Utility of certain pi-acceptors for the spectrophotometric determination of some penicillins

Two simple and sensitive spectrophotometric methods are described for the determination of six penicillin derivatives. The methods are based on the reaction of these drugs as n-electron donors with either 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) or 7,7,8,8-tetracyanoquinodimethane (TCNQ) as pi-acceptors, to give a highly coloured radical anion. The coloured products are quantified spectrophotometrically at 460 and 842 nm for DDQ and TCNQ, respectively. The optimization of the different experimental conditions is described. The interference from streptomycin sulphate and common degradation products was also studied. The proposed methods were applied successfully to the determination of the different penicillins investigated, either in pure or dosage forms, with good accuracy and precision. The results were compared with those given by the official United States Pharmacopeial XXI method.     

The influence of cosolvent polarity on the flow properties of hydroalcoholic gels: empirical models

The aim of this study was to investigate the influence of cosolvent polarity on the rheological flow properties of aqueous and hydroalcoholic gels obtained from the Carbopol Ultrez 10 base and used for topical applications. Specifically, we have examined the effect of pH (range 4.0--7.0) on the consistency and flow properties of dispersed systems in water and mixtures--15 : 85% v/v of methanol : water, ethanol : water, n-propanol : water and n-butanol : water--at a constant polymer concentration of 0.3% w/w. The gels, which had decreasing polarity values in the jellifying medium, showed qualitatively similar flow behavior, characteristic of pseudoplastic systems, and all of the flow curves were adjusted to the Ostwald model. Sigmoidal dose response functions were calculated to describe the flow and consistency indexes as a function of pH. As a result, the influence of alcohol polarity on the polymer network has been assessed meaningfully using the empirical parameters obtained: maximum consistency index value (k(max)), pH value required for 50% development of polymer network (pH(50)), and asymptotic flow index value (n(min)) for the fully structured gels.     

Excess molar enthalpy of binary mixtures of hexane+ethyl benzene, <Emphasis Type="Italic">o</Emphasis>-xylene, <Emphasis Type="Italic">m</Emphasis>-xylene and <Emphasis Type="Italic">p</Emphasis>-xylene at 298.15 K

Summary This paper reports excess molar enthalpies of the binary systems hexane+ethyl benzene, hexane+o-xylene, hexane+m-xylene and hexane+p-xylene at 298.15 K and atmospheric pressure, over the whole composition range. The data was measured directly using a Calvet microcalorimeter. The excess magnitude was correlated to a Redlich-Kister type equation for each mixture. Also, we will discuss the results for the four mixtures studied here and by comparison with the same binary systems but containing propyl propanoate as first component. Finally, we will correlate our results with the Nitta-Chao and the three UNIFAC theoretical approximations.     

Solubility and first hidrolysis constants of europium at different ionic strength and 303 K

The solubility of europium at 0.02M, 0.1M and 0.7M NaClO₄ ionic strength solutions was determined by a radiometric method and pEu_s-pC_H diagrams were obtained. Hydrolysis constants were also determined at the same ionic strengths by pH titration and the values found were log *₁ = -7.68±0.11, -8.07±0.10 and -8.20±0.11. The log K _sp values were -23.5±0.2, -22.7±0.2 and -21.9±0.2 for 0.02M, 0.1M and 0.7M NaClO₄ ionic strengths, respectively, at 303 K under CO₂-free conditions and the extrapolated value at zero ionic strength was log K _sp ⁰ = -24.15. The working pC_H ranges for the calculation of the hydrolysis constants were selected from the pEu_s-pC_H diagrams in the region where precipitation of europium oxide or hydroxide was less than 20%. Europium removal from aqueous solutions with zeolites was explored.     

Carbohydrate chain of ganglioside GM1 as a ligand: identification of the binding strategies of three 15 mer peptides and their divergence from the binding modes of growth-regulatory galectin-1 and cholera toxin

The branched pentasaccharide chain of ganglioside GM1 is a prominent cell surface ligand, for example, for cholera toxin or tumor growth-regulatory homodimeric galectins. This activity profile via protein recognition prompted us to examine the binding properties of peptides with this specificity. Our study provides insights into the mechanism of molecular interaction of this thus far unexplored size limit of the protein part. We used three pentadecapeptides in a combined approach of mass spectrometry, NMR spectroscopy and molecular modelling to analyze the ligand binding in solution. Availability of charged and hydrophobic functionalities affected the intramolecular flexibility of the peptides differently. Backfolding led to restrictions in two cases; the flexibility was not reduced significantly by association of the ligand in its energetically privileged conformations. Major contributions to the interaction energy arise from the sialic acid moiety contacting Arg/Lys residues and the N-terminal charge. Considerable involvement of stacking between the monovalent ligand and aromatic rings could not be detected. This carbohydrate binding strategy is similar to how an adenoviral fiber knob targets sialylated glycans. Rational manipulation for an affinity enhancement can now be directed to reduce the flexibility, exploit the potential for stacking and acquire the cross-linking capacity of the natural lectins by peptide attachment to a suitable scaffold.     

Solid-phase synthesis of the cyclic lipononadepsipeptide [N-Mst(Ser1), d-Ser4, L-Thr6, L-Asp8, L-Thr9]syringotoxin

An optimized solid-phase strategy for the preparation of the cyclic lipononadepsipeptide [N-Mst(L-Ser1), D-Ser4, L-Thr6, L-Asp8, L-Thr9]syringotoxin is reported. The strategy is based on the use of a mild orthogonal protection scheme and the incorporation of the nonproteinogenic amino acid (Z)-Dhb into the peptide chain as the dipeptide Fmoc-Thr(tBu)-(Z)-Dhb-OH. The didehydrodipeptide was synthesized by a water-soluble carbodiimide-induced beta-elimination of a protected dipeptide containing a residue of Thr with its free hydroxy side chain unprotected.     

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.

     

Enthalpies of formation of methoxybenzoic acids and their dependence on structure

The energy of combustion of 2,5-dimethoxybenzoic acid has been determined using a static bomb calorimeter. The vapor pressures of the compound have been measured over a 18 K temperature interval by the Knudsen effusion technique. Heat capacity measurements betweenT=270 K andT=338 K were carried out by DSC. From these experimental results the standard molar enthalpies of combustion, sublimation, and formation in the crystalline and gaseous state at the temperature 298.15 K have been derived. With this compound, the series of mono- and dimethoxy-benzoic acids have been completed. Their_f H _m ^o values were expressed by an additive relationship, taking into account the number of methoxy groups and the number of all 1,2 interactions: an accuracy of 3.3 kJ·mol^–1 was achieved. In an alternative approach the substituent effect of the methoxy groups was evaluated within the framework of isodesmic reactions. The effect of disubstitution was referred to mono derivatives and the excess energy—the so-called buttressing effect—was evaluated (2–24 kJ· mol^–1 for individual bis derivatives). These values were explained in terms of the conformation of the methoxy group around the C_ar-O bond.     

In situ assembled ZIF superstructures via an emulsion-free soft-templating approach

Assembling well-defined MOF superstructures remains challenging as it requires easily removable hard templates or readily available immiscible solutions for an emulsion-based soft-template approach. In this work, a single-step emulsion-free soft templating approach is reported to spontaneously prepare hollow ZIF-8 and ZIF-67 colloidosomes with no further purification. These superstructures can load different enzymes regardless of the size and charge with a high encapsulation efficiency of 99%. We envisage that this work will expand the repertoires of MOF superstructures by the judicious selection of precursors and the reaction medium.

An emulsion-free approach for the preparation of hollow ZIF-8 superstructures in a single step is established based on metal sulfate hydrates in methanol.