The Multivalent Effect in Glycosidase Inhibition: Probing the Influence of Valency,Peripheral Ligand Structure,and Topology with Cyclodextrin‐Based Iminosugar Click Clusters

In view of recent reports of a strong multivalent effect in glycosidase inhibition, a library of β‐CD‐based multivalent iminosugars has been efficiently synthesized by way of Cu^I‐catalyzed azide–alkyne cycloaddition (CuAAC). In combination with the first application of isothermal titration calorimetry (ITC) experiments to the study of multivalent iminosugar–enzyme interactions, the inhibition properties of these click clusters were evaluated on a panel of glycosidases. The structural parameters that were varied include valency, peripheral ligand structure, and topology. The inhibition results obtained with the iminosugar clusters further highlight the importance of multivalency in the inhibition of α‐mannosidase. Generally, the evaluated multivalent iminosugars displayed comparable thermodynamic signatures of binding towards α‐mannosidase (Jack bean): that is, large negative enthalpies of complexation coupled with small entropies of either sign. In addition, the enthalpy–entropy compensation observed in all tested cases may be attributed to a common mechanism of dissociation for the enzyme–multivalent iminosugar interactions. The measured binding stoichiometries indicated that each iminosugar cluster interacts with no more than one protein molecule.     

The synthesis and characterization of copper-based metal–organic framework/graphite oxide composites

New composites of a copper-based metal–organic framework and graphite oxide were synthesized with different ratios of HKUST-1 (also called MOF-199) and graphite oxide. These compounds, as well as the parent materials, were characterized by X-ray diffraction, sorption of nitrogen, FT-IR spectroscopy, thermal analyses, scanning electron microscopy, and sorption of hydrogen. The composites exhibit features similar to HKUST-1 as well as an increased porosity compared to the parent materials. The formation of new small pores is demonstrated by an increase in the hydrogen uptake. The results suggest that the building process of the composites occurs via the reaction/binding of the copper dimers from the HKUST-1 with/to the functional groups in graphite oxide (epoxy, carboxylic, hydroxylic, sulfonic).     

1H-NMR study of maleic anhydride modified ethylene-diene copolymers

An alternative route for the preparation of polar polyolefins involving “site specific” functionalisation is presented. In this approach, the functionalisation of polyethylene is achieved by the combination of two well known processes: the copolymerization of ethylene with a non conjugated diene, followed by the reaction of the copolymer with maleic anhydride (MAH) via Alder Ene reaction. This route avoids the use of peroxides and consequently limits degradation and other undesirable reactions such as chain scission, crosslinking and coupling, usually occurring under free radical conditions. The molecular structure of the MAH modified ethylene-diene copolymer is investigated by spectroscopic techniques, such as FTIR and ¹H-NMR, applied to the modified copolymer as well to model compounds and copolymers. The spectroscopic studies confirm that the functionalisation of the ethylene/5,7-dimethyl-1,6-diene (EDMO) copolymer proceeds mainly through the Alder Ene mechanism, under our experimental conditions, and provide data to elucidate the molecular structure of the modified MAH copolymer.