Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as follows: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1 ± 0.1) was measured from both (E)-C6H5CH═C(CH3)CONHCH3 and (E)-C6H5CD═C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7 ± 0.1) was observed from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene and styrene-d8. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH═CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH═CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH═CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH═CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1 ± 0.1 and +1.5 ± 0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, ΔH⧧ = 20 ± 2 kcal mol–1 and ΔS⧧ = −42 ± 5 eu. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies

Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

<p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) ₂, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)₃(GlcNAc)₂], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)₂.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p

Effect of thermal residual stresses on matrix failure under transverse tension at micromechanical level: A numerical and experimental analysis

International audienceIn the present work the influence at micromechanical scale of thermal residual stresses, originated in the cooling down associated to the curing process of fibrous composites, on inter-fibre failure under transverse tension is studied. In particular, the effect of the presence of thermal residual stresses on the appearance of the first debonds is discussed analytically, whereas later steps of the mechanism of damage, i.e. the growth of interface cracks and their kinking towards the matrix, are analysed by means of a single fibre model and making use of the Boundary Element Method. The results are evaluated applying Interfacial Fracture Mechanics concepts. The conclusions obtained predict, at least in the case of dilute fibre packing, a protective effect of thermal residual stresses against failure initiation, the morphology of the damage not being significantly affected in comparison with the case in which these stresses are not considered. Experimental tests are carried out, the results agreeing with the conclusions of the numerical analysis

Medications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism

Bruxism is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. It can occur during sleep, indicated as sleep bruxism, or during wakefulness, indicated as awake bruxism. Exogenous risk indicators of sleep bruxism and/or awake bruxism are, among others, medications and addictive substances, whereas also several medications seem to have the potential to attenuate sleep bruxism and/or awake bruxism. The objective of this study was to present a narrative literature on medications and addictive substances potentially inducing or aggravating sleep bruxism and/or awake bruxism and on medications potentially attenuating sleep bruxism and/or awake bruxism. Literature reviews reporting evidence or indications for sleep bruxism and/or awake bruxism as an adverse effect of several (classes of) medications as well as some addictive substances and literature reviews on medications potentially attenuating sleep bruxism and/or awake bruxism were used as starting point and guidelines to describe the topics mentioned. Additionally, two literature searches were established on PubMed. Three types of bruxism were distinguished: sleep bruxism, awake bruxism and non-specified bruxism. Generally, there are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism. There are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism.Peer reviewe

Measurement of Branching Fractions for B→ηcK(∗)B\to \eta_c K^{(*)} Decays

We report measurements of branching fractions for charged and neutral $B\to \eta_c K$ decays where the $\eta_c$ meson is reconstructed in the $K_S^0 K^{\pm}\pi^{\mp}, K^+ K^- \pi^0, K^{*0} K^-\pi^+$ and $p \bar{p}$ decay channels. The neutral $B^0$ channel is a CP eigenstate and can be used to measure the CP violation parameter $\sin 2\phi_1$. We also report the first observation of the $B^0\to \eta_c K^{*0}$ mode. The results are based on an analysis of 29.1 fb$^{-1}$ of data collected by the Belle detector at KEKB.Comment: To appear in Physical Review Letter