. (C) 2012 Elsevier B.V. All rights reserved.

Novos receptores moleculares baseados em calix[4]arenos: aplicação à química sensorial

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Química