Parallel and multiplexed bead-based assays and encoding strategies

Advances in high throughput screening (HTS), together with the rapid progress in combinatorial chemistry, genomic and proteomic sciences have dramatically stimulated the development of a variety tools to enable the drug discovery process to become more efficient. Major future challenges in HTS include obtaining high density and good quality data based on assays that are rapid, reliable, inexpensive, sensitive, simple and miniaturised. This paper reviews the development and role of bead-based assays for HTS including DNA and single nucleotide polymorphism (SNP) assays, particularly from a multiplex perspective and evaluating the recent advances in bead-based arrays. The encoding strategies that are commonly used in bead-based assays are highlighted, while the importance of magnetic beads in genomic and proteomic purifications is discussed. In conclusion, bead-based assays offer a powerful promising approach for many aspects of drug discovery.     

Synthesis of (-)-Vulcanolide by enantioselective protonation

Two efficient enantioselective syntheses of the more active (S,S)-enantiomer of the powerful musk odorant Vulcanolide are described. In both syntheses, the key step is an enantioselective protonation of a ketone enolate. A third enantioselective protonation, of a thiol ester enolate, was applied for the determination of the absolute configuration of Vulcanolide by comparison with a known compound.     

Detection of soil pollution by hydrocarbons using headspace-mass spectrometry and identification of compounds by headspace-fast gas chromatography-mass spectrometry

The direct coupling of a headspace sampler with a mass spectrometer is proposed as a screening tool for the rapid detection of soil pollution by hydrocarbons from petroleum and derivatives. The samples are subjected to the headspace generation process, with no prior treatment, and the volatiles generated are introduced directly into the mass spectrometer, thereby obtaining a fingerprint of the sample analysed. Suitable treatment of the signal by chemometric techniques allows unequivocal characterisation of the different types of sample. The use of fast gas chromatography with a mass spectrometer detector coupled to the headspace sampler allows identification of the major hydrocarbons present in the mineral and organic polluted samples, interpretation of the results obtained, and demonstrates the analytical potential of headspace-mass spectrometry coupling.     

Spectroscopic investigation of the adsorption and oxidation of thiourea on polycrystalline Au and Au(111) in acidic media

In the present paper, a systematic electrochemical investigation on thiourea (TU) electrooxidation was developed on polycrystalline and (111) single-crystal gold electrodes in 0.1 M perchloric acid. The combination of cyclic voltammetry with in situ Fourier transform infrared spectroscopy (FTIRS) and differential electrochemical mass spectrometry techniques have allowed the nature of the species formed during the electroadsorption and electrooxidation of TU to be established. FTIRS experiments were performed in D2O to clean up the region of the H2O bending around 1600 cm(-1). It was concluded that TU adsorbs tilted on the surface in the 0.05-0.40 VRHE potential range. A dual-path reaction mechanism was evidenced in the oxidation process. The first pathway takes place from adsorbed TU at E > 0.40 VRHE and implies the formation of [Au(I)-(TU)2]+, which is oxidized to NH2CN and S0 at E > 0.80 VRHE. In a following oxidation step at E > 1.20 V, N2, CO2, and HSO4-/SO4(2-) were produced. The second parallel reaction occurs from TU in solution at E > 0.50 VRHE to form (TU)2(2+). All these species were characterized from the spectroscopic experiments. Similar results were obtained for both surfaces.     

Extraction of capsaicins in aerosol defense sprays from fabrics

The use of aerosol defense sprays has increased as a means of self-defense and as a weapon in the commission of a crime. The residue of these sprays is often left behind as physical evidence on a victim's clothing or personal belongings. As the popularity of self-defense weaponry increases, so does the likelihood that it will be encountered in forensic casework. The extraction, recovery from fabrics, and identification of residue from defense sprays is described. The commonly used extraction method of liquid-liquid extraction is compared to solid phase microextraction (SPME) to recover capsaicin and dihydrocapsaicin from cotton swabs. The use of SPME resulted in lower limits of detection and greater recovery efficiency when compared to solvent extraction. SPME also provided more consistent recovery and less variability when compared to solvent extraction. The effect of use of various types of evidence packages on the preservation of this type of evidence is also reported. The collection and analysis of hand swabs after normal discharge of pepper spray canisters was studied indicating the low persistence of these compounds on the hands of the person conducting the spraying. Finally, the results of a real case whereby solvent-solvent extraction did not provide the necessary sensitivity for extracting the capsaicin compounds on the garments of a victim of an alleged spraying and the SPME extraction provided the recovery and identification of the compounds is also presented.     

Molecular dynamics simulations of the surface tension of ionic liquids

We report molecular dynamics computer simulations of the surface tension and interfacial thickness of ionic liquid-vapor interfaces modeled with a soft core primitive model potential. We find that the surface tension shows an anomalous oscillatory behavior with interfacial area. This observation is discussed in terms of finite size effects introduced by the periodic boundary conditions employed in computer simulations. Otherwise we show that the thickness of the liquid-vapor interface increases with surface area as predicted by the capillary wave theory. Data on the surface tension of size-asymmetric ionic liquids are reported and compared with experimental data of molten salts. Our data suggest that the surface tensions of size-asymmetric ionic liquids do not follow a corresponding states law.     

Ru-catalyzed oxidation of substituted acetylenes to α-keto esters and α-keto amides with iodosylbenzene

Oxidation of alkynyl ethers and -amines with iodosylbenzene in presence of Ru-catalysts affords α-keto esters and α-keto amides in 44–85% yield. These conversions can also be effected with RuO₄.     

Cascade alkenyl amination/Heck reaction promoted by a bifunctional palladium catalyst: a novel one-pot synthesis of indoles from o-haloanilines and alkenyl halides

A novel approach for the synthesis of the important indole ring is described. Indoles are obtained from o-bromoanilines and alkenyl halides in a Pd-catalyzed cascade process that involves an alkenyl amination followed by an intramolecular Heck reaction. The overall process represents the first example of the participation of alkenyl amination reactions in Pd-catalyzed cascade reactions. Initially, the relative reactivity of aryl and alkenyl bromides and chlorides towards Pd-catalyzed amination was investigated. Competition experiments were carried out in the presence of primary and secondary amines, and these revealed the reactivity order alkenyl bromides > aryl bromides > alkenyl chlorides > aryl chlorides, as well as very high chemoselectivity; the more reactive halide was always favored. Thereafter, optimized reaction conditions for the sequential alkenyl amination/Heck cyclization to give indoles were investigated with the model reaction of o-bromoaniline with alpha-bromostyrene. An extensive screening of ligands, bases, and reaction conditions revealed that the [Pd2(dba)3]/DavePhos, NaOtBu, toluene combination at 100 degrees C were the optimized reaction conditions to carry out the cascade process (dba=dibenzylideneacetone, DavePhos=2-dicyclohexylphosphino-2'-N,N-dimethylaminobiphenyl). The reaction proceeds with aryl, alkyl, and functionalized substitutents in both starting reactants. The cyclization was also studied with N-substituted o-bromoanilines (which would give rise to N-substituted indoles); however, in this case, indole formation occurred only with 1-substituted-2-bromoalkenes. Finally, the application of this methodology to o-chloroanilines required further optimization. Although the catalyst based on DavePhos failed to promote the cascade process, a catalytic combination based on [Pd2(dba)3]/X-Phos promoted the formation of the indole ring also from the less reactive chloroanilines.     

Some remarks on the homogenization of the dam problem

The homogenization of the dam problem is discussed in the general weak formulation by means of the technique of correctors. In the two special cases of horizontal layers and of the isotropic coefficients with separated variables the problem is solved. However, in general, the unsaturated region is not stable for the homogenization, as a counterexample by Alt shows.     

Das Schwingungsspektrum von Barium-Divanadat

The infrared and laser-Raman spectra of crystalline Ba₂V₂O₇ are reported and discussed by means of a Site Symmetry analysis.

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