Synthesis of simplified hybrid inhibitors of type 1 17beta-hydroxysteroid dehydrogenase via cross-metathesis and sonogashira coupling Reactions

[structure: see text] The inhibitor of type 1 17beta-hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a Sonogashira coupling reaction as key steps is described. Compounds 2a-c were also tested as enzyme inhibitors and compared to EM-1745.     

Experimental design optimization of the analysis of gasoline by capillary gas chromatography

An optimization procedure for multi-step temperature programmed capillary GC was investigated for the detailed hydrocarbon analysis of gasoline. A set of twelve responses, represented by the value of the resolution of the most difficult separations, was selected from several isothermal analyses. The variation of these responses versus the temperature programming conditions was then modeled using a Doehlert matrix for experimental design. Optimal experimental conditions for the twelve responses were then obtained from a response surface optimization. The predicted and experimental resolutions were in good agreement.     

Transmission surface-plasmon resonance (T-SPR) measurements for monitoring adsorption on ultrathin gold island films

Evaporation of ultrathin (1.3-10 nm nominal thickness) gold films onto quartz or mica leads to the formation of a layer of rather uniform gold islands on the transparent support. The morphology of ultrathin gold island films of various thicknesses was studied by using atomic force microscopy (AFM) and scanning electron microscopy (SEM) imaging. The surface plasmon (SP) absorption characteristic of such films is highly sensitive to the surrounding medium, with the plasmon band changing in intensity and wavelength upon binding of various molecules to the surface. The binding process can be monitored quantitatively by measuring the changes in the gold SP absorption, by using transmission UV/Vis spectroscopy. The method, termed transmission surface plasmon resonance (T-SPR) spectroscopy, is shown to be applicable to both chemically and physically adsorbed molecules, in liquid or gas phase, with measurements carried out either ex situ or in situ (real-time measurements) using a variety of molecular probes. Binding to a preformed molecular layer on the Au surface produces a similar response, suggesting the possible use of T-SPR for selective sensing. The sensitivity of T-SPR spectroscopy in detecting molecular binding to the gold depends strongly on the film preparation conditions, and may be comparable to that obtained in surface plasmon resonance (SPR) sensing.     

Control of n-alkanes crystallization by ethylene-vinyl acetate copolymers

The crystallization of paraffins from their solution at low temperature was investigated in the presence of ethylene-vinyl acetate (EVA) copolymers that allow the control of the size of the crystals. Depending on the type of solvent and distribution of the paraffin lengths, the mechanisms of crystal formation and growth are different. Precipitation of the EVA prior to the paraffins leads to the nucleation of a large number of crystals, whereas the adsorption of EVA on the surface of the growing crystals slows down the crystal growth. EVA can act either as a nucleating agent or as a growth inhibitor. These two mechanisms were identified from the analysis of the temperature of crystallization (cloud point), the chemical composition of the crystals, and the observations of the crystal habit. The EVA was able to co-crystallize with the paraffins in crystals of an orthorhombic structure and the melting enthalpies of the crystalline paraffin did not depend significantly on their neighborhood. The energies of interaction between the different paraffinlike components are close to each other, so that minor changes of the experimental conditions may lead to dramatic effects. This is the basic rationale for the large behavioral diversity observed in these systems.     

Synthesis of 9-substituted-1,4,5,8-tetraazaphenanthrenes

The synthesis of 9-substituted-1,4,5,8-tetraazaphenanthrenes was undertaken in the course of a study aimed at the preparation of organometallic complexing agents.     

Protein purification using combined streptavidin (or avidin)-Sepharose and thiopropyl-Sepharose affinity chromatography.

The major problem usually encountered in the application of the (strept)avidin-biotin system to the purification of proteins (or other biological molecules) lies in the difficult reversion of the interaction between immobilized (strept)avidin and the adsorbed biotinylated protein. Among the proposed solutions is the selective biotinylation of the entity to be purified by a disulphide-containing biotinylated reagent which allows its recovery from (strept)avidin gels by dithiothreitol (DTT) treatment. As emphasized by the example of angiotensin II receptor purification, achieved using this strategy, optimum reduction of this disulphide bridge may require improvement of its accessibility using denaturating agents such as sodium dodecyl sulphate or urea. However, these agents release important amounts of (strept)avidin. Two general ways of solving this problem are proposed. One solution takes advantage of the absence of cysteine in the streptavidin sequence: the protein to be purified is selectively readsorbed to thiopropyl-Sepharose through the thiol function generated on DTT cleavage of the biotinylated reagent. The other solution is an empirical approach to make possible the use of avidin, which possesses cysteine residues: combined avidin-Sepharose and thiopropyl-Sepharose chromatography proved efficient when carried out in the presence of urea as denaturing agent.     

Pyrenebutanoate as a dynamic protein modifier for fluorometric detection in capillary zone electrophoresis

Pyrenebutanoate as the amphiphilic fluorescent compound is suggested as a buffer additive in capillary zone electrophoresis (CZE) for a dynamic modification of several protein samples. Using deuterium lamp UV excitation for the on-column fluorometric detection, minimum detectable amounts in the amol-range of the proteins sampled on the CZE capillary was achieved.     

Studies in cyclocopolymerization. III. Copolymerization of divinyl ether with certain nitrogen-containing alkenes

The copolymerization of divinyl ether with fumaronitrile (A), tetracyanoethylene (B), and 4-vinylpyridine (C) has been studied, azobisisobutyronitrile being used as initiator. The compositions of the copolymers were calculated from their nitrogen and unsaturation content. Over a wide range of initial monomer composition, the mole fraction of A in the copolymers lies in the range 0.55–0.63, and the copolymers contained only 2–3% unsaturation, indicating a high degree of cyclization. The composition of the copolymers of B indicated that cyclization occurred to only a small extent, as the copolymers contained rather high unsaturation content. The values of r₁ = 0.23 and r₂ = 0.12 were obtained. The mole fraction of C in the copolymers lies between 0.85 and 0.998. If the assumption is made that r₁ ? r_c ? 0 and there is predominant cyclization, r₂ = 32.0 in this case. The difference in the composition of the copolymers is attributed to the difference between the electron density of the double bonds in A, B, and C.     

Synthesis and functional properties of strongly luminescent diphenylamino end-capped oligophenylenes

Two novel homologous series of oligophenylenes (OPPs) symmetrically end-capped with diphenylamino groups and asymmetrically end-capped with anthryldiphenylamino groups were successfully synthesized by a convergent approach with use of palladium-catalyzed homo- and cross-coupling of arylboronic acids. The absorption maxima of both diphenylamino end-capped OPP series do not vary with the chain length although the molar absorptivities increase sequentially. On the other hand, the emission maxima slightly shift to longer wavelengths when the phenylene unit increases in the series. All the diphenylamino end-capped oligomers exhibit very large fluorescence quantum yields (81-89%). They also exhibit low first ionization potentials, corresponding to the oxidation of the triarylamino moiety, which are essentially unaffected by the oligomeric length extension. The good thermal stabilities of these oligomers allowed the fabrication of multilayer light-emitting devices and their investigations.