The tautomerism of Omeprazole in solution: a 1H and 13C NMR study

The tautomerism of 5(6)-methoxy-2-([(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl] sulfinyl)-1H-benzimidazole (omeprazole) was determined in solution, K(T) = 0.59 in THF at 195 K, in favor of the 6-methoxy tautomer. The assignment of the signals was made by comparison with its two N-methyl derivatives in acetone-d6 and through theoretical calculations of the absolute shieldings (GIAO/DFT/6-311++G**).     

In vivo application of intestinal pH measurement using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) fluorescence imaging

Measurement of gastrointestinal intramucosal pH (pHim) has been recognized as an important factor in the detection of hypoxia-induced dysfunctions. However, current pH measurement techniques are limited in terms of time and spatial resolutions. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). This study aimed to set up and validate a fluorescence imaging technique to measure in vivo the intramucosal pH (pHim) of the intestine. The intestine was inserted into an optical chamber placed under a microscope. Animals were injected intravenously with the pH-sensitive fluorescent dye BCECF. Fluorescence was visualized by illuminating the intestine alternately at 490 and 470 nm. The emitted fluorescence was directed to an intensified camera. The ratio of emitted fluorescence at excitation wavelengths of 490 and 470 nm was measured, corrected and converted to pHim by constructing a calibration curve. The pHim controls were performed with a pH microelectrode and were correlated with venous blood gas sampling. Results show that pHim is determined with an accuracy of +/- 0.07 pH units and a response time of 1 min. In conclusion pHim mapping of rat intestine can be obtained by fluorescence imaging using BCECF. This technology could be easily adapted for endoscopic pH measurements.     

Estudios sobre ácidos hidroxámicos

Résumé On propose un procédé de microdosage des groupements méthoxyles dans les pectines, qui repose sur la libération de ces groupements par saponification de l'hydroxylamine alcoolique dans un appareil, sur leur transformation en formiates de méthyle et sur leur distillation. Le formiate de méthyle forme ainsi l'acide formhydroxamique que l'on dose par colorimétrie à l'état de chélate avec le fer-III.On réalise l'hydrolyse de la pectine à 100° C en tube scellé. On fait réagir avec l'acide formique en excès, une partie aliquote de l'hydrolysat dans le micro-appareil de distillation déjà décrit. Le procédé convient pour 1 à 3 mg de pectine et la durée des opérations est de deux heures et demies. Sa spécificité est satisfaisante bien que le groupe éthoxyle puisse gêner. Son action est d'ailleurs peu vraisemblable, puisqu'il ne fait pas partie de la molécule de pectine. Les résultats du procédé sont en générale un peu plus bas que ceux des méthodes volumétriques servant à ce dosage. On a étudié la reproductibilité pour les esters méthyliques et l'on a mis en évidence une erreur par défaut de 2 à 4%. Les plus petites quantités de groupes méthoxyles que l'on puisse doser sont de 20g. Le procédé recommandé est une application particulière de méthodes applicables de façon générale au dosage des esters méthyliques dans les substances organiques. Ce sera l'objet d'une autre communication de cette série.

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Summary A micromethod is given for determining methoxyl groups in pectins. It is based of the liberation of these groups by saponification, conversion into methyl formate, and distillation of the latter into a receiver containing alcoholic hydroxylamine. The methyl formate reacts to give formhydroxamic acid, which is determined colorimetrically as iron(III) chelate.The hydrolysis of the pectin is conducted at 100° C in a sealed tube. An aliquot part of the hydrolysate is brought into reaction with excess formic acid in a microdistillation apparatus that was described previously. The procedure is suitable for 1 to 3 mg pectin and requires 21/2 hours for all partial operations. The specificity is satisfactory, even though ethoxyl may interfere. However, this latter is not likely to be encountered since ethoxyl has not been shown to be a constituent of the pectin molecule. The results given by the procedure are in general inferior to those of volumetric methods. The reproducibility was tested on methyl esters and showed a minus error of 2 to 4%. The smallest amount of methoxyl which can be determined in this way is 20g. The method proposed here is a special application of a method which can be applied in general to the determination of methyl esters in organic substances, which will be the subject of a later paper in this series.

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Zusammenfassung Es wird ein Mikroverfahren zur Bestimmung der Methoxylgruppen in Pektinen angegeben, das auf der Freisetzung dieser Gruppen durch Verseifung, deren Umwandlung in Methylformiat und dessen Destillation in eine Vorlage von alkoholischem Hydroxylamin beruht. Das Methylformiat bildet damit Formhydroxamsäure, die als Eisen(III)-chelat kolorimetrisch bestimmt wird.Die Hydrolyse des Pektins wird bei 100° C in einem verschlossenen Rohr ausgeführt. Einen aliquoten Teil des Hydrolysates läßt man in einem schon früher beschriebenen Mikrodestillationsapparat mit überschüssiger Ameisensäure reagieren. Das Verfahren eignet sich für 1 bis 3 mg Pektin und erfordert für alle Teiloperationen 2^1/2 Stunden. Seine Spezifität ist befriedigend, obwohl Äthoxyl stören kann. Dessen Einwirkung ist jedoch wenig wahrscheinlich, da es nicht als Bestandteil des Pektinmoleküls nachgewiesen ist. Die Ergebnisse des Verfahrens sind im allgemeinen niedriger als die Resultate volumetrischer Methoden. Die Reproduzierbarkeit wurde an Methylestern überprüftund zeigte einen Minusfehler von 2 bis 4%. Die Mindestmenge bestimmbares Methoxyl beträgt 20g. Das vorgeschlagene Verfahren ist eine spezielle Anwendung einer allgemein für die Bestimmung von Methylestern in organischen Substanzen anwendbaren Methode, die Gegenstand einer weiteren Mitteilung dieser Serie sein wird.

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Resumen Se indica una microtécnica de valoración de metoxilos en pectinas, basada en la liberación del radical metilo éster por saponificación; en su conversion en formiato de metilo y en su simultanea destilación y recepción en hidroxilamina alcalinizada. El formiato de metilo se transforma así en ácido formohidroxámico, cuya determinación fotocolorimétrica se realiza como quelato férrico.Estas operaciones requieren efectuar la hidrólisis de la pectina en tubo cerrado y a 100° C, y en tomar una alícuota del hidrolizado, que se pasa con un exceso de ácido fórmico al aparato de microdestilación, detallado en comunicaciones anteriores. El método permite operar con 1 a 3 mg de pectina y todas las operaciones insumen unas dos y media horas. La técnica presenta condiciones satisfactorias de especificidad, pudiendo interferir los radicales etoxilos, cosa poco probable, pues no son reconocidos como componente de la molécula de pectina. Los resultados obtenidos, comparados con los del método titrimétrico, son por lo general inferiores a éste y su reproducibilidad, verificada con ésteres metílicos, tiene errores por defecto de un 2 a 4%. La cantidad mínima de metoxilo valorado alcanza a 20g. La técnica que se indica, es una aplicacion particular de otra de carácter general, aplicable a la valoración de ésteres metílicos en sustancias orgánicas, que será motivo de otra futura comunicación de esta serie.

     

Cure kinetics of epoxy resin and thermoplastic polymer

The cure kinetics and morphology of diglycidyl ether of bisphenol A (DGEBA) modified with polyvinyl acetate (PVAc) using diaminodiphenylmethane (DDM) as hardener were investigated through differential scanning calorimetry (DSC) and environmental scanning electron microscopy (ESEM). Isothermal curing measurements were carried out at 150, 120 and 80°C. The kinetic parameters were obtained using the general autocatalytic chemically controlled model. The comparison of the kinetic data indicates that the presence of PVAc does not change the autocatalytic nature of the cure reaction. Two T _g’s were observed in the fully cured samples of the modified systems. ESEM micrographies confirm the biphasic morphology.     

Kinetic study in water-ethylene glycol cationic, zwitterionic, nonionic, and anionic micellar solutions

The spontaneous hydrolysis of phenyl chloroformate was studied in water-ethylene glycol, EG, cationic, zwitterionic, nonionic, and anionic micellar solutions, the surfactants being tetradecyltrimethylammonium bromide, tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, tricosaoxyethylene glycol ether, and sodium dodecyl sulfate. The dependence of the observed rate constant on surfactant concentration as well as on the percentage by weight of EG, varying from 0 to 50 wt %, was investigated. Information about changes in the critical micelle concentrations, in the micellar ionization degrees (for ionic surfactants), in the aggregation numbers, and in the polarity of the interfacial region of the micelles upon changing the weight percent of EG was obtained through conductivity, surface tension, spectroscopic, and fluorescence measurements. A simple pseudophase model was adequate to rationalize the kinetic data. Micellar medium effects were explained by considering charge-charge interactions and polarity, ionic strength, and water content in the micellar interfacial region. The acceleration of the reaction produced by an increase in the amount of EG present in the mixture was explained on the basis of the substantial decrease in the equilibrium binding constant of phenyl chloroformate molecules to the micelles, resulting in the contribution of the reaction taking place in the bulk water-EG phase being more important. The weight percent of EG did not substantially influence the rate constant in the micellar pseudophase.     

Mono- and diboronates derived from tridentate ONO ligands and arylboronic acids

The syntheses of eight [4.3.0] heterobicyclic boronates containing a N → B coordinative bond are described. The monomeric compounds were prepared by reaction of arylboronic acids with a tridentate ligand having the ONO donor set of atoms. It was shown that substituents at the para-position of the B-phenyl moiety transmit electronic effects to the CN bond which in turn is polarized by formation of the N → B coordination bond. At the same time, related tridentate ligands were also reacted with 1,4-benzenediboronic acid in order to prepare benzene diboron complexes. The structure of this type of compounds was confirmed by X-ray analysis for one of the derivatives.     

Interaction of sodium cholate with dioctadecyldimethylammonium chloride vesicles in aqueous dispersion

Mixtures of dioctadecyldimethylammonium chloride (DODAC) cationic vesicle dispersions with aqueous micelle solutions of the anionic sodium cholate (NaC) were investigated by differential scanning calorimetry, DSC, turbidity and light scattering. Within the concentration range investigated (constant 1.0 mM DODAC and varying NaC concentration up to 4 mM), vesicle → micelle → aggregate transitions were observed. The turbidity of DODAC/NaC/water depends on time and NaC/DODAB molar concentration ratio R. At equilibrium, turbidity initially decreases smoothly with R to a low value (owing to the vesicle–micelle transition) when R = 0.5–0.8 and then increases steeply to a high value (owing to the micelle–aggregate transition) when R = 0.9–1.0. DSC thermograms exhibit a single and sharp endothermic peak at T_m ≈ 49 °C, characteristic of the melting temperature of neat DODAC vesicles in water. Upon addition of NaC, T_m initially decreases to vanish around R = 0.5, and the main transition peak broadens as R increases. For R > 1.0 two new (endo- and exothermic) peaks appear at lower temperatures indicating the formation of large aggregates since the dispersion is turbid. All samples are non-birefringent. Dynamic light scattering (DLS) data indicate that both DODAC and DODAC/NaC dispersions are highly polydisperse, and that the mean size of the aggregates tends to decrease as R increases.     

Synthesis of octahydroquinolines through the Lewis acid catalyzed reaction of vinyl allenes and imines

The reaction of vinyl allenes with imines under Lewis acid catalysis has been explored. Vinyl allenes in which the allenic portion of the molecule is tri- or tetrasubstituted gave octahydroquinoline derivatives as single isomers together with a minor compound formed by an ene reaction of the imine with the allene. Compounds in which the allene is 1,3-disubstituted do not react under the conditions assayed.     

Spectroscopic and photochemical properties of the lichen compound lobaric acid

Lichens synthesize and accumulate photoprotective compounds against possible damage induced by UV radiation in the photobiont. A biological model has been recently formulated that allows the use of lichens to evaluate changes at different UV radiation levels. The thermodynamics, photophysical and photochemical properties of lobaric acid were studied in acetonitrile, ethanol and Brij 35(3%) micelles at different pH values. Also the sun protector factor (SPF) was determined by in vitro methods. Lobaric acid was extracted from Stereoculon alpinum Laur. and characterized by means of standard procedures. Solutions were irradiated in oxygen and under nitrogen conditions with a UV medium pressure lamp. Lobaric acid absorbs at 287, 303 nm, and no fluorescence emission was observed. The maximum value of the molar extinction coefficient (5479.6 M(-1) cm(-1)) was obtained in Brij 35 at pH 12. Solubility is pH dependant and is highest in Brij 35 at pH 12 (4.45 x 10(-4) M). Photoconsumption quantum yields ranged between 10(-4) and 10(-5) in aerobic and anaerobic experimental conditions. Lobaric acid SPF was very low (0.5) compared with homosalate (4.0), (reference solar filter). Two pKa values, 5.05 (carboxylic acid group deprotonation) and 9.75 (phenolic OH deprotonation), were determined.     

Determination of metoprolol enantiomers in human urine by GC-MS using (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent

Summary A method for the assay of R-(+)- and S-(−)- metoprolol in human urine has been developed using gas chromatography-mass spectrometry. The method involved purification by liquid-liquid extraction and derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide to form an O-silyl ether, followed by subsequent chiral derivatization with (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride to form diastereomeric amide. The reaction was rapid and the diastereomeric derivatives were well resolved. Quantitation was performed by selected-ion monitoring of fragment ions of the diastereomers in electron impact ionization mode. No racemization was found during the reaction. The detection limit was 0.5 ng·mL⁻¹. The intra-day variation ranged between 0.38 and 7.86% in relation to the measured concentration and inter-day variation was 2.26–8.06%. The method has been applied to the determination of R-(+)-and S-(−)- metoprolol in human urine from healthy volunteers dosed with racemic metoprolol tartrate.