Rapid, low pressure, and simultaneous ion chromatography of common inorganic anions and cations on short permanently coated monolithic columns

Short permanently coated reversed-phase silica based monolithic columns have been investigated for the rapid separation of inorganic anions and cations. One 2.5 x 0.46 cm column was permanently coated with didodecyldimethylammonium (DDAB), for anion analysis; and a second 5.0 x 0.46 cm column was coated with dioctylsulphosuccinnate (DOSS), for cation analysis. The use of a single combined eluent of 2.5 mM phthalate/1.5 mM ethylenediamine, at flow rates of between 4.0 and 8.0 mL/min, resulted in the rapid separation of 8 anions (in under 100 s) and 5 cations (in under 100 s) on the above columns when used individually, with detection limits for common anions ranging from approximately 0.25 to 5 mg/L, and between 2.5 and 50 mg/L for alkaline earth metals, by direct and indirect conductivity detection, respectively. However, with both columns subsequently connected in parallel, with the eluent delivered using a flow splitter from a single isocratic pump, the simultaneous analysis of anions and cations was also possible, based on a single conductivity detector. The potential of this system for the rapid, complete screening of water samples for multiple common anions and cations is shown.     

Intramolecular Diels-Alder and tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reactions of 1,3,4-oxadiazoles

The scope of intramolecular Diels-Alder and a novel tandem Diels-Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles is disclosed. In the cases examined, the tandem cycloadditions construct three new rings with formation of four new C-C bonds and set all six stereocenters about a central six-membered ring in a single step including three contiguous and four total quaternary centers without a trace of a second diastereomer.     

Steady flux in a continuous-space Sinai chain

We examine the steady-state flux of particles diffusing in a one-dimensional finite chain with Sinai-type disorder, i.e., the system in which in addition to the thermal noise, particles are subject to a stationary random-correlated in space Gaussian force. For this model we calculate the disorder average (over configurations of the random force) flux exactly for arbitrary values of system's parameters, such as chain lengthN, strength of the force, and temperature. We prove that within the limitN1 the average flux decreases withN as J(N)=C/N and thus confirm our recent predictions that the flux in the discrete-space Sinai model is anomalous.     

Star-shaped azo-based dipolar chromophores: design, synthesis, matrix compatibility, and electro-optic activity

Three new azo-benzene-based push-pull chromophores with dendritic architecture were synthesized as active materials for electro-optic applications. These chromophores were synthesized in six or seven synthetic steps with an overall yield of around 80% per step and high purity. UV-vis spectroscopy showed significant influence of the transient dipole moment on the observed r(33) values. The chromophores were stable to photochemical oxidation in ambient light and air. The electrical poling conditions were optimized for each chromophore as the T(g) of the composite material varied significantly. The highest EO coefficient achieved was 22-25 pm/V at 1550 nm wavelength. STEM analysis of the blends enabled the correlation of the activity of these large chromophores with the blend morphology. An amorphous polycarbonate host effectively disperses the chromophores in 2-20 nm aggregates in the active materials. However, macrophase separation into 200-500 nm aggregates was observed in a methacrylate host matrix.     

Separation and identification of the 4-hydroxyantipyrine sulphoconjugate.

In a previous study we observed, during separation of total antipyrine metabolites by high-performance liquid chromatography and after enzymatic hydrolysis, an unidentified peak corresponding to an ionic compound with pyrazolinone features. In the present study, this compound was identified as the 4-hydroxyantipyrine sulphoconjugate, and its structure was definitively confirmed by gas chromatographic-mass spectrometric analysis and by the use of pure synthetic substance. We also demonstrated the inhibitory effect of sodium metabisulphite, a necessary preservative of urinary samples, on hydrolysis of this conjugate in the presence of sulphatases from Helix pomatia or Aerobacter aerogenes. This inhibitory effect makes it impossible to perform a global assay of antipyrine metabolites after enzymatic or chemical hydrolysis and confirms the value of direct assay of the 4-hydroxyantipyrine sulphoconjugate.     

Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition

Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.     

Comparison of quantitative methods for analysis of polyphasic pharmaceuticals

Adequate very sensitive quantification methods are needed for the development and are also now required for the monitoring of undesirable solid form(s) as routine tests. The pre-requisite for quantitation are selectivity, sensitivity and most important the purity of standards and their proper storage, what is a challenge for metastable forms. Several analytical techniques are available such as X-ray diffraction, spectroscopy, thermal analysis and microcalorimetry. The different steps of the validation of the analytical methods and problems to be solved are discussed. Examples illustrate the different techniques and compare their possible advantages and limits. The relative standard deviation of measurements should allow for checking the homogenization procedure of mixtures for calibration. The validation should be carried out following ICH guidelines for validation of analytical methods. Comparison of different techniques in adequate concentration range add confidence in the analytical results.     

Highly efficient antibody-catalyzed deuteration of carbonyl compounds

Antibody 38C2 efficiently catalyzes deuterium-exchange reactions at the alpha position of a variety of ketones and aldehydes, including substrates that have a variety of sensitive functional groups. In addition to the regio- and chemoselectivity of these reactions, the catalytic rates (kcat) and rate-enhancement values (kcat/kun) are among the highest values ever observed with catalytic antibodies. Comparison of the substrate range of the catalytic antibody with highly evolved aldolase enzymes, such as rabbit-muscle aldolase, highlights the much broader practical scope of the antibody, which accepts a wide range of substrates. The hydrogen-exchange reaction was used for calibration and mapping of the antibody active site. Isotope-exchange experiments with cycloheptanone reveal that the formation of the Schiff base species (as concluded from the 16O/18O exchange rate at the carbonyl oxygen) is much faster than the formation of the enamine intermediate (as concluded from the H/D exchange rate), and both steps are faster than the antibody-catalyzed aldol addition reaction.     

Structure du radical cyano-vinyle CH2=Ċ-CN Etude expérimentale et théorique

Résumé Tout d'abord, on montre par RPE que le radical CH₂=-CN possède à basse température une structure instable pliée et à température plus élevée une structure stable linéaire. Un calcul théorique sur ce radical ainsi que sur le radical butatriényle est en bon accord avec les résultats expérimentaux.

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The structure of the Cyano-Vinyl Radical CH₂=-CN experimental and theoretical study

First, it is shown by ESR that the radical CH₂=-CN at low temperature presents an unstable bent structure and at higher temperature a stable linear structure. A theoretical calculation on this radical and on the butatrienyl one is in good agreement with the experimental results.

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Zusammenfassung Aus ESR Messungen wird gefolgert, daß das Radikal CH₂=-CN bei tiefer Temperatur in einer instabilen gebogenen Struktur und bei höherer Temperatur in einer stabilen linearen Struktur vorliegt. Theoretische Berechnungen stehen sowohl für dieses als auch für das Butatrienyl-Radikal in guter Übereinstimmung mit experimentellen Daten.