Synthesis of the o-quinones and other oxidized metabolites of polycyclic aromatic hydrocarbons implicated in carcinogenesis

Efficient new syntheses of the o-quinone derivatives of benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding o-catechols, trans-dihydrodiols, and the corresponding anti- and syn-diol epoxides.     

Distribution of single DNA molecule electrophoretic mobilities in semidilute and dilute hydroxyethylcellulose solutions

The distribution of center of mass electrophoretic mobility mobilities and normalized migration time of up to 1080 lambda DNA molecules per experiment were measured in both semidilute hydroxyethylcellulose HEC/0.5 x Tris-borate-EDTA (TBE) solutions and dilute HEC/0.5 x TBE solution by high-speed video microscopy. Measurements were made microscopically over a short migration distance in homogeneous DNA HEC/0.5 x TBE solution and after electrophoretic migration of a plug of DNA through 7 cm. Video at 120 frames/s (semidilute HEC solution) and 236 frames/s (dilute HEC solution) allowed visualization with adequate resolution for single molecule mobility measurements. The electrophoretic migration times and band shapes predicted from the measurements corresponded well with those measured by conventional capillary electrophoresis (CE) in both semidilute and dilute HEC. In semidilute solution, the band width predicted by a square root of time scaling is in good agreement with the results of conventional CE. However, in dilute solution the precision of the measurements was not good enough to allow scaled estimates of band widths.     

K-region oxides and imines of benzo[b]phenanthro[2,3-d]thiophene and benzo[b]phenanthro[3,2-d]thiophene

The syntheses of the K-oxides and K-imine derivatives of benzo[b]phenanthro[2,3-d]thiophene and benzo-[b]phenanthro[3,2-d]thiophene are described. The parent hydrocarbons 1 and 2 were oxidized with osmium tetroxide and sodium metaperiodate, and the dialdehydes 12 and 18 so formed, cyclized to the corresponding epoxides 1a,12b-dihydrobenz[b]oxireno[9,10]phenanthro[2,3-d]thiophene ( 7 ) and 1a,12b-dihydrobenz-[b]oxireno[9,10]phenanthro[3,2-d]thiophene ( 13 ). Reaction of the oxiranes with sodium azide gave mixtures of azido-alcohols that, in turn, were transformed to the thiaarene imines 1a,12b-dihydro-1H-benz[b]azirino-[9,10]phenanthro[2,3-d]thiophene ( 8 ) and 1a,12b-dihydro-1H-benz[b]azirino[9,10]phenanthro[3,2-d]thiophene ( 14 ), respectively, with the aid of tri-n-butylphosphine.     

Intrinsic defects in irradiated and annealed GaAs detected by FTIR

GaAs has been subjected to fast neutron or electron irradiations up to doses of 2×10¹⁹ n cm^–2 and 10¹⁹ e^– cm^–2 respectively and subsequently annealed to temperatures of 500°C. Infrared absorption spectra (20–700 cm^–1), measured at 20 K, show that the induced one-phonon absorption depends on the nature of the radiation. Resonant modes, at 45 cm^–1 and 119 cm^–1, and a broad line at 328 cm^–1 were found in neutron irradiated material, whereas in electron irradiated material only the 45 cm^–1 feature was detected. These spectroscopic features are interpreted as vibrational modes arising from intrinsic defect centres.     

Activation of acyl phosphate monoesters by lanthanide ions: enhanced reactivity of benzoyl methyl phosphate

Acyl phosphate monoesters are intermediates in many biochemical acylation reactions, such as those involving aminoacyl adenylates. Benzoyl methyl phosphate, a typical acyl phosphate monoester, is slowly hydrolyzed in neutral solutions but reacts rapidly with amines. Since biochemical processes of acyl phosphate monoesters involve accelerated reactions with oxygen-centered nucleophiles, we sought catalysts for hydrolysis and methanolysis of benzoyl methyl phosphate to mimic the biochemical outcome. Lanthanide ions are particularly effective catalysts, accelerating reactions much more than comparable levels of magnesium ion. Detailed kinetic analysis of the hydrolysis reactions reveals formation of a 1:1 complex, followed by rapid reaction with a nucleophile. The hydroxide-dependent hydrolysis rate in the europium complex is about 10(5) times that of free substrate with hydroxide. A mechanism that accounts for the data and observed behavior involves bidentate coordination of the metal ion by the acyl phosphate through phosphate and carbonyl oxygens, lowering the energy of the tetrahedral addition intermediate and the associated transition states. The dependence of the metal ion catalyzed process on the concentration of hydroxide ion is consistent with coordinated hydroxide acting as a nucleophile. The reaction of benzoyl methyl phosphate with methanol to form methyl benzoate and methyl phosphate is 30 000 times more rapid in the presence of 0.0001 M lanthanum triflate (in the absence of the metal ion k(obs) = 2.1 x 10(-7) s(-1), at 25 degrees C). Thus, the combination of acyl phosphate esters and lanthanide salts appears to be a promising method for biomimetic acylation of hydroxyl groups.     

A further structural variation of product yield in collisional activation. Study of CH3S+ from dimethyl disulfide with high precursor ion resolution

The isobaric ions CH₃³²S⁺ and CH³⁴S⁺ from dimethyl disulfide were separated and collisionally activated in a four-sector mass spectrometer. The contributions of minor components to the collisional activation spectrum of the unresolved beam are not correctly predicted from consideration of isotope peak corrections using relative intensities of adjacent peaks in the mass spectrum of CH₃SSCH₃, because the isobaric components not only have different cross-sections for fragmentation but also different cross-sections for transmission of the unfragmented beam through the collision gas. Helium collision spectra of the two components are given.     

Analysis of the electronic structure of Hf(Si0.5As0.5)As by X-ray photoelectron and photoemission spectroscopy

The ternary hafnium silicon arsenide, Hf(Si_xAs_1−x)As, has been synthesized with a phase width of 0.5?x?0.7. Single-crystal X-ray diffraction studies on Hf(Si_0.5As_0.5)As showed that it adopts the ZrSiS-type structure (Pearson symbol tP6, space group P4/nmm, Z=2, a=3.6410(5) Å, c=8.155(1) Å). Physical property measurements indicated that it is metallic and Pauli paramagnetic. The electronic structure of Hf(Si_0.5As_0.5)As was investigated by examining plate-shaped crystals with laboratory-based X-ray photoelectron spectroscopy (XPS) and synchrotron radiation photoemission spectroscopy (PES). The Si 2p and As 3d XPS binding energies were consistent with assignments of anionic Si¹⁻ and As^1-. However, the Hf charge could not be determined by analysis of the Hf 4f binding energy because of electron delocalization in the 5d band. To examine these charge assignments further, the valence band spectrum obtained by XPS and PES was interpreted with the aid of TB-LMTO band structure calculations. By collecting the PES spectra at different excitation energies to vary the photoionization cross-sections, the contributions from different elements to the valence band spectrum could be isolated. Fitting the XPS valence band spectrum to these elemental components resulted in charges that confirm that the formulation of the product is Hf²⁺[(Si_0.5As_0.5)As]²⁻.     

Use of a quadrupole linear ion trap mass spectrometer in metabolite identification and bioanalysis

A new type of quadrupole linear ion trap mass spectrometer, Q TRAP trade mark LC/MS/MS system (Q TRAP trade mark ), was evaluated for its performance in two studies: firstly, the in vitro metabolism of gemfibrozil in human liver microsomes, and, secondly, the quantification of propranolol in rat plasma. With the built-in information-dependent-acquisition (IDA) software, the instrument utilizes full scan MS in the ion trap mode and/or constant neutral loss scans as survey scans to trigger product ion scan (MS(2)) and MS(3) experiments to obtain structural information of drug metabolites 'on-the-fly'. Using this approach, five metabolites of gemfibrozil were detected in a single injection. This instrument combines some of the unique features of a triple quadrupole mass spectrometer, such as constant neutral loss scan, precursor ion scan and multiple reaction monitoring (MRM), together with the capability of a three-dimensional ion trap. Therefore, it becomes a powerful instrument for metabolite identification. The fast duty cycle in the ion trap mode allows the use of full product ion scan for quantification. For the quantification of propranolol, both MRM mode and full product ion scan in the ion trap mode were employed. Similar sensitivity, reproducibility and linearity values were established using these two approaches. The use of the product ion scan mode for quantification provided a convenient tool in selecting transitions for improving selectivity during the method development stage.     

Characterization of Silica-Containing Aluminum Hydroxide and Oxide Aerogels

Pure and silica-containing Al hydroxide aerogels were prepared by the supercritical drying method. The samples were later calcined, giving rise to alumina and Si–Al mixed oxides. The materials were characterized from the points of view of their bulk and surface structures. The Si-free material before calcination is well-crystallized boehmite that converts to γ-alumina by calcination. The silica-containing hydroxides are composed of boehmite layers with silicates in the interlayer region. The resulting mixed oxides present silica essentially in the bulk. The surface structure of alumina seems poorly sensitive to silica addition. Surface silanol groups appear only for SiO₂more than 4%. No Brønsted acidity appears. Silica addition allows mixed oxides with higher surface areas to be obtained.     

An interlaboratory-verified method for the determination of vitamins A and E in milk- and soy-based infant formula by liquid chromatography with matrix solid-phase dispersion extraction

An interlaboratory-verified, liquid chromatographic (LC) method is presented for determination of all-racemic alpha-tocopheryl acetate and retinyl palmitate in infant formula. The extraction procedure uses matrix solid-phase dispersion. A sample is mixed with C18, and the mixture is packed into a reservoir and eluted with selective solvents to extract the analytes. After evaporation and filtration, the sample extract is injected directly into a normal-phase LC system with fluorescence detection. All-racemic alpha-tocopheryl acetate and retinyl palmitate are quantitated isocratically with a mobile phase of hexane containing isopropanol at 0.2% (v/v) and 0.125% (v/v), respectively. A nonfortified zero control reference material (ZRM) was spiked at 5 levels, with 5 replicate analyses of 1/2x, x, 2x, 4x, and 16x where "x" represents the minimum levels of 250 IU/100 kcal (vitamin A) and 0.7 IU/100 kcal (vitamin E) as specified in Title 21 of the Code of Federal Regulations, part 107.100. Recoveries of retinyl palmitate ranged from 83.8 to 107%, and those of all-racemic alpha-tocopheryl acetate ranged from 87.7 to 108%. Two additional laboratories analyzed the ZRM samples at 4 spiking levels with 6 replicates. Recoveries of retinyl palmitate and all-racemic alpha-tocopheryl acetate ranged from 92.2 to 104% and from 91.7 to 101%, respectively, in the second laboratory. Recoveries of retinyl palmitate and all-racemic alpha-tocopheryl acetate ranged from 85.3 to 97.0% and from 86.6 to 110%, respectively, in the third laboratory. Relative standard deviations for all 3 laboratories ranged from 0.2 to 7.5% with an average of 2.9%. In addition, each laboratory analyzed a commercial milk- and commercial soy-based infant formula. Excellent agreement in results was obtained between the 3 laboratories for vitamins A and E in all matrixes.