ABSTRACT
Water-soluble polymers with the ability to complex metal ions through complexing ligands have attracted significant interest in diverse domains, such as optical or catalyst applications. In this paper, we successfully synthesized, through a one-pot process combining polymerization-induced self-assembly and reversible addition-fragmentation chain transfer polymerization, aqueous dispersions of terpyridine-decorated poly[poly(ethylene glycol)methyl ether methacrylate]-b-poly(methyl methacrylate) (tpy-PPEGMA-b-PMMA) amphiphilic block copolymers. The in-situ formation of well-defined amphiphilic block copolymers and their self-assembly led to nanosphere latex with the hydrodynamic diameters increasing from 17 to 52 nm and the length of the copolymers increasing from 21,000 to 51,000 g·mol-1. These aqueous dispersed tpy-PPEGMA-b-PMMA nanospheres effectively complex metal ions, such as Cu2+, in a stoichiometric ratio of 2:1. Subsequently, these metal-complexed nanospheres were employed as soft template nanocarriers to control, on the nanometer scale, the dispersion of metal on a nanostructured support. This is exemplified by the synthesis of copper supported on cerium oxide hollow spheres (Cu-CeO2) using Cu2+-tpy-PPEGMA-b-PMMA as template nanocarriers and CeO2 nanoparticles. This novel assembly engineering strategy for the preparation of atomically dispersed metal on a nanostructured support was highlighted through the utilization of Cu-CeO2 hollow spheres as an electrocatalyst for the nitrate reduction reaction (NO3RR) to NH3. These encouraging outcomes emphasize the potential of metal-metal oxide-nanostructured materials to treat contaminated water sources with nitrate while allowing the green production of ammonia.
ABSTRACT
Aspergillus fumigatus is a saprophytic fungus and opportunistic pathogen often causing fatal infections in immunocompromised patients. Recently AfKDNAse, an exoglycosidase hydrolyzing 3-deoxy-D-galacto-D-glycero-nonulosonic acid (KDN), a rare sugar from the sialic acid family, was identified and characterized. The principal function of AfKDNAse is still unclear, but a study suggests a critical role in fungal cell wall morphology and virulence. Potent AfKDNAse inhibitors are required to better probe the enzyme's biological role and as potential antivirulence factors. In this work, we developed a set of AfKDNAse inhibitors based on enzymatically stable thio-KDN motifs. C2, C9-linked heterodi-KDN were designed to fit into unusually close KDN sugar binding pockets in the protein. A polymeric compound with an average of 54 KDN motifs was also designed by click chemistry. Inhibitory assays performed on recombinant AfKDNAse showed a moderate and strong enzymatic inhibition for the two classes of compounds, respectively. The poly-KDN showed more than a nine hundred fold improved inhibitory activity (IC50 = 1.52 ± 0.37 µM, 17-fold in a KDN molar basis) compared to a monovalent KDN reference, and is to our knowledge, the best synthetic inhibitor described for a KDNase. Multivalency appears to be a relevant strategy for the design of potent KDNase inhibitors. Importantly, poly-KDN was shown to strongly decrease filamentation when co-cultured with A. fumigatus at micromolar concentrations, opening interesting perspectives in the development of antivirulence factors.