Formal syntheses of naturally occurring welwitindolinones

The formal syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone C isonitrile, N-methylwelwitindolinone D isonitrile, 3-hydroxy-N-methylwelwitindolinone C isothiocyanate, and 3-hydroxy-N-methylwelwitindolinone C isonitrile are reported. The synthesis features several novel processes, including a Lewis acid mediated coupling between a benzylic-type heteroaromatic alcohol and a highly functionalized silyl ketene acetal, an intramolecular enolate arylation, and a regioselective, Pd(0)-catalyzed π-allylic cyclization of a γ-benzoyloxy enone moiety that is revealed by unmasking a furan ring.     

Characterizing colloidal behavior of non-ionic emulsifiers in non-polar solvents using electrical impedance spectroscopy

Colloidal behavior of a widely used non-ionic emulsifier, sorbitan monooleate (Span80), was investigated in non-polar solvents (cyclohexane and xylene) using electrical impedance spectroscopy (EIS). The electrical characteristics of the colloidal mixtures were measured with frequency scans ranging from 1 Hz to 200 kHz. The conductances at low frequencies were found to increase with an increase in Span80 concentration. The source of conductivity for non-polar solvents using non-ionic emulsifiers is usually attributed to ionic impurities either in the Span80 or in the non-polar solvents. The measured electrical characteristics for pure Span80 and pure non-polar solvents revealed that the source of ionic conduction is impurities in Span80. It was confirmed that the ionic impurities in the non-polar solvents are in form of aggregate of ions, ion-pairs, and triple ions which is unaffected with the emulsifier concentration. Analyses using equivalent electrical circuits confirmed that the critical Maxwell-Wagner frequency is 0.6–1.8 Hz for the mixtures. The conductance-concentration profiles for the mixtures at 1 Hz showed transitions from a square root to a linear concentration dependence at the CMC. This indicated that the dissociation model holds below the CMC, while the fluctuation model applies above the CMC. The conductance profiles enabled estimates of the relative hydrophilic core radius and the fraction of charged micelles in both non-polar solvents. Figure

CMC determination of non-ionic emulsifier in non-polar solvents     

Chiral HPLC Method for the Novel Triazole Antitubercular Compound MSDRT 12

Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centres. Evaluation of the enantio-specific antitubercular activity has established that the stereoisomer 3 of MSDRT12 (Isomer 3) was the most potent isomer with a minimum inhibitory concentration of 0.78 μg/mL. The other stereoisomers show negligible or no activity. A sensitive, simple, specific, precise and accurate chiral chromatographic method for the direct analysis of the four stereoisomers of MSDRT 12 and the active Isomer 3 has been developed and validated. The method has also been validated for analysing the stereoisomeric impurities Isomer 1, Isomer 2 and Isomer 4 in the active Isomer 3. The separation of the four stereoisomers of MSDRT 12 was achieved using an immobilized polysaccharide-based column, Chiralpak ID with amylose tris(3-chlorophenylcarbamate) as the chiral selector. The separation was performed using a mixture of n-hexane, isopropyl alcohol, ethanol and diethylamine (60:35:5:0.1 v/v/v/v) at a flow rate of 1 mL/min. The method offers excellent separation of the four stereoisomers with resolution more than 1.5 and tailing factor <1.5. The standard curves were linear over the concentration range 5–500 μg/mL and 0.40–505 μg/mL for MSDRT 12 and Isomer 3, respectively. Excellent linearity in the range 0.4–5 μg/mL was obtained for Isomer 1, Isomer 2 and Isomer 4 and these stereoisomeric impurities could be accurately and precisely quantified at a level of 0.1 % of the active isomer.     

Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products

The formal syntheses of N-methylwelwitindolinone C isothiocyanate (4) and several other welwitindolinones 5–8 were achieved by the independent synthesis of 79. The synthesis featured a Lewis acid-mediated coupling between a heteroaryl carbinol and bis-TMS enol ether, an intramolecular enolate arylation, and an unprecedented intramolecular allylic alkylation of a γ-acyloxyenone.     

Liquid Microjunction Surface Sampling Probe Fluid Dynamics: Characterization and Application of an Analyte Plug Formation Operational Mode

The recently discovered sample plug formation and injection operational mode of a continuous flow, coaxial tube geometry, liquid microjunction surface sampling probe (LMJ-SSP) was further characterized and applied for concentration and mixing of analyte extracted from multiple areas on a surface and for nanoliter-scale chemical reactions of sampled material. A transparent LMJ-SSP was constructed and colored analytes were used so that the surface sampling process, plug formation, and the chemical reactions could be visually monitored at the sampling end of the probe before being analyzed by mass spectrometry of the injected sample plug. Injection plug peak widths were consistent for plug hold times as long as the 8 min maximum attempted (RSD below 1.5%). Furthermore, integrated injection peak signals were not significantly different for the range of hold times investigated. The ability to extract and completely mix individual samples within a fixed volume at the sampling end of the probe was demonstrated and a linear mass spectral response to the number of equivalent analyte spots sampled was observed. Using the color and mass changing chemical reduction of the redox dye 2,6-dichlorophenol-indophenol with ascorbic acid, the ability to sample, concentrate, and efficiently run reactions within the same plug volume within the probe was demonstrated.     

Abraham Model Correlations for Transfer of Neutral Molecules to Tetrahydrofuran and to 1,4-Dioxane,and for Transfer of Ions to Tetrahydrofuran

Data have been compiled from the published literature for the partition coefficients of solutes and vapors into anhydrous tetrahydrofuran and 1,4-dioxane. The logarithms of the water-to-ether partition coefficients, log₁₀ P, and gas-to-ether partition coefficients, log₁₀ K, were correlated with the Abraham solvation parameter model. The derived correlations described the observed log₁₀ P and log₁₀ K values for both ether solvents to within average standard deviations of 0.16 log₁₀ units or less. The log₁₀ P correlation for tetrahydrofuran was extended to include the partition of ions by inclusion of a cation-solvent and an anion-solvent term.     

Comprehensive two-dimensional gas chromatography for the analysis of synthetic and crude-derived jet fuels

Fully synthetic jet fuel (FSJF) produced via Fischer-Tropsch (FT) technology was recently approved by the international aviation fuel authorities. To receive approval, comparison of FSJF and crude-derived fuel and blends on their qualitative and quantitative hydrocarbon composition was of utmost importance. This was performed by comprehensive two-dimensional gas chromatography (GC×GC) in the reversed phase mode. The hydrocarbon composition of synthetic and crude-derived jet fuels is very similar and all compounds detected in the synthetic product are also present in crude-derived fuels. Quantitatively, the synthetic fuel consists of a higher degree of aliphatic branching with less than half the aromatic content of the crude-derived fuel. GC×GC analyses also indicated the presence of trace levels of hetero-atomic impurities in the crude-derived product that were absent in the synthetic product. While clay-treatment removed some of the impurities and improved the fuel stability, the crude-derived product still contained traces of cyclic and aromatic S-containing compounds afterwards. Lower level of aromatics and the absence of sulphur are some of the factors that contribute to the better fuel stability and environmental properties of the synthetic fuel. GC×GC was further applied for the analysis of products during Jet Fuel Thermal Oxidation Testing (JFTOT), which measures deposit formation of a fuel under simulated engine conditions. JFTOT showed the synthetic fuel to be much more stable than the crude-derived fuel.     

Liquid Microjunction Surface Sampling Probe Fluid Dynamics: Computational and Experimental Analysis of Coaxial Intercapillary Positioning Effects on Sample Manipulation

A coaxial geometry liquid microjunction surface sampling probe (LMJ-SSP) enables direct extraction of analytes from surfaces for subsequent analysis by techniques like mass spectrometry. Solution dynamics at the probe-to-sample surface interface in the LMJ-SSP has been suspected to influence sampling efficiency and dispersion but has not been rigorously investigated. The effect on flow dynamics and analyte transport to the mass spectrometer caused by coaxial retraction of the inner and outer capillaries from each other and the surface during sampling with a LMJ-SSP was investigated using computational fluid dynamics and experimentation. A transparent LMJ-SSP was constructed to provide the means for visual observation of the dynamics of the surface sampling process. Visual observation, computational fluid dynamics (CFD) analysis, and experimental results revealed that inner capillary axial retraction from the flush position relative to the outer capillary transitioned the probe from a continuous sampling and injection mode through an intermediate regime to sample plug formation mode caused by eddy currents at the sampling end of the probe. The potential for analytical implementation of these newly discovered probe operational modes is discussed.     

Study of Interaction of Silver Nanoparticles with Bovine Serum Albumin Using Fluorescence Spectroscopy

The interaction between silver nanoparticles (SNPs) and Bovine Serum Albumin (BSA) was investigated at physiological pH in an aqueous solution using fluorescence spectroscopy. The analysis of fluorescence spectrum and fluorescence intensity indicates that SNPs have a strong ability to quench the intrinsic fluorescence of BSA by both static and dynamic quenching mechanisms. Resonance light scattering (RLS) spectra indicated the formation of a complex between BSA and SNP. The number of binding sites ‘n’ and binding constants ‘K’ were determined at different temperatures based on fluorescence quenching. The thermodynamic parameters namely ∆H^°, ∆G^°, ∆S^° were calculated at different temperatures and the results indicate that hydrophobic forces are predominant in the SNP-BSA complex. Negative ∆G^° values imply that the binding process is spontaneous. Synchronous fluorescence spectra showed a blue shift which is indicative of increasing hydrophobicity.     

Study of dipole dynamics and pre-transitional effects at isotropic to nematic phase transition by low-frequency dielectric relaxation measurements

Thermal microscopy (TM) as well as low-frequency (LF) dielectric relaxation studies are carried out on a nematic liquid crystal (NLC), viz E7 (Merck Ltd, UK). The isotropic to nematic (IN) transition temperatureT _IN determined by TM and LF-dielectric permittivity measurements agrees with the available data. Dielectric loss studies in the frequency region of 5–10?MHz indicate a relaxation (in the kHz region) akin to Debye type off-centered dispersion. The observed nematic relaxation is found to correspond to reorientation (about the short axis) of the nematic dipole to the external field. The temperature variation of the nematic relaxation frequencyf _R is found to follow an Arrhenius shift, with an activation energy of 1.7?eV. Temperature variation of the dielectric strength (Δε = ε _o ? ε_∞) and the distribution parameter α in the nematic phase are discussed. The dynamic response of the nematic dipoles and growth of pre-transitional fluctuations are found to be nonlinear in the vicinity of the IN transition. The value of the exponent α_eff = 0.072 indicates weak growth of transitional fluctuations across the IN transition.