One-pot synthesis of pentacyclic diamines from quinolines by a new Zn/AcOH-promoted cascade reaction

A simple and efficient method for the one-pot synthesis of pentacyclic diamines from quinolines is described. It involves a new Zn/AcOH-promoted cascade reaction, in which two C[bond]C bonds and four to five stereogenic centers are established under mild conditions. The regiochemistry of the dimerization and cyclization step is governed by substituent effects, allowing access to a head-to-head (2, 3) or head-to-tail skeleton (4, 5).     

Multi-step reactions of N-monosubstituted (polyfluoroalkane)thioamides with alkyllithium reagents

Reactions of N-alkyl- or N-aryl(perfluoroalkyl)thiocarboxamides with alkyl lithium reagents are described. Trifluorothioacetamides are converted into the corresponding lithium salts. Compounds bearing a long polyfluorinated chain terminated by a CHF₂ group and compounds containing an N-alkyl substituent with a proton adjacent to nitrogen react further via a multi-step reaction sequence involving HF elimination and then vinylic fluorine substitution and/or S_N′ type fluorine substitution. These transformations led to unsaturated N-monosubstituted polyfluorinated thioamides.     

Efficient mutation detection in MEN1 gene using a combination of single-strand conformation polymorphism (MDGA) and heteroduplex analysis

For facilitated genotypic analysis of multiple endocrine neoplasia type 1 (MEN1), a familial syndrome associated with tumors of the parathyroid and neuroendocrine tissues, we developed two screening methods, heteroduplex mutation assay (HMA) and mutation detection gel analysis (MDGA), both based on electrophoretic discrimination of polymerase chain reaction (PCR) products, to detect the mutations. Forty-three genomic DNA samples were used for the evaluation of these techniques. The whole coding region of MEN1 was PCR-amplified with fluorescent primers and then denatured/renatured before electrophoresis on an automated sequencer. 100% of the mutations were detected, subsequently confirmed and identified by sequencing. "Negative" samples were used to evaluate the specificity and reproducibility of the two techniques. The combination of the two methods allows high throughput cost-effective mutation screening which is less laborious than systematic sequencing of the whole coding region of MEN1. Together, these methods provide an efficient screen for MEN1 mutations.     

Monitoring protein interactions in the living cell through the fluorescence decays of the cyan fluorescent protein.

Using fluorescence lifetime microspectroscopy and imaging techniques, we have studied the fluorescence of cyan fluorescent protein (CFP) transiently expressed in HEK-293 cells, in the presence or absence of its fluorescence resonance energy transfer (FRET) partner, yellow fluorescent protein (YFP). When the two proteins are attached through a 27-amino-acid linker, a 33 % average efficiency of intramolecular energy transfer is accurately determined inside the cell. Additionally, we observe a systematic quenching of the CFP fluorescence with increasing levels of protein expression. This quenching cannot be accounted for by formation of the previously described dimer of GFP-related proteins, since its magnitude is unchanged when the fluorescent proteins carry the mutation A206K shown to dissociate this dimer in vitro. Even when the intracellular protein concentration largely exceeds the in vitro dissociation constant of the dimer, self-association remains undetectable, either between free proteins or intramolecularly within the CFP-YFP construct. Instead, the detailed concentration effects are satisfactorily accounted for by a model of intermolecular, concentration-dependent energy transfer, arising from molecular proximity and crowding. In the case of CFP alone, we suggest that self-quenching could result from a pseudo-homo FRET mechanism between different, spectrally shifted emissive forms of the protein. These phenomena require careful consideration in intracellular FRET studies.     

Temperature effect on tyre-road noise

Tyre-road noise emission decreases when the outdoor temperature increases, with a variation that can exceed −0.1 dB(A)/°C. This effect depends on tyre-road combination, but semi-generic corrections can improve the accuracy of tyre-road noise measurements. In this paper, the variation of pass-by noise level of a passenger car at 90 km/h with temperature is investigated, on seven types of road surfaces, under different temperature conditions. A good correlation between air, road surface and tyre temperature is outlined. A linear relationship between noise level and air temperature variations is observed for bituminous pavements, of about −0.1 dB(A)/°C, but reduced to −0.06 dB(A)/°C for pavements having porosity. No temperature effect is observed on cement concrete pavements. A spectral analysis shows that the temperature effect is highest in low and high frequency range, what can be explained by generating mechanisms rather than propagation.     

A synthesis of new pyrrolo[3,2‐c]quinolines

A synthesis of pyrrolo[3,2‐c]quinolines substituted in the 7‐ and 8‐ positions by methoxy groups and in the 3‐ position by an amido group is described. The structures were designed to have a crescent shape, a planar fused cyclic moiety with two ortho methoxy groups and ionisable amino or amidinic group at pH 7.     

Respiratory adaptations to the deep-sea hydrothermal vent environment: the case of Segonzacia mesatlantica, a crab from the Mid-Atlantic Ridge

Segonzacia mesatlantica (Crustacea; Decapoda; Brachyura) is the only endemic crab species known from the Mid-Atlantic Ridge (MAR) hydrothermal vents. Known from all explored sites in the Atlantic, its wide distribution makes this species a model to study physiological adaptation, and specifically respiratory strategies. Native haemocyanin (Hc) comprises four non-covalent associations in equilibrium formed by monomers, hexamers, dodecamers and octadecamers made up of approximately 75 kDa polypeptide chains. Four different amino acid chains are observed with a molecular mass ranging from 75,234 to 75,972 Da. Experiments carried-out under pressure suggested that the percentage of monomer increased in the haemolymph under hypoxic condition. We have also observed a shift of the proportion of the two dodecamer series, suggesting a rapid modification of the Hc phenotype between hypoxic and hyperoxic conditions. Native Hc possesses a high oxygen affinity ( P50 = 2.2 Torr at 15 degrees C and pH 7.5), a large Bohr effect (Deltalog P50 / DeltapH approximately -2.7) and a slightly reverse temperature effect (DeltaH = +17.19 kJ mol(-1). The composition of Segonzacia haemolymph is similar to that of other littoral species except for the large enrichment in free copper and zinc. As for other species from hydrothermal vent sites, Segonzacia haemolymph possesses a higher buffer capacity than littoral species. Moreover, species from the hydrothermal vent decapods from Pacific hydrothermal vent that encounter higher CO2 content in their environment have a higher buffer capacity than Atlantic vent species. The results presented are discussed in relation with the physico-chemical characteristics of the hydrothermal vent environment.     

Synthesis of new artemisinin-derived dimers by self-cross-metathesis reaction

[reaction: see text] New artemisinin-derived dimers, fluorinated or not, have been prepared by a self-cross metathesis reaction in the presence of first- or second-generation ruthenium catalysts without degradation of the endoperoxide bridge and with a good E/Z selectivity (up to 100:0).