Determining the scope of the organolanthanide-catalyzed, sequential intramolecular amination/cyclization reaction: formation of substituted quinolizidines, indolizidines, and pyrrolizidines

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction was determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines. A methyl group was installed at diverse positions in the substrates to determine the sense and magnitude of diastereoselection. High diastereoselectivity (>20:1) was achieved for the formation of some quinolizidines and indolizidines. The sense of relative asymmetric induction was contrary to previously studied systems, and although some questions remain, a rationalization for these results is put forward.     

Trace determination of peptides in water samples using packed capillary liquid chromatography with UV and MS detection and characterization of peptide oxidation products by MS

A capillary liquid chromatographic column switching method has been developed for fast and sensitive determination of peptides in water samples. Sample volumes of 1 mL were loaded onto a (320 m I.D. ×30 mm) 10 m Kromasil C₁₈ pre-column, providing on-line analyte enrichment, prior to back-flushed elution onto a (320 m I.D. ×150 mm) 3.5 m Kromasil C₁₈ analytical column. Loading flow rates of 250 L/min and a mobile phase composition of acetonitrile/water/trifluoroacetic acid (22/77.9/0.1, v/v) provided a total analysis time of less than 25 minutes for the test peptides angiotensin II, bombesin, bradykinin, corazonin, neurotensin and substance P, using temperature programmed elution. In addition, solvent gradient elution and combined solvent gradient elution and temperature programming were explored. Using on-capillary UV detection at 210 nm resulted in a concentration limit of detection (cLOD) of about 1 ng/mL. The method was validated over the concentration range 1–100 ng/mL, yielding a coefficient of correlation of 0.997 or better. The within-assay (n=6) and between-assay (n=6) precisions of peak areas were on average 6% RSD and 5% RSD, respectively.When the method was applied to spiked chlorinated tap water samples, it was found that peptides containing methionine, tryptophan and cystine were oxidized. Identification of the oxidation products of the peptides in hypochlorite-treated water was done with positive electrospray ionization time-of-flight mass spectrometric detection.     

Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of potassium aryl- and heteroaryltrifluoroborates

An extended study of the reactivity of potassium aryl- and heteroaryltrifluoroborates in Suzuki-Miyaura cross-coupling reactions is presented. The coupling of aryl- and electron-rich heteroaryltrifluoroborates with aryl and activated heteroaryl bromides proceeds readily under ligandless conditions. When deactivated aryl- and heteroaryltrifluoroborates are coupled with aryl and heteroaryl bromides and chlorides, a low loading (0.5-2%) of PdCl(2)(dppf).CH(2)Cl(2) efficiently catalyzes the reactions. Under either condition, reactions can generally be carried out in an open atmosphere.     

Temperature-promoted large-volume solute enrichment in column-switching miniaturized liquid chromatography: determination of an antioxidant

A two-valve sub-ambient temperature-promoted reversed-phase packed-capillary liquid-chromatography column-switching system has been tailored for sensitive determination of hydrophobic compounds. Such compounds are not easily dissolved in solvent mixtures of non-eluting properties that traditionally are used for solute enrichment in reversed-phase liquid chromatography. Enrichment-column solute focusing of large sample volumes was promoted by use of sub-ambient temperatures only, allowing the use of sample solvents that were stronger or equal to the mobile phase solvent strength. Subsequent column switching and enrichment-column temperature increment provided efficient low-dispersion back-flushed enrichment-column solute desorption onto the analytical column, where the solute was subjected to temperature-programmed gradient action. The antioxidant, Irganox 1076 (octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) extracted from low density polyethylene with 100% acetonitrile served as a hydrophobic model compound. The mobile phase consisted of acetonitrile containing 10 mM triethylamine and formic acid, and the 0.25 mm id enrichment-column and analytical column in lengths of 27 and 250 mm, respectively, were packed with 3.5 microm Kromasil C18 particles. Sample volumes of up to 500 microL were successfully focused on the enrichment column at 5 degrees C using loading flow rates of up to 40 microL min(-1) prior to temperature programming to 90 degrees C. The concentration limit of detection of Irganox 1076 was 6 ng mL(-1) when using an injection volume of 500 microL. The within-assay precision was in the range 3.5-6.8% (n = 6) while the between-day precision was 7.5% (n = 3) relative standard deviation. The method was linear within the investigated mass range 3-100 ng (R2 = 0.9993).     

The impact of column inner diameter on chromatographic performance in temperature gradient liquid chromatography

The impact of column inner diameter on chromatographic performance in temperature gradient liquid chromatography has been investigated in the present study. Columns with inner diameters of 0.32, 0.53, 3.2 and 4.6 mm were compared with respect to retention and efficiency characteristics using temperature gradients from 30 to 90 degrees C with temperature ramps of 1, 5, 10 and 20 degrees C min(-1). The columns were all of 15 cm length and were packed with 3 microm Hypersil ODS particles. Alkylbenzenes served as model compounds, and the mobile phase consisted of acetonitrile-water (50:50, v/v). The study revealed that the column ID is not a critical limiting factor when performing temperature programming in LC, at least for columns narrower than 4.6 mm inner diameter in the temperature interval 30-90 degrees C. The retention times for all components on all columns were highly comparable, with similar peak profiles without any signs of peak splitting. The use of mobile phase pre-heating when using the larger bore columns was avoided by starting the temperature gradients close to ambient. However, the relative apparent efficiency was inversely proportional to column inner diameter, making the capillary columns generally more functional towards temperature gradients than the larger bore columns with respect to chromatographic efficiency. In addition, the capillary columns possessed higher robustness towards temperature programming than the conventional columns.     

Temperature‐Programmed Packed Capillary Liquid Chromatography Coupled to Fourier‐Transform Infrared Spectroscopy

Temperature‐programmed packed capillary liquid chromatography has been coupled off‐line to Fourier‐transform infrared spectroscopy, utilizing a commercially available interface with a pneumatic nebulizer rebuilt to handle low flow rates at elevated temperatures. The modified interface showed excellent performance with regard to non‐aqueous reversed phase separations of polymer additives, resulting in constructed Gram‐Schmidt chromatograms comparable to chromatograms obtained using UV detection. The spray of the in‐house constructed nebulizer was not influenced by temperature changes of the column effluent, and hence temperature‐programmed gradient separations could be used successfully. The relative standard deviation of peak height was 4.4% (n = 5) and the mass limit of detection was determined to be about 40 ng, using a polymer antioxidant as model compound. The present instrumental coupling has been used for characterization of the antioxidant Irgafos P‐EPQ.     

Numerical analysis of the rotational relaxation time of spectrin segments and spectrin heterodimer in dilute aqueous solution

The rotational relaxation time for different models of the spectrin αβ-heterodimer and spectrin subunits were obtained through numerical simulation making use of the so-called rigid-body approximation. Based on information on the helix structure of the 106 aminoacids in the repeating motif of spectrin, three different models with varying degree of refinement were set up to represent the spectrin subunits: the two-bead, the many-bead and the shell model. For one- and two-subunit spectrin the relaxation time was found to be 20 ± 4 ns and 92 ± 5 ns, respectively. The last result conforms well with available experimental data from transient electric birefringence measurements. For the αβ-heterodimer two different models were applied: a chain of beads (pearl necklace model) and a more refined so-called San necklace model. Using the San necklace model, the relaxation time was found to be in the range of 9 to 18 μs (depending on the flexibility of the joint), which is in accordance with what has been obtained from intrinsic viscosity measurements, but considerably higher than experimental data from measurements of transient electric birefringence.