Control of skeletal connectivity in indium promoted reactions: 1,2-additions and cope rearrangements en route to lactol formation

Indium promoted coupling reactions between propargyl aldehydes (3) and allyl halides under aqueous and organic conditions are reported. Coupling reactions under aqueous conditions occur via 1,2-addition with excellent yields to afford 4-hydroxy-1-ene-5-ynes (8). Coupling reactions under organic conditions also add in a 1,2-fashion, but the initial products can be induced to undergo oxy-Cope rearrangements giving 2,5-hexadienals (9). Oxy-Cope rearrangement of 8 followed by a secondary addition step under highly basic conditions leads to lactol formation (10) in good to excellent yields. This paper reveals the versatility and control of product formation which may be attained when working with propargyl aldehyde (3) and allyl halide systems under indium promoted coupling conditions.     

Probing electronic communication in stable benzene-bridged verdazyl diradicals

Two benzene-bridged N,N'-bis(isopropyl)6-oxoverdazyl diradicals 7a (1,4-benzene-bridged) and 7b (1,3-benzene-bridged) were prepared and studied by an array of physicochemical techniques aimed at elucidating the intramolecular electronic and magnetic coupling between verdazyl chromophores. The very high stability of these diradicals permits comprehensive investigations of their properties for the first time. The UV-vis spectra suggest negligible direct conjugative overlap involving the radical SOMOs, although significant differences in higher energy absorptions suggest that radical orbitals other than the SOMO are likely communicating via the central p-phenylene bridge in 7a. The electrochemical features of the two diradicals are nearly identical; in each derivative, both radicals are oxidized essentially independently while the reductions occur in a stepwise manner with differences of approximately 100 mV between the two reductions. EPR and magnetic susceptibility collectively indicate that the para-bridged diradical is weakly antiferromagnetically coupled while the meta analogue is weakly ferromagnetically coupled, in accord with the topology of the substitution pattern on the central benzene ring.     

Two-chiral-component microemulsion electrokinetic chromatography-chiral surfactant and chiral oil: part 1. dibutyl tartrate

The first simultaneous use of a chiral surfactant and a chiral oil for microemulsion EKC (MEEKC) is reported. Six stereochemical combinations of dodecoxycarbonylvaline (DDCV: R, S, or racemic, 2.00% w/v), racemic 2-hexanol (1.65% v/v), and dibutyl tartrate (D, L, or racemic, 1.23% v/v) were examined as chiral pseudostationary phases (PSPs) for the separation of six pairs of pharmaceutical enantiomers: pseudoephedrine, ephedrine, N-methyl ephedrine, metoprolol, synephrine, and atenolol. Subtle differences were observed for three chromatographic figures of merit (alpha(enant), alpha(meth), k) among the chiral microemulsions; a moderate difference was observed for efficiency (N) and elution range. Dual-chirality microemulsions provided both the largest and smallest enantioselectivities, due to small positive and negative synergies between the chiral microemulsion components. For the ephedrine family of compounds, dual-chiral microemulsions with surfactant and oil in opposite stereochemical configurations provided higher enantioselectivities than the single-chiral component microemulsion (RXX), whereas dual-chiral microemulsions with surfactant and oil in the same stereochemical configurations provided lower enantioselectivities than RXX. Slight to moderate enantioselective synergies were confirmed using a thermodynamic model. Efficiencies observed with microemulsions comprised of racemic dibutyl tartrate or dibutyl-D-tartrate were significantly higher than those obtained with dibutyl-L-tartrate, with an average difference in plate count of about 25 000. Finally, one two-chiral-component microemulsion (RXS) provided significantly better resolution than the remaining one- and two-chiral-component microemulsions for the ephedrine-based compounds, but only slightly better or equivalent resolution for non-ephedrine compounds.     

Influence of microemulsion chirality on chromatographic figures of merit in EKC: results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions

Novel microemulsion formulations containing all chiral components are described for the enantioseparation of six pairs of pharmaceutical enantiomers (atenolol, ephedrine, metoprolol, N-methyl ephedrine, pseudoephedrine, and synephrine). The chiral surfactant dodecoxycarbonylvaline (DDCV, R- and S-), the chiral cosurfactant S-2-hexanol, and the chiral oil diethyl tartrate (R- and S-) were combined to create four different chiral microemulsions, three of which were stable. Results obtained for enantioselectivity, efficiency, and resolution were compared for the triple-chirality systems and the single-chirality system that contained chiral surfactant only. Improvements in enantioselectivity and resolution were achieved by simultaneously incorporating three chiral components into the aggregate. The one-chiral-component microemulsion provided better efficiencies. Enantioselective synergies were identified for the three-chiral-component nanodroplets using a thermodynamic model. Additionally, two types of dual-chirality systems, chiral surfactant/chiral cosurfactant and chiral surfactant/chiral oil, were examined in terms of chromatographic figures of merit, with the former providing much better resolution. The two varieties of two-chiral-component microemulsions gave similar values for enantioselectivity and efficiency. Lastly, the microemulsion formulations were divided into categories based on the number of chiral microemulsion reagents and the average results for each pair of enantiomers were analyzed for trends. In general, enantioselectivity and resolution were enhanced while efficiency was decreased as more chiral components were used to create the pseudostationary phase (PSP).     

Synthesis of the docosanasaccharide arabinan domain of mycobacterial arabinogalactan and a proposed octadecasaccharide biosynthetic precursor

Two major components of the cell wall in mycobacteria, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), are polysaccharides containing arabinofuranose residues. In one of these polysaccharides, arabinogalactan, this arabinan domain consists of three identical motifs of 22 arabinofuranose residues, which are in turn attached to an underlying galactofuranan backbone. Recent studies have proposed that this docosanasaccharide motif, and a structurally related arabinan present in another cell wall polysaccharide, lipoarabinomannan, are biosynthesized from a common octadecasaccharide precursor. To facilitate the testing of this hypothesis, we report here the first total syntheses of these 18- and 22-residue oligosaccharides both functionalized with an aminooctyl linker arm. The route to the target compounds involved the preparation of four tri- to heptasaccharide building blocks possessing only benzoyl protecting groups that were coupled in a highly convergent manner via glycosyl trichloroacetimidate donors. Each of the targets could be prepared in only six steps from these intermediates, and in both cases more than 10 mg of material was obtained. These compounds are expected to be useful tools in probing the biosynthesis of these arabinan-containing polysaccharides. Such studies are essential prerequisites for the identification of novel anti-TB agents that target arabinan assembly.     

Optical artefacts in transflection mode FTIR microspectroscopic images of single cells on a biological support: the effect of back-scattering into collection optics

Infrared microspectroscopic imaging data of single human prostate cancer cells, on an artificial extracellular matrix (Matrigel) thin-film surface, are presented. The spectral intensity maps, obtained in reflection mode, appear to show that the protein intensity distribution observed at the location of a cell changes dramatically depending on the concentration and/or thickness of the underlying Matrigel layer. Specifically, cells adhered to a low protein concentration or thin surface exhibit a higher protein intensity signal than the surrounding layer whereas those on a high protein concentration or thick surface exhibit a lower protein intensity signal. These results are qualitatively explained by a simple model that takes into account the fact that radiation scattered from cells can enter the collection optics of the microscope without passing through the Matrigel layer. This leads to an apparent reduction in absorption at the cell.     

Nonlinear signal mixing in a three-terminal molecular wire

The authors study the electronic response of two simple molecular devices to a bichromatic field, where the device acts as a mixer. Two closely related model systems are considered: one is a benzene molecule and the other is a single grapheme sheet, and in both cases the systems are connected to three polyacetylene chains. The electronic response to the dichromatic alternating electric fields is studied by following the electron density fluctuation along the chain lengths. In both cases the electron transfer follows the field frequency at low electric fields. At higher amplitude, a significant amount of nonlinear mixing resulting in new combinations of the input frequencies is found in the spectrum. The influence of gating on the output frequencies is also shown.     

Convenient and rapid determination of cimetidine in human plasma using perchloric acid-mediated plasma protein precipitation and high-performance liquid chromatography

This study demonstrates the analysis of cimetidine in human plasma with HPLC using a simplified sample preparation by protein precipitation with perchloric acid. Plasma cimetidine concentration was determined by plotting peak height ratio of cimetidine to ranitidine (internal standard, IS) against cimetidine concentrations in plasma. The cimetidine and ranitidine peaks were completely separated and no interference from plasma was observed. The lower limit of quantification (LLOQ) of the method was established at 0.1 microg/mL with a precision of 4.3% and a relative error of 1.9%. The average analytical recovery was >90% over the range of cimetidine concentrations (0.1-15.0 microg/mL). The linearity of calibration curve was excellent (r(2) > 0.999). The within- and between-day precision and accuracy, expressed as the coefficients of variation and relative error, were found to be less than 5%. Compared with previously reported methods, the analytical technique for cimetidine determination in human plasma presented here demonstrates comparable accuracy and precision, an acceptable analysis time, shorter and simpler sample preparation, and a reduced need for complicated equipment. The method presented here is simple and rapid, and the precision and sensitivity are appropriate for the determination of cimetidine in plasma in pharmacokinetic studies.     

Effects of pulsed ultrasound on the adsorption of n-alkyl anionic surfactants at the gas/solution interface of cavitation bubbles

Sonolysis of argon-saturated aqueous solutions of the nonvolatile surfactants sodium dodecyl sulfate (SDS) and sodium 1-pentanesulfonate (SPSo) was investigated at three ultrasonic frequencies under both continuous wave (CW) and pulsed ultrasound. Secondary carbon-centered radicals were detected by spin trapping using 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS) and electron paramagnetic resonance (EPR) spectroscopy. Following sonolysis, -*CH- radicals were observed for both surfactants under both sonication modes. Under CW at 354 kHz, the maximum plateau -*CH- radical yield was higher for SPSo than for SDS, indicating that SDS, which is more surface active under equilibrium conditions, accumulates at the gas/solution interface of cavitation bubbles to a lesser degree, compared with the less surface active surfactant, SPSo. However, after sonolysis (354 kHz) under pulsed ultrasound with a pulse length of 100 ms and an interval of 500 ms, the -*CH- radical yield at the plateau concentrations was higher for SDS than for SPSo due to increased amounts of SDS accumulation on the bubble surfaces. In contrast to the findings following sonolysis at 354 kHz, sonolysis of aqueous surfactant solutions at 620 kHz and 803 kHz showed a higher -*CH- radical yield for SDS compared with SPSo under CW but lower -*CH- radical yield with increasing pulsing interval, indicating a frequency dependence on accumulation. Results indicate that pulsing the ultrasonic wave has a significant effect on the relative adsorption ability of n-alkyl surfactants at the gas/solution surface of cavitation bubbles.     

Electrochemical deposition of poly(trans-[RuCl2(4-vinylpyridine)4]) and its reductive desorption: cyclic voltammetry and electrochemical quartz crystal microbalance studies

The electropolymerization of trans-[RuCl(2)(vpy)(4)](vpy = 4-vinylpyridine) on Au or Pt electrodes was studied by cyclic voltammetry and the electrochemical quartz crystal microbalance (EQCM) technique. Cyclic voltammetry of the monomer in DMSO on Au shows reductions at -2.0 and -2.2 V. Potential cycling over the first wave leads to polymer formation; however, scanning over the second wave leads to desorption of the polymer. These observations were confirmed by EQCM measurements which also revealed a high polymerization efficiency. Electrolysis, EQCM and XPS measurements showed that desorption was associated with substitution of chloride ligands by DMSO when the polymer was in a highly reduced state. The film also showed reversible mass changes due to the oxidation and accompanying ingress of charge-balancing anions and solvent into the film. Measurements on the dried films revealed that large quantities of solvent are trapped in the film during the electropolymerization process.