Highly enantioselective and regioselective copper-catalyzed 1,4 addition of grignard reagents to cyclic enynones

In this letter we describe an unusual result in terms of regioselectivity with respect to copper-catalyzed conjugate additions of various Grignard reagents to cyclic enynones. The use of Cu(OTf)(2) and NHC ligand L1 as the catalyst combination in CH(2)Cl(2) led to the unique formation of the 1,4 adduct. This selectivity does not follow the general trend previously observed in the literature using extended Michael acceptors. Moreover these reactions allowed for the creation of a quarternary stereogenic center with enantioselectivities up to 97% ee.     

L-arginine binding to human inducible nitric oxide synthase: an antisymmetric funnel route toward isoform-specific inhibitors?

Nitric oxide (NO) is an important signaling molecule produced by a family of enzymes called nitric oxide synthases (NOS). Because NO is involved in various pathological conditions, the development of potent and isoform-selective NOS inhibitors is an important challenge. In the present study, the dimer of oxygenase domain of human iNOS (iNOSoxy) complexed to its natural substrate L-arginine (L-Arg) and both heme and tetrahydro-L-biopterin (BH4) cofactors was studied through multiple molecular dynamics simulations. Starting from the X-ray structure available for that complex (PDB: 1NSI ), a 16 ns equilibration trajectory was first obtained. Twelve dynamics of slow extraction of L-Arg out from the iNOSoxy active site were then performed. The steered molecular dynamics (SMD) approach was used starting from three different points of the reference trajectory for a total simulation time of 35 ns. A probable unbinding/binding pathway of L-Arg was characterized. It was suggested that a driving force directed the substrate toward the heme pocket. Key intermediate steps/residues along the access route to the active site were identified along this "funnel shape" pathway and compared to existing data. A quasi-normal mode analysis performed on the SMD data suggested that large collective motions of the protein may be involved in L-Arg binding and that opening the route to the active site in one monomer promoted an inverse, closing motion in the second monomer. Finally, our findings might help to rationalize the design of human iNOS isoform competitive inhibitors.     

Extensions of system signatures to dependent lifetimes: Explicit expressions and interpretations

The concept of system signature was introduced by Samaniego for systems whose components have i.i.d. lifetimes. We consider its extension to the continuous dependent case and give an explicit expression for this extension as a difference of weighted means of the structure function values. We then derive a formula for the computation of the coefficients of these weighted means in the special case of independent continuous lifetimes. Finally, we interpret this extended concept of signature through a natural least squares approximation problem.     

Mono- and dicarbonyl-bridged tricyclic heterocyclic acceptors: synthesis and electronic properties

A series of trialkylsilyl-substituted 2,2'-dithiophene, 4,4'-di-n-hexyl-2,2'-dithiophene, 5,5'-dithiazole, and 2,2'-diselenophene with carbonyl (2a-d) and α-dicarbonyl bridges (3a-d) were prepared from readily available dihalides, using double lithiation followed by trapping with N,N-dimethylcarbamoyl chloride or diethyl oxalate (or N,N-dimethylpiperazine-2,3-dione), respectively. Cyclic voltammetry reveals that the first half-wave reduction potentials for this series of compounds span a wide range, from -1.87 to -0.97 V vs the ferrocene/ferrocenium couple at 0 V (0.1 M (n)Bu(4)NPF(6) in THF). A significant increase of the first half-wave reduction potential (by 0.50-0.67 V) was observed on substitution of the monocarbonyl bridge with α-dicarbonyl. Adiabatic electron affinity (AEA, gas phase) trends determined via density functional theory (DFT) calculations are in good agreement with the electrochemical reduction potentials. UV-vis absorption spectra across the series show a weak absorption band in the visible range, corresponding to the HOMO→LUMO transition within a one-electron picture, followed by a more intense, high-energy transition(s). Single-crystal X-ray structural analyses reveal molecular packing features that balance the interplay of the presence of the bulky substituents, intermolecular π-stacking interactions, and S···O intermolecular contacts, all of which affect the DFT-evaluated intermolecular electronic couplings and effective charge-carrier masses for the crystals of the tricyclic cores.     

Isolation of C-glycosyl xanthones from Coffea pseudozanguebariae and their location

The biochemical composition of leaves from Coffea pseudozanguebariae, a wild caffeine-free coffee species, was determined. Two phenolic compounds were extracted from leaves, separated and characterized. Their structures were elucidated by mass spectrometry, and 1D and 2D NMR spectroscopy and were shown to be mangiferin (1) and isomangiferin (2), which were the main polyphenol products. Multiphoton fluorescence imaging was performed to visualize polyphenol distribution in leaf cross sections. Consistent biochemical analysis cell imaging techniques on leaves revealed yellow fluorescence in the epidermis and parenchyma cells corresponding to xanthone compounds.     

Determination of the enantiomeric excess of α-hydroxy acids

This work describes a convenient and accurate method for optical purity determination of α-hydroxy acids. Their derivatization with commercially available valine methyl ester affords diastereoisomers easily separable by HPLC using achiral C₁₈ columns.     

La détection infrarouge avec les plans focaux non refroidis : état de l'artUncooled focal plane infrared detectors: the state of the art

The emergence of uncooled detectors has opened new opportunities for IR detection for both military and commercial applications. Development of such devices involves a lot of trade-offs between the different parameters that define the technological stack. These trade-offs explain the number of different architectures that are under worldwide development. The key factor is to find a high sensitivity and low noise thermometer material compatible with silicon technology in order to achieve high thermal isolation in the smallest area as possible. Ferroelectric thermometer based hybrid technology and electrical resistive thermometer based (microbolometer) technology are under development. LETI and ULIS have chosen from the very beginning to develop first a monolithic microbolometer technology fully compatible with commercially available CMOS technology and secondly amorphous silicon based thermometer. This silicon approach has the greatest potential for reducing infrared detector manufacturing cost. After the development of the technology, the transfer to industrial facilities has been performed in a short period of time and the production is now ramping up with ULIS team in new facilities. LETI and ULIS are now working to facilitate the IRFPA integration into equipment in order to address a very large market. Achievement of this goal needs the development of smart sensors with on-chip advanced functions and the decrease of manufacturing cost of IRFPA by decreasing the pixel pitch and simplifying the vacuum package. We present in this paper the technology developed by CEA/LETI and its improvement for being able to designs 384×288 and 160×120 arrays with a pitch of 35 μm. Thermographic application needs high stability infrared detector with a precise determination of the amount of absorbed infrared flux. Hence, infrared detector with internal temperature stabilized shield has been developed and characterized. These results will be presented. To cite this article: J.-L. Tissot, C. R. Physique 4 (2003).     

k-intolerant capacities and Choquet integrals

We define an aggregation function to be (at most) k-intolerant if it is bounded from above by its kth lowest input value. Applying this definition to the discrete Choquet integral and its underlying capacity, we introduce the concept of k-intolerant capacities which, when varying k from 1 to n, cover all the possible capacities on n objects. Just as the concepts of k-additive capacities and p-symmetric capacities have been previously introduced essentially to overcome the problem of computational complexity of capacities, k-intolerant capacities are proposed here for the same purpose but also for dealing with intolerant or tolerant behaviors of aggregation. We also introduce axiomatically indices to appraise the extent to which a given capacity is k-intolerant and we apply them on a particular recruiting problem.     

Synthesis and characterization of polyethylene film grafted with acrylic acid and diethyleneglycol-dimethacrylate

Acrylic acid (AA) and diethyleneglycol-dimethacrylate (DEGDM) are grafted onto 25 μm low-density radio-peroxided polyethylene. Monomer content is determined by exchange capacity measurements. Studies of electrical resistance and zero-current membrane potential allow for the determination of the influence of DEGDM on both the dissociation of grafted AA and the permselectivity of these so-obtained cation-exchange membranes. DEGDM, acting as a crosslinking agent, limits the AA degree of grafting, slightly increases the electrical resistance, but contributes to enhance the permselectivity. For example, when these grafted films are immersed in 3M NaCl aqueous solutions, the addition of DEGDM leads to an increase of the transport number of Na⁺ close to 20%. © 1993 John Wiley & Sons, Inc.