Cationic Geminoid Peptide Amphiphiles Inhibit DENV2 Protease,Furin, and Viral Replication

Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (C₁₅H₃₁C(O)-Lys-(Gly or Ala)_nLys-NHC₁₆H₃₃, shorthand notation C₁₆-KX_nK-C₁₆ with X = A or G, and n = 0–2). The representatives with 1 or 2 Ala inhibit dengue protease and human furin, two serine proteases involved in dengue virus infection that have peptides with cationic amino acids as their preferred substrates, with IC₅₀ values in the lower µM range. The geminoid C₁₆-KAK-C₁₆ combined inhibition of DENV2 protease (IC₅₀ 2.3 µM) with efficacy against replication of wildtype DENV2 in LLC-MK2 cells (EC₅₀ 4.1 µM) and an absence of toxicity. We conclude that the lysine-based geminoids have activity against dengue virus infection, which is based on their inhibition of the proteases involved in viral replication and are therefore promising leads to further developing antiviral therapeutics, not limited to dengue.     

Evolution of the active species of homogeneous Ru hydrodeoxygenation catalysts in ionic liquids

This work establishes structure–property relationships in Ru-based catalytic systems for selective hydrodeoxygenation of ketones to alkenes by combining extensive catalytic testing, in situ X-ray absorption spectroscopy (XAS) under high pressures and temperatures and ex situ XAS structural characterization supported by density functional theory (DFT) calculations. Catalytic tests revealed the difference in hydrogenation selectivity for ketones (exemplified by acetone) or alkenes (exemplified by propene) upon changing the reaction conditions, more specifically in the presence of CO during a pretreatment step. XAS data demonstrated the evolution of the local ruthenium structure with different amounts of Cl/Br and CO ligands. In addition, in the absence of CO, the catalyst was reduced to Ru⁰, and this was associated with a significant decrease of the selectivity for ketone hydrogenation. For the Ru–bromide carbonyl complex, selectivity towards acetone hydrogenation over propene hydrogenation was explained on the basis of different relative energies of the first intermediate states of each reaction. These results give a complete understanding of the evolution of the Ru species, used for the catalytic valorization of biobased polyols to olefins in ionic liquids, identifying the undesired deactivation routes as well as possibilities for reactivation.

This work establishes structure–property relationships in Ru-based catalytic systems for the selective hydrodeoxygenation of ketones to alkenes.     

Verbessertes Verfahren Strychnin aus dem Mageninhalte, Speisen u. s. w. in gerichtlichen F?llen abzuscheiden

Ohne ZusammenfassungAus dem Holländischen übertragen von der Redaction.     

Electrochemically-Switched 2nd Order Non-Linear Optical Response in an Arylimido-Polyoxometalate with High Contrast and Cyclability

Electrochemically switched 2^nd order non-linear optical responses have been demonstrated for the first time in polyoxometalates (POMs), with an arylimido-derivative showing a leading combination of high on/off contrast (94 %), high visible transparency, and cyclability. Spectro-electrochemical and TD-DFT studies indicate that the switch-off results from weakened charge transfer (CT) character of the electronic transitions in the reduced state. This represents the first study of an imido-POM reduced state, and demonstrates the potential of POM hybrids as electrochemically activated molecular switches.