Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors

Here we report the discovery of tetracyclic benzothiazepines (BTZs) as highly potent and selective antimalarials along with the identification of the Plasmodium falciparum cytochrome bc₁ complex as the primary functional target of this novel compound class. Investigation of the structure activity relationship within this previously unexplored chemical scaffold has yielded inhibitors with low nanomolar activity. A combined approach employing genetically modified parasites, biochemical profiling, and resistance selection validated inhibition of cytochrome bc₁ activity, an essential component of the parasite respiratory chain and target of the widely used antimalarial drug atovaquone, as the mode of action of this novel compound class. Resistance to atovaquone is eroding the efficacy of this widely used antimalarial drug. Intriguingly, BTZ-based inhibitors retain activity against atovaquone resistant parasites, suggesting this chemical class may provide an alternative to atovaquone in combination therapy.     

Stability verification for monotone systems using homotopy algorithms

A monotone self-mapping of the nonnegative orthant induces a monotone discrete-time dynamical system which evolves on the same orthant. If with respect to this system the origin is attractive then there must exist points whose image under the monotone map is strictly smaller than the original point, in the component-wise partial ordering. Here it is shown how such points can be found numerically, leading to a recipe to compute order intervals that are contained in the region of attraction and where the monotone map acts essentially as a contraction. An important application is the numerical verification of so-called generalized small-gain conditions that appear in the stability theory of large-scale systems.     

High-power tandem pumped fiber amplifier with an output power of 2.9 kW

We report on a high power fiber amplifier tandem pumped by an industrial style thin-disk laser. An output power of 1 kW and a very good slope efficiency of 73% have been obtained for a state-of-the-art photonic crystal fiber originally designed for short-pulse amplification. We also compare this result to an experiment, where a power of 2.9 kW could be obtained from a step-index large-mode-area fiber with the same slope efficiency.     

Relations between edge lengths,dihedral and solid angles in tetrahedra

The tetrahedron, fundamental in organic chemistry, is examined in view of two important kinds of angles: to each tetrahedron edge belongs a dihedral angle (internal intersection angle between two faces having the edge as common side) and to each tetrahedron vertex a solid angle (area of the surface inside the tetrahedron on the unit sphere with the vertex as center). Based on preliminary lemmas, these angles are expressed in terms of edge lengths by an essential use of determinants. The resulting formulae enable to specify angle properties by edge lengths, especially with regard to equality and inequality of single solid angles or certain sums of dihedral angles. A special kind of equal solid angles leads to symmetry aspects. Finally, it is shown that by a particular rearrangement of edges in tetrahedra of a specific class some derived angle properties will be preserved.     

Hypervalent Iodine‐Catalyzed Oxidative Functionalizations Including Stereoselective Reactions

Hypervalent iodine chemistry is now a well‐established area of organic chemistry. Novel hypervalent iodine reagents have been introduced in many different transformations owing to their mild reaction conditions and environmentally friendly nature. Recently, these reagents have received particular attention because of their applications in catalysis. Numerous hypervalent iodine‐catalyzed oxidative functionalizations such as oxidations of various alcohols and phenols, α‐functionalizations of carbonyl compounds, cyclizations, and rearrangements have been developed successfully. In these catalytic reactions stoichiometric oxidants such as mCPBA or oxone play a crucial role to generate the iodine(III) or iodine(V) species in situ. In this Focus Review, recent developments of hypervalent iodine‐catalyzed reactions are described including some asymmetric variants. Catalytic reactions using recyclable hypervalent iodine catalysts are also covered.     

Silica colloidal crystals as three-dimensional scaffolds for supported lipid films

This report describes the assembly of laterally diffusive lipid layers within the pores of colloidal crystals for potential application in membrane-based sensing. The amount of lipid encapsulated within colloidal crystals depends upon the method used to introduce the lipid to the crystalline substrate. Relative to a planar supported lipid bilayer, lipid loading in a 6.6 microm thick crystal was 15-73 times greater, as observed by fluorescence microscopy. Protein adsorption studies indicate that the crystal pores are open and that the silica surface of the crystal is passivated with respect to adsorption of a model protein when coated with POPC. Furthermore, the mesoporous environment of the colloidal crystal is found to protect lipid films from drying and rehydration processes that destroy planar supported lipid bilayers. The potential of colloidal crystal encapsulated lipid films for chemical sensing is demonstrated by a model protein binding assay.     

Inter‐laboratory comparison: Quantitative surface analysis of thin Fe‐Ni alloy films

An international interlaboratory comparison of the measurement capabilities of four National Metrology Institutes (NMIs) and one Designated Institute (DI) in the determination of the chemical composition of thin Fe‐Ni alloy films was conducted via a key comparison (K‐67) of the Surface Analysis Working Group of the Consultative Committee for Amount of Substance. This comparison was made using XPS (four laboratories) and AES (one laboratory) measurements. The uncertainty budget of the measured chemical composition of a thin alloy film was dominated by the uncertainty of the certified composition of a reference specimen which had been determined by inductively coupled plasma mass spectrometry using the isotope dilution method. Pilot study P‐98 showed that the quantification using relative sensitivity factors (RSFs) of Fe and Ni derived from an alloy reference sample results in much more accurate result in comparison to an approach using RSFs derived from pure Fe and Ni films. The individual expanded uncertainties of the participants in the K‐67 comparison were found to be between 2.88 and 3.40 atomic %. The uncertainty of the key comparison reference value (KCRV) calculated from individual standard deviations and a coverage factor (k) of 2 was 1.23 atomic %. Copyright © 2011 John Wiley & Sons, Ltd.     

Cobalt(II)-catalyzed cross-coupling between polyfunctional arylcopper reagents and aryl fluorides or tosylates

[reaction: see text] Organocopper compounds prepared by the transmetalation of functionalized arylmagnesium halides with CuCN.2LiCl undergo smooth cross-coupling reactions with aryl fluorides and tosylates bearing a carbonyl function in the ortho position in the presence of Co(acac)(2) (7.5 mol %), Bu(4)NI (1 equiv), and 4-fluorostyrene (20 mol %) as promoters in DME/THF/DMPU leading to polyfunctional aromatics or heterocycles.     

Hybrid polymer/silica thermo-optic vertical coupler switches

Thermo-optic 1×2 vertical coupler switches (VCSs) using a hybrid polymer/silica integration technology were designed using a finite element method and a coupled mode method for different refractive index contrasts. The multilayer structures were optimized by thermal analysis. Based on these designs and simulations, hybrid polymer/silica thermo-optic 1×2 VCSs exhibiting low insertion loss, low crosstalk, low switching power and polarisation independence were demonstrated. Based on this building block, a 1×8 VCS has been fabricated. Received: 21 May 2001 / Published online: 23 October 2001