New fully automated gas chromatographic analysis of urinary S‐phenylmercapturic acid in isotopic dilution using negative chemical ionization with isobutane as reagent gas

The determination of urinary S‐phenylmercapturic acid (S‐PMA) represents the most reliable biomarker to monitor the intake risk of airborne benzene. Recently, the European Chemical Agency deliberated new occupational exposure limits for benzene and recommended an S‐PMA biological limit value of 2‐μg/g creatinine. This limit is an order of magnitude lower than the previous one, and its determination constitutes a challenge in the analytical field. We developed and validated a method that allows the fully automated and sensitive determination of S‐PMA by the use of gas‐chromatography negative chemical ionization tandem mass spectrometry in isotopic dilution. For negative chemical ionization, we selected a mixture of 1% isobutane in argon as reactive gas, by studying its chemical ionization mechanism and optimal parameters compared with pure isobutane or pure methane. This gas mixture produces a more abundant signal of the target analyte than isobutane or methane, and it extended the operative lifetime of the ion source, enabling us to start a high‐throughput approach of the S‐PMA analysis. Moreover, energy‐resolved mass spectrometry experiments were carried out to refine the MS/MS analysis conditions, testing nitrogen and argon as collision gases. The method optimization was pursued by a chemometric model by using the experimental design. The quantification limit for S‐PMA was 0.10 μg/L. Accuracy (between 98.3% and 99.6%) and precision (ranging from 1.6% to 6.4%) were also evaluated. In conclusion, the newly developed assay represents a powerful tool for the robust, reliable, and sensitive quantification of urinary S‐PMA, and because of its automation, it is well suited for application in large environmental and biological monitoring.     

Synthesis of the isoquinoline alkaloid, crispine C

The first total synthesis of the isoquinoline alkaloid, crispine C is described in seven steps using a Henry reaction and the Pictet-Gams variant of the Bischler-Napieralski reaction to effect the key transformations.     

Protecting group free, stereocontrolled synthesis of β-halo-enamides

Enamides, dienamides, and enynamides are important building blocks in synthetic, biological, and medicinal chemistry as well as materials science. Despite the extensive breath of their potential utility in synthetic chemistry, there is a lack of simple, high-yielding methods to deliver them efficiently and as single isomers. In this paper, we present a novel, protecting group free, efficient, and stereoselective approach to the generation of β-halo-enamides. The methodology presented provides a robust synthetic platform from which E- or Z-enamides can be generated in good yields and with complete stereocontrol.     

Terpene biosynthesis in the nudibranch Doriopsilla areolata

Biogenesis of the enantiomeric sesquiterpenes 1 and 5 of the marine nudibranch Doriopsilla areolata was investigated by feeding of [1-(13)C]glucose, [1,2-(13)C(2)]glucose, and [1,2-(13)C(2)]acetate. Evidence is presented that supports de novo origin of both compounds via mevalonic acid.     

Photochemistry of ommochrome pigments

The ommochrome pigment present in the eyes of Loligo Vulgaris was extracted with a butanol-acetic acid-hydrochloric acid solution. The extraction mixture was examined before and after irradiation by visible light. A phenoxazinone ring opening together with a photo-induced solvent addition, causing a yellow-red batho-chromic shift, were observed and a plausible explanation of the process has been carried out and is reported on the basis of the isolated products.     

On the mathematical form of de Broglie's cyclical action integral

Mathematical expressions for the entropyS, the average information gained per trial (ī) from information theory, and the de Broglie cyclical action integralA from his reinterpretation of wave mechanics are shown to be similar. The importance of this observation in our understanding ofS andī is considered. Furthermore, the similarity in the mathematical form of these functions indicates a possible route to further interpretation of de Broglie'sA and the nature of his “hidden thermostat.”     

Oxidation of 2-amino-4-methylphenol in acidic medium

The oxidation of 2-amino-4-methylphenol 1 , by ferricyanide, in acetic acid yields benzoquinonimine 2 , phenoxazinonimine 3 and 4 , triphenodioxazines 5 and phenoxazinone 6 . The reaction mechanism seems to start with an electrophilic substitution of the quinonimine, from 1 , on the electron rich 1 , rather than with a nucleophilic attack of 1 on the arising quinonimine.     

New C16 fatty-acid-based oxylipin pathway in the marine diatom Thalassiosira rotula

An unprecedented series of C16 oxylipins (1-8) has been characterized from the marine diatom Thalassiosira rotula. Absolute stereochemistry of the major alcohols 1 and 3 was determined to be 9S by spectroscopic and chemical methods. All the described products are formally derived by unprecedented enzymatic oxidation of C16 fatty acids. Conversion of hexadeca-6,9,12-trienoic acid (C16:3 omega-4) into 3 unequivocally established the occurrence of (at least) a specific 9S-oxygenase activity. To the best of our knowledge, the present data reveal for the first time the existence of an organic network of oxygenase-mediated transformations that require C16 fatty acids as substrates in living cells.     

Observed and calculated 1H- and 13C-NMR chemical shifts of substituted 5H-pyrido[3,2-a]- and 5H-pyrido[2,3-a]phenoxazin-5-ones and of some 3H-phenoxazin-3-one derivatives

Carbon and proton NMR spectra of several substituted 5H-pyrido[3,2-a]-, 5H-pyrido[2,3-a]phenoxazin-5-ones and 3H-phenoxazin-3-one derivatives have been assigned, and the experimental chemical shifts have been compared with the results of density functional calculations employing large basis sets. Solvent effects were explored by means of the polarizable continuum method (PCM), while the (limited) side-chain flexibility of the compounds has been addressed by Boltzmann averaging of the computed spectral parameters over different conformational minima. Overall, the calculated shifts reproduce well the experiment results; thus, the computational procedure represents a feasible and useful complement to multidimensional NMR experiments in the assignment process.     

Sun Exposure, Sunscreen and Their Effects on Epidermal Langerhans Cells

This study examined the effects of chronic and current sun exposure on the number of Langerhans cells in epidermal sheets of UV-exposed and unexposed skin of the arms and assessed the effect of sunscreens. Participants were enrolled in a skin cancer prevention trial and had been using sunscreen daily for the previous 3 years. There were significantly fewer Langerhans cells on the exposed (463 cells/mm2) than on the unexposed forearm (528 cells/mm2) (P = 0.0001). High sun exposure in the previous 2 weeks and a history of predominantly outdoor occupations were both associated with a reduced number of Langerhans cells, although age and other biological indicators of chronic exposure were not associated. Sunscreen use was protective against the effects of current but not chronic sun exposure, with a suggestion of a greater effect at higher levels of exposure. Unexpectedly, people with a past history of nonmelanoma skin cancer had more Langerhans cells in both the exposed and the unexposed skin. These results emphasize the need for continued public health education to protect the immune system from the damaging effects of UV radiation .