The primitive spectrum of a semigroup of Markov operators

Positivity - For a semigroup $$\mathcal {S}$$ of Markov operators on a space of continuous functions, we use $$\mathcal {S}$$-invariant ideals to describe qualitative properties of $$\mathcal {S}$$...     

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.     

To Sandwich Technetium: Highly Functionalized Bis-Arene Complexes [99mTc(η6-arene)2]+ Directly from Water and [99mTcO4]−

The labeling of (bio)molecules with metallic radionuclides such as ^99mTc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis-arene sandwich complexes are generally prepared by the Fischer–Hafner reaction. In extension of this, we show that [^99mTc(η⁶-C₆R₆)₂]⁺-type complexes are directly accessible from water and [^99mTcO₄]⁻, even using arenes incompatible with Fischer–Hafner conditions. To unambiguously confirm the nature of these unprecedented ^99mTc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η⁶-C₁₀H₈)₂]⁺ with the corresponding phenyl groups. The ease with which highly stable [^99mTc(η⁶-C₆R₆)₂]⁺ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures.     

Microporous Molecular Materials from Dipeptides Containing Non‐proteinogenic Residues

Dipeptides with two hydrophobic side chains have proved to be an exceptional source of microporous organic materials, but since previous structures were limited to the incorporation of only proteinogenic residues, their full potential as adsorbents has remained unexplored. Single‐crystal XRD data for ten new compounds with non‐proteinogenic L ‐2‐aminobutanoic acid and/or L ‐2‐amino‐pentanoic acid are presented. The gas‐phase accessibility of their crystal pores, with cross‐sections of 2.3 to 5.1 Å, was monitored by CO₂ and CH₄ adsorption isotherms. Included CO₂ was also detected spectroscopically by 2D MAS NMR. An extensive conformational analysis reveals that the use of linear rather than branched side chains (such as L ‐valine and L ‐isoleucine) affords peptides with a greater degree of conformational freedom and yields more‐flexible channel surfaces that may easily adapt to a series of potential guest molecules.     

Fully printed flexible audio system on the basis of low‐voltage polymeric organic field effect transistors with three layer dielectric

Fully mass printed, flexible and truly polymeric organic field effect transistors consisting of a three layer dielectric made of CYTOP (low‐k), PVA (intermediate) and P(VDF‐TrFE‐CTFE)(high‐k) are introduced. Gravure‐, flexo‐and screen printing were selected as highly productive manufacturing technologies. These OFETs work at strongly reduced voltages and show high field effect mobility (µ = 0.2 cm²/Vs) and remarkable good bias stress stability at very high current density (50 µA/mm). Fully printed OFETs are used for the realization of ring oscillators working in the kHz regime at reduced supply voltage (10 V). In combination with printed fully polymeric piezoelectric loudspeakers, this work shows for the first time fully printed flexible audio systems. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1409–1415     

Well‐Defined Palladium Nanoparticles Supported on Siliceous Mesocellular Foam as Heterogeneous Catalysts for the Oxidation of Water

Herein, we describe the use of Pd nanoparticles immobilized on an amino‐functionalized siliceous mesocellular foam for the catalytic oxidation of H₂O. The Pd nanocatalyst proved to be capable of mediating the four‐electron oxidation of H₂O to O₂, both chemically and photochemically. The Pd nanocatalyst is easy to prepare and shows high chemical stability, low leaching, and recyclability. Together with its promising catalytic activity, these features make the Pd nanocatalyst of potential interest for future sustainable solar‐fuel production.