Synthesis of 2-amino-3-hydroxy- and of 2,3-diamino-3H-1,4-benzodiazepines

A new synthesis of 7-chloro-2,3-diamino-5-phenyl-3H-1,4-benzodiazepines is described, which allows for the preparation of compounds bearing the same or different substituents at the 2 and 3 positions, starting from 2-amino-7-chloro-3-hydroxy-5-phenyl-3H-1,4-benzodiazepines.     

Application of the DFT Theory to Study Cobalamin Complexes

The aim of present study is to select the best methodology in the frame of the Density Functional Theory (DFT), which may be employed to study the cobalamin complexes. Our discussion is limited to two approaches, one in which hybrid B3LYP and UB3LYP functionals are used, and the second in which geometry parameters are calculated within LDA-VWN functional, and energies of the investigated systems are computed within RPBE functional. Results of performed calculations show that both methodologies can be successfully applied to study cobalamin derivatives. Probably because of the small ligand binding energies in the studied complexes, the B3LYP and UB3LYP functionals may be used only to predict the pattern of changes in the binding energies. The use of the RPBE functional, originally parameterized to reproduce in a proper way the chemisorption energies of the small molecules on the metallic surfaces, allows to improve their values so as they fit into experimental data. Geometry parameters of the investigated complexes computed within both approaches are in good agreement with the experimental values. Interatomic distances are a little overestimated while calculated within both hybrid functionals, what is in contrast to VWN functional results. The latter, in general, gives shorter distances as observed experimentally.     

Behavior of Humic Acid as a Micellar Phase in Micellar Electrokinetic Chromatography (MEKC)

The possibility of humic acids acting as micellar phase in micellar electrokinetic chromatography was evaluated. We investigated the separation of naphthalene in capillary electrophoresis using various samples of humic acids as micellar phase under different pH conditions, concentrations of humic acid, and temperature. The humic acid samples studied were from different origins including peat, vermicompost and a commercial sample acquired from Aldrich. Methanol was used as a marker for the electroosmotic flow. The results indicate that the formation of micelle depends on the number and nature of the hydrophobic association sites in an aqueous humic acid solution and on the origin and concentration of the humic acid at a defined pH. At lower pH values, the possibility of the humic acid molecule forming pseudomicelles increases due to a combination of neutralized and dissociated charged sites.     

Metabonomics: the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development

The application of liquid chromatography/mass spectrometry (LC/MS) followed by principal components analysis (PCA) has been successfully applied to the screening of rat urine following the administration of three candidate pharmaceuticals. With this methodology it was possible to differentiate the control samples from the dosed samples and to identify the components of the mass spectrum responsible for the separation. These data clearly show that LC/MS is a viable alternative, or complementary, technique to proton NMR for metabonomics applications in drug discovery and development.     

Comparison of liquid chromatography-mass spectrometry interfaces for the analysis of polar metabolites of benz[a]pyrene

 The performance of two liquid chromatography-mass spectrometry (LC/MS) interfacing techniques, thermospray (TSP) and atmospheric pressure chemical ionization (APCI), for the analysis of benzo[a]pyrene (BaP) metabolites (hydroxy, epoxy and quinone derivatives) was compared. Interface and detection parameters such as source temperature, eluent composition or flow rate were optimized using negative ion mode. In TSP, the main ions are mostly [M]^-, [M−H₂O]^- or [M+CH₃COO]^-, whereas APCI gives mainly the [M]^- and [M−H]^- ions. Quantification was carried out by flow injection. Calibration graphs were linear in the range of 10 ng to 1000 ng in TSP and 0.1 ng to 10 ng in APCI. Detection limits were in the range of 1 ng to 20 ng in TSP and 0.002 ng to 0.2 ng in APCI. The presence of BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione was confirmed in environmental samples of air particulate matter. Received: 6 January 1997/Accepted: 18 April 1997     

VISIBLE CHEMILUMINESCENCE ASSOCIATED WITH THE REACTION BETWEEN METHEMOGLOBIN OR OXYHEMOGLOBIN WITH HYDROGEN PEROXIDE

Abstract Visible chemiluminescence is emitted in the irreversible deactivation of hemoglobin or methemoglobin with excess H₂O₂. The emission takes place in two phases. The most intense one lasts a few seconds and is followed by a second phase of lower intensity that remains for longer periods. This second phase presents chaotic or sustained oscillations. Free radicals are implicated in the luminescent process since the emission can be reduced by free radical scavengers such as 6-hydroxy-2,5,7,8,-tetramethylchroman-2-carboxylic acid (Trolox) or ascorbic acid. These additives lead to a delay in reaching the maximum intensity, which can be related to their consumption, implying substantial recycling of the hemoprotein. Chemiluminescence is also observed in the oxidation of hemin by H₂O₂, suggesting a role for the heme group in the processes leading to the excited state production. The lower intensity observed in the presence of hemin can be related to the contribution of the globin chains.     

Local and global chirality at surfaces: succinic acid versus tartaric acid on Cu110

A detailed comparison of tartaric acid (HOOC-CHOH-CHOH-COOH) and succinic acid (HOOC-CH(2)-CH(2)-COOH) molecules on a Cu(110) surface is presented with a view to elucidate how the two-dimensional chirality exhibited by such robust, chemisorbed systems is affected when both OH groups of the former molecule are replaced with H groups, a stereochemical change that leaves the metal-bonding functionalities of the molecule untouched but destroys both chiral centers. It is found that this change does not significantly affect the thermodynamically preferred chemical forms that are adopted, namely the doubly deprotonated bicarboxylate at low coverages (theta 相似文献   

Synthèse d'hétérocycles en catalyse par transfert de phase

A general study of the chemical behavior of heterocyclic anions, dianions and dianionic reagents under phase transfer catalysis conditions allowed us to synthesize various heterocyclic compounds such as imidazo[2,1-b]thiazole and derivatives; imidazo[2,1-b]thiazine and imidazo[2,1-b]benzothiazepine. Reaction conditions e.g., catalyst, solvent, temperature, etc., are indicated.     

Interaction of aryldiazonium salts with some schiff-base complexes of cobalt and ruthenium

The interaction of aryldiazonium ions with some Schiff-base complexes of cobalt and ruthenium have been studied. With cobalt, one-electron oxidation of [Co(II)Salen] occurred; with [Co(I)Salen] the corresponding Co(III)-aryl complexes were isolated. In the case of ruthenium oxidation also occurs, [Ru(Salen)(CO)py] gave the corresponding monocation. The results, especially for ruthenium, are in contrast to the stabilisation of both nitrosyl and aryldiazonium adducts in analogous porphyrin complexes.     

Liquid chromatographic retention behaviour and separation of promethazine and isopromethazine on a β-cyclodextrin bonded-phase column

A liquid chromatographic method for the separation of promethazine (PR) and its positional isomer isopromethazine (IPR) is described.PR is an N-substituted phenothiazine with the actions and the uses of the antihistamines (H1-receptor antagonists). IPR is an impurity in the pharmaceutical preparations of PR and must be controlled at a level below 1%. The liquid chromatographic behaviour of PR and IPR on a hydrolytically stable β-cyclodextrin (β-CD) column with respect to mobile phase composition, pH, ionic strength and the nature of the organic modifier was also investigated. Based on the results, conditions were chosen for the isocratic separation of the two isomers. The proposed separation method is simple and rapid and permits the simultaneous determination of PR and IPR. The separation selectivity of a cyclodextrin bonded-phase column was examined. Special attention was devoted to modelling the inclusion complexes of PR and IPR with β-CD in order to predict their optimum orientation within the β-CD cavity.