The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes using pyrrolidine as an organocatalyst

The first catalytic inverse-electron demand hetero-Diels-Alder reaction of nitroso alkenes has been developed. Nitroso alkenes were generated in situ from alpha-halooximes and underwent [4 + 2]-cycloadditions with enamines as dienophiles formed from aldehydes and pyrrolidine (10 mol%) as an organocatalyst. The presence of a suitable heterogeneous buffer system was found to be essential and best results were obtained with sodium acetate trihydrate. The resulting 5,6-dihydro-4H-oxazines were obtained in moderate to good yields under mild reaction conditions. A catalytic cycle has been proposed and evidence for the cycloaddition mechanism has been obtained. Moderate asymmetric induction (42% ee) was observed when a chiral secondary amine was used.     

Pre-equilibrium capillary zone electrophoresis or frontal analysis: advantages of plateau peak conditions in affinity capillary electrophoresis

The feasibility of using the affinity CE methodologies pre-equilibrium CZE and CE frontal analysis was tested on interaction systems exhibiting rapid on-and-off kinetics. Experimentally, the methodologies differ only with respect to the volume of sample introduced into the capillary. Pre-equilibrium CZE has been considered amendable to interactions with slow on-and-off kinetics only; however, it has recently been applied in studies of interactions with fast on-and-off kinetics. The effect of varying the sample volume introduced hydrodynamically into the capillary on the apparent degree of complexation was studied. For two different binding systems, the fraction of free analyte was found to be overestimated using pre-equilibrium CZE as compared to volumes providing plateau peak conditions as used with frontal analysis. Results indicate that frontal analysis conditions lead to more robust binding assays and thus more reliable data. The validity of data obtained by pre-equilibrium CZE may be low, thus the use of an experimental setup providing plateau peaks is highly recommended. It is suggested that the effect of altering the sample volume on the degree of binding should be investigated as part of method development and validation.     

Determination of octanol-water partition coefficients for carbonate esters and other small organic molecules by microemulsion electrokinetic chromatography

Microemulsion electrokinetic chromatography (MEEKC) was assessed as a tool for determination of octanol-water partition coefficients using 34 solutes encompassing 8 carbonate esters. It was confirmed that microemulsions containing 1.44-2.88% w/w SDS, 6.49% w/w 1-butanol, and 0.82% w/w n-heptane constitute a good model of octanol-water partitioning in the pH range of 1.4-7.4. Use of the migration index concept led to improved repeatability of the MEEKC method compared to the use of retention factors. Using a dynamical coating, a high electroosmotic flow at pH 1.4 and 4.75 was achieved expanding the practical pH working range of the MEEKC system. The correlation obtained between the migration index and log P was unaffected by pH indicating that the properties of the microemulsion droplets and, thus, partitioning are independent of pH. No evidence for congeneric behavior was found for the sample set comprising solutes with different hydrogen bonding properties suggesting that simple reference compounds can be used as calibrators. Lipophilicity estimates for the series of carbonate esters were obtained. The increase in lipophilicity with chain length was smaller than expected from the Hansch substituent constant, pi.     

Synthesis and crystal structure of ammonium (picrate) (dibenzo-18-crown-6)

NH₄(Pic)(DB18C6) (Pic=picrate and DB18C6=dibenzo-18-crown-6), (C₂₆H₃₀N₄O₁₃) FW 606.56, arthorhombic,Pmn2₁,a=26.045(5),b=12.055(3),c=8.982(3) Å,V=2820(1) ų,Z=4,D _c =1.429 g/cm³, CuK, =1.54184 Å, (CuK)=9.5 cm^–1,F(000)=1272,T=298 K. The structure has been refined toR=0.0475 for 2617 unique observed reflections. In the lattice the 1:1 complex exists as a 2:2 dimer in which the crown are coupled through the Pic anions and NH₄ ⁺ cations. The asymmetric unit consists of two independent half crown ethers of which two opposite O atoms are on the mirror plane, two half ammonium cations of which the N and two H atoms are also on the mirror plane while the Pic anion is in a general position. Relative to each other, the corwn ethers are shifted by about 7.3 Å alongb and 1 Å alongc. The 1:1 sandwich of NH₄ with DB18C6 and Pic on dimerisation becomes a club pseudo-sandwich with three phenyl rings on either side of the mirror plane, thus forming a nearly parallel stack with a 3.6 Å inter-ring distance. The NH₄ ions hold the structure; two H atoms on the mirror plane are hydrogen-bonded to the opposite oxygens of the crown located on the purely aliphatic part of the ring (2.10(1), 2.06(3) and 2.26(3), 2.05(1) Å) for the two independent crowns, respectively, while the other two H atoms form mirror-related bifurcated hydrogen bonds with the phenoxide oxygen (1.99(1) and 2.01(1) Å) and theo-nitrogen oxygen (2.44(2) and 2.34(1) Å) of the picrates. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82037 (29 pages)     

Potential of short-column liquid chromatography with tandem mass spectrometric detection for the rapid study of pesticide degradation

Summary The applicability of solid-phase extraction-LC using two short columns (SPE-LC) and/or single-short-column liquid chromatography (SSC) combined on-line with tandem mass spectrometry (MS) was demonstrated for the rapid study of pesticide degradation. A fast analytical procedure was developed to provide preliminary information concerning experimental conditions, approximate rates of degradation and identity of the degradation products. Surface water samples were spiked at relevant concentration levels with well-known microcontaminants and photolysis was used to transform parent compounds into their degradation products. In general, the strategy was as follows: at 30-min intervals 10-mL samples were on-line enriched, separated by short-column LC and recorded in full-scan MS to obtain information on the disappearance of the parent compound and the appearance of breakdown products. To obtain structural information, product-ion spectra of selected compounds appearing in the full-scan MS chromatogram were recorded; this enabled the identification of several degradation products. Total analysis time of enrichment/separation and detection was about 10–15 min.     

Methylene radical cation transfer from ionized oxirane to CH3SCH3 and C6H5SCH3 in the gas phase: Formation of sulphur distonic ions and/or insertion in a carbon–sulphur bond

The α-distonic sulphur-containing ion $ {}^ \cdot {\rm CH}_2 \mathop {\rm S}\limits^ + \left({{\rm CH}_3 } \right)_2 $ has been generated by transfer of CH from ionized oxirane to dimethyl thioether and distinguished from the molecular ion of ethyl methyl thioether by collision induced dissociation (CID) experiments. In particular, the α-distonic ion expels CH₂ to a minor extent following collision, whereas the molecular ion of ethyl methyl thioether does not undergo this reaction. The metastable C₃H₈S^+˙ ions formed by CH transfer to dimethyl thioether and ionization of ethyl methyl thioether decompose by competing losses of CH₃R˙, CH₄ and C₂H₄. The elimination of ethene is taken as evidence for isomerization of the α-distonic ion to the molecular ion of ethyl methyl thioether prior to spontaneous dissociation. Evidence for the formation of stable α-distonic sulphur-containing ions by transfer of CH from ionized oxirane to methyl phenyl thioether has not been obtained. The collision-induced and spontaneous reactions of the ions formed by CH transfer to methyl phenyl thioether indicate that a mixture of the radical cations of CH₃C₆H₄SCH₃, C₆H₅SCH₂CH₃ and C₆H₅CH₂SCH₃ is generated implying that attack on the phenyl group occurs in addition to a formal insertion of a methylene entity in a C? S bond.     

Combination of LC-ICP-MS, LC-MS and NMR for investigation of the oxidative degradation of selenomethionine

Selenomethionine (SeMet) was oxidized by heating an acidic solution with hydrogen peroxide. Samples were taken before and during the oxidation process. The oxidation products were separated by cation exchange chromatography followed by ICP-MS detection to identify the selenium containing compounds as well as electrospray ionization MS detection to determine the masses of the degradation products. Furthermore, the samples were analyzed by ⁷⁷Se-NMR. The first appearing degradation product was selenomethionine selenoxide, which was converted via the deaminated selenoxide to methane seleninic acid and selenite.     

Energy-dependent reversal of secondary isotope effects on simple cleavage reactions: Tertiary amine radical cations with deuterium at remote positions

Deuterium substitution at remote sites gives rise to inverse secondary kinetic isotope effects on the α-cleavage of a number of tertiary amines in the ion source, but to normal isotope effects on reactions occurring in the field-free regions. The change from normal to inverse secondary isotope effects when the internal energy of the reacting ions increases is consistent with transition-state models that involve slight lowering of vibrational frequencies also for bonds well removed from the site of cleavage. The isotope effect on the reactions of ions of high internal energy is caused by the influence that even small changes of isotope-dependent frequencies have on the state sums (a statistical weight effect favouring loss of the labelled radical), whereas the behaviour of low-energy ions is determined by the zero-point energy changes which favour loss of the unlabelled fragment.     

DISTRIBUTION OF 5-AMINOLEVULINIC ACID-INDUCED PORPHYRINS IN NODULOULCERATIVE BASAL CELL CARCINOMA

Abstract— Microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced porphyrins in 22 patients with a total number of 52 noduloul-cerative basal cell carcinomas (BCC) after topical ALA application with or without dimethylsulfoxide (DMSO)/ethylenediaminetetraacetic acid (EDTA) or after intravenous administration of ALA. Both localization patterns and amounts of ALA-induced porphyrins in the BCC were studied. The ALA-induced porphyrins were localized only in the superficial layers of the noduloulcerative BCC lesions after topical application of 20% ALA alone for 3 h. However, both the penetration of ALA into deep lesions and the production of the ALA-induced porphyrin fluorescence were increased after topical administration of 20% ALA and 20% DMSO/4% EDTA for 3 h. Prior treatment with 99% DMSO for 15 min further enhanced the ALA penetration into the BCC lesions after topical application of the ALA/DMSO/EDTA mixture and produced more ALA-induced porphyrins by a factor of about three compared with those treated with ALA alone. The penetration of ALA into the deep BCC lesions could also be increased by prolonging the time of topical application of 20% ALA/4% EDTA to 29–48 h (without DMSO). Intravenous injection of ALA led to a more homogeneous distribution of the ALA-derived porphyrins in the whole noduloulcerative BCC lesions.