Palladium-catalyzed hydrosilylation of ynones to access silicon-stereogenic silylenones by stereospecific aromatic interaction-assisted Si–H activation

Hydrosilylation is one of the most important reactions in synthetic chemistry and ranks as a fundamental method to access organosilicon compounds in industrial and academic processes. However, the enantioselective construction of chiral-at-silicon compounds via catalytic asymmetric hydrosilylation remained limited and difficult. Here we report a highly enantioselective hydrosilylation of ynones, a type of carbonyl-activated alkynes, using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand. The stereospecific hydrosilylation of ynones affords a series of silicon-stereogenic silylenones with up to 94% yield, 20:1 regioselectivity and 98:2 enantioselectivity. The density functional theory(DFT) calculations were conducted to elucidate the reaction mechanism and origin of high degree of stereoselectivity, in which the powerful potential of aromatic interaction in this reaction is highlighted by the multiple C–H-π interaction and aromatic cavity-oriented enantioselectivitydetermining step during desymmetric functionalization of Si–H bond.     

Numerical study of aD-dimensional periodic Lorentz gas with universal properties

We give the results of a numerical study of the motion of a point particle in ad-dimensional array of spherical scatterers (Sinai's billiard without horizon). We find a simple universal law for the Lyapounov exponent (as a function ofd) and a stretched exponential decay for the velocity autocorrelation as a function of the number of collisions. The diffusion seems to be anomalous in this problem. Ergodicity is used to predict the shape of the probability distribution of long free paths. Physical interpretations or clues are proposed.     

A path-following version of the Todd-Burrell procedure for linear programming

We propose a path-following version of the Todd-Burrell procedure to solve linear programming problems with an unknown optimal value. The path-following scheme is not restricted to Karmarkar's primal step; it can also be implemented with a dual Newton step or with a primal-dual step.This work has been completed with the support from the Fonds National Suisse de la Recherche Scientifique, grant 12-34002.92.     

Structure determination of a tetradecapeptide mimicking the RXVRG consensus sequence recognized by a Xenopus laevis skin endoprotease: An approach based on simulated annealing and 1H NMR

Summary The tetradecapeptide of sequence H-Asp-Val-Asp-Glu-Arg ⁵-Asp-Val-Arg-Gly⁹-Phe-Ala-Ser-Phe-Leu-NH₂ is recognized by a putative maturation endoprotease of the Xenopus laevis skin, which cleaves between Arg⁸ and Gly⁹. A conformational search has been performed on this peptide by simulated annealing calculations. Two different models in agreement with the NMR data were found. The conformational difference between the two types of model is located in the consensus sequence, i.e., from Arg⁵ to Gly⁹.     

Palladium-catalyzed synthesis of 3-trifluoromethylated 1,3-dienes from acrylate derivatives and BTP

Here we reported a Pd-catalyzed coupling reaction between acrylate derivatives and BTP (2-bromo-3,3,3-trifluoropropene) to access 3-trifluoromethylated 1,3-dienes. The reaction allows the formation of the corresponding products in good to excellent yields and moderate Z/E diastereoisomeric ratios. This method broadens the current toolbox to access 3-trifluoromethylated 1,3-dienes.     

Probing new approaches using atmospheric pressure photo ionization for the analysis of brominated flame retardants and their related degradation products by liquid chromatography-mass spectrometry

Atmospheric pressure photo ionisation has been evaluated for the analysis of brominated flame retardants and their related degradation products by LC-MS. Degradation mixtures obtained from the photochemical degradation of tetrabromobisphenol A and decabromodiphenylether were used as model systems for the assessment of the developed methodology. Negative ion mode gave best results for TBBPA and its degradation compounds. [M - H]- ions were formed without the need of using a doping agent. MS and MS/MS experiments allowed the structural identification of new TBBPA "polymeric" degradation compounds formed by attachment of TBBPA moieties and/or their respective cleavage products. In the case of polybromodiphenylethers, the positive mode provided M*+ ions and gave better results for congeners ranging from mono- to pentabromodiphenylethers whereas for higher bromination degrees, the negative ion mode (providing [M - Br + O]- ions) was best suited. Under both positive and negative ionisation modes, the use of toluene as doping agent gave better results. Liquid chromatography-mass spectrometry by means of atmospheric pressure photo-ionisation was applied to the analysis of aromatic brominated flame retardants and their degradation products. This methodology proved to be particularly useful, for the characterisation and structural identification of some compounds which are not amenable to GC-MS, especially in the case of apolar "polymeric" degradation products of tetrabromobisphenol A investigated in this work.     

UVB-induced Cyclobutane Pyrimidine Dimer Frequency Correlates with Skin Cancer Mutational Hotspots in p53

Abstract— Ultraviolet light has been identified as the major carcinogen in skin cancer and the p53 tumor suppressor gene is a major target for UV-induced mutations. The mutations are probably caused by unrepaired UV-induced cyclobutane pyrimidine dimers (CPD) and possibly by the less frequent pyrimidine (6-4) pyrimidone photoproducts. While hot spots for p53 mutations in human nonmela-noma skin tumors correspond quite well to slow spots for CPD repair in cultured cells irradiated with the model mutagen 254 nm UVC (which is not present in terrestrial sunlight), they do not all coincide with sequences that are initially frequently damaged by 254 nm UVC. Using LMPCR (ligation-mediated polymerase chain reaction), we show that environmentally relevant UVB light induces CPD at CC and PyrmC positions much more frequently than does UVC light, and that all eight skin cancer hot spots in p53 are also hot spots for UVB-induced CPD. Our results show that methylation of dipyrimidine sites (PyrmCpG) is associated with an increase rate of CPD formation upon UVB irradiation. Consequently, DNA methylation may increase the mutagenic potential of UVB and explains that several p53 mutation hot spots are found at PyrmCpG. The distribution patterns of CPD formation and the photofootprint patterns found along exons 5 and 6 of p53 gene are suggestive of DNA folding into nucleosomes.     

Validation of a real-time monitoring method for aniline in freshwater by high-performance liquid chromatography on porous graphitic carbon/electrospray ionization tandem mass spectrometry

Aniline is an anthropogenic organic compound widely used in polymer, rubber, pharmaceutical and dye industries but also used in biodegradability assays of chemical compounds as a positive biodegradation standard. By the two approaches, the rapid determination of aniline is necessary because of the high toxicity of aniline on hemoglobin. A high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method for the determination of aniline in water is described here. This method, using benzylamine as internal standard, was validated. No time-consuming sample preparation was needed. A rapid separation (7 min between two chromatographic runs) of aniline and benzylamine was performed on a Hypercarb porous graphitic carbon column using a gradient of methanol and 100 mM formic acid. The obtained limits of detection and quantification were 10 and 1 ng/mL, respectively. The response for aniline was quadratic. We show that this problem could be circumvented by showing that the [calculated concentration = f(introduced concentration)] function was linear. The linearity range was 10-1000 ng/mL. An example of an application consisting of an aniline 42-day degradation kinetic in water was demonstrated.     

Multidimensional statistical analysis applied to electron ionization mass spectra to determine steroid stereochemistry

The differentiation of stereoisomers on the basis of their mass spectra only is usually a difficult challenge even when an informative ionization technique such as electron ionization is used; this is particularly the case for steroids. In this study, multivariate statistical techniques have been applied to the mass spectra of derivatized 5xi-androstane-3xi,17xi-diols (xi = alpha,beta) in order to investigate the possibility of discrimination among the different isomers. After collection of the data from the mass spectra (20 replicates for each of the 8 isomers), each ion was considered as a statistical variable and each mass spectrum as an observation. The more discriminative variables (42 out of the 160 initial ones) were selected using the analysis of variance technique (ANOVA). Thereafter, a linear discriminant analysis (LDA) allowed us to set up a predictive model for stereochemistry determination. The two-dimensional graphical display of the 160 observations on the basis of the canonical variables derived from LDA made it possible to separate the eight isomers. The discrimination of 5alpha and 5beta isomers as well as 3alpha and 3beta was unambiguous, whereas, the discrimination of 17alpha and 17beta epimers was less obvious. The robustness of the model was checked with 40 mass spectra recorded over a 6-month period on different quadrupole mass spectrometers and under different signal acquisition conditions. The percentage of correct assignment of these 'unknown' stereoisomers was 92%; only three 17alpha and 17beta epimers were not correctly plotted in the expected zone. Nevertheless, the performance score was better than those observed with traditional mass spectral libraries. Furthermore, this statistical approach allowed us to identify the main fragment ions involved in the discrimination between isomers: m/z 256 and 421 for isomers 5a-5b; m/z 241 and 331 for isomers 5alpha3alpha-5alpha3beta; m/z 143 and 162 for isomers 5beta3alpha-5beta3beta; and m/z 255 for epimers 17alpha-17beta.     

New multiresidue analytical method dedicated to trace level measurement of brominated flame retardants in human biological matrices

A new method has been developed for the multi-residue measurement of the main brominated flame retardants (alpha- and gamma-hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBP-A) and polybrominated diphenyl ethers including decabromodiphenyl ether) in human biological matrices (serum, adipose tissue and breast milk). The proposed sample preparation procedure focused on reduced solvent and consumable consumption and associated procedural contamination, as well as reduced sample size. This protocol was fully validated and was proved to be suitable for identification of brominated flame retardant residues at ultra-trace level, as attested by preliminary results on real samples.