Rhodium-Catalyzed Copper-Assisted Intermolecular Domino C−H Annulation of 1,3-Diynes with Picolinamides: Access to Pentacyclic π-Extended Systems

A new mode of reactivity of 1,3-diynes in rhodium-catalyzed oxidative annulation reactions has enabled the rapid assembly of extended π systems from readily available picolinamide derivatives. The process involves a double C−H bond activation and the iterative annulation of two 1,3-diyne units, with each alkyne moiety engaged in an orchestrated insertion sequence with high regiocontrol, leading to the formation of five new C−C bonds and the construction of four fused rings in a single operation. Either isoquinoline-1-carboxamides or fused polycyclic systems can be accessed by a switch in the regioselectivity of the second diyne insertion depending on the reaction conditions. DFT theoretical calculations have elucidated that the cooperative participation of both rhodium and copper in substrate activation, favored in the presence of excess of the copper(II) salt, is key to such a reversal of regioselectivity and subsequent multiple cyclization leading to fused polycyclic products. The role of copper was found to be essential in assisting both multiple insertion and rhodium-walking sequences, with the implication of intermediates with a Rh−Cu bond (2.60 Å).     

Quantitation of cytidine-5′-monophospho-N-acetylneuraminic acid in human leukocytes using LC–MS/MS: method development and validation

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP-Neu5Ac as well as N-acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography–tandem mass spectrometry methods. A fit-for-purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol–water mixture and the leukocyte extract was used for LC–MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP-Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.     

Comparing the effect of nanofillers as thermal stabilizers in low density polyethylene

A study of the thermal degradation under inert and oxidative conditions of LDPE and three 5-wt% nanocomposites has been performed. The bases of comparison were the geometries of the nanofillers (spherical, fibrous and laminar) and the sample thickness. Homogeneous and well-dispersed materials were obtained with the three nanoparticles, ensuring a relevant comparative analysis.The thermal degradation curves obtained from TGA under nitrogen flow did not show significant differences in behaviour within the nanocomposites and the reference LDPE. However, the results for the thermo-oxidation study showed a strong stabilization effect for both fibrous and laminar silicates, but not for the spherical silica nanoparticles. A kinetic study of the degradation under isothermal conditions showed that the nanocomposites made from fibrous and laminar silicates degraded following the mechanisms observed for thin films independent of the sample thickness. These results suggested the occurrence of a protective layer against thermo-oxidation on the film surface. Chemical analysis of the degraded surfaces by IR and EDX measurements gave data to explain these differences in behaviour.     

Comparisons Between Largest Order Statistics from Multiple-outlier Models with Dependence

We study stochastic comparisons between the largest order statistics from samples which may contain outliers. The data in each sample can also be dependent. Under these assumptions we study three cases. In the first one we consider the general case without additional assumptions. In the second we assume that the data come from two different distributions. In the third one we assume that the data come from a proportional hazard rates model. The results obtained here can be applied to compare parallel systems. Some illustrative examples are provided.     

Layer-by-layer PMIRRAS characterization of DMPC bilayers deposited on a Au111 electrode surface

A combination of Langmuir-Blodgett and Langmuir-Schaefer techniques was employed to deposit 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at a gold electrode surface. One leaflet consisted of hydrogen-substituted acyl chains, and the second leaflet was composed of molecules with deuterium-substituted acyl chains. This architecture allowed for layer-by-layer analysis of the structure of the bilayer. Photon polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) was used to determine the conformation and orientation of the acyl chains of DMPC molecules in the individual leaflets as a function of the potential applied to the gold electrode. The bilayer is adsorbed onto the metal surface when the field applied to the membrane does not exceed approximately 108 V/m. When adsorbed, the bottom leaflet is in contact with a hydrophobic metal surface, and the top leaflet is interacting with the aqueous solution. The asymmetry of the environment has an effect on the orientation of the DMPC molecules in each leaflet. The tilt angle of the acyl chains of the DMPC molecules in the bottom leaflet that is in contact with the gold is approximately 10 degrees smaller than that observed for the top leaflet that is exposed to the solution. These studies provide direct evidence that the structure of a phospholipid bilayer deposited at an electrode surface is affected by interaction with the metal.     

On the choice of weights profiles in cross-efficiency evaluations

In this paper, we propose a new approach to cross-efficiency evaluation that focuses on the choice of the weights profiles to be used in the calculation of the cross-efficiency scores. It has been claimed in the literature that cross-efficiency eliminates unrealistic weighting schemes in the sense that their effects are cancelled out in the summary that the cross-efficiency evaluation makes. The idea of our approach here is to try to avoid these unreasonable weights instead of expecting that their effects are cancelled out in the amalgamation of weights that is made. To do it, we extend the ideas of the multiplier bound approach to the assessment of efficiency without slacks in Ramón et al. (2010) to its use in cross-efficiency evaluations. The models used look for the profiles with the least dissimilar weights, and also guarantee non-zero weights. In particular, this approach allows the inefficient DMUs to make a choice of weights that prevent them from using unrealistic weighting schemes. We use some examples of the literature to illustrate the performance of this approach and discuss some issues of interest regarding the choice of weights in cross-efficiency evaluations.     

A combined in situ AFM and SEM study of the interaction between celestite (0 0 1) surfaces and carbonate-bearing aqueous solutions

In this paper, we present in situ atomic force microscopy (AFM) observations of the interaction between celestite (SrSO₄) (0 0 1) surfaces and Na₂CO₃ aqueous solutions. The observations indicate that the interaction is characterized by a rapid alteration (carbonatation) and dissolution of the original surface, shortly followed by the formation of a new phase. EDX analyses indicate that the new phase is strontianite (SrCO₃). Its crystallization involves the formation and spreading of islands of about 2.75 nm in height, which chiefly occurs on the step edges of the dissolving celestite substrate. The thickness of the islands remains almost constant during their spreading, which occurs mainly parallel to the celestite [0 1 0] direction. As a result of the progressive coalescence of the islands, a fairly homogeneous epitaxial layer forms on the celestite (0 0 1) face. At the initial stages, the formation of islands on the celestite (0 0 1) faces enhances dissolution, indicating the existence of a coupling between dissolution and crystallization reactions. Our measurements on series of AFM images provided quantitative information about coupled dissolution-growth rates on a nanoscale. The effect of the coupled reactions on the celestite (0 0 1) surface on a microscopic scale was also studied by scanning electron microscopy (SEM).