No abstract

Microwave preparation of polyoxoniobates and -tantalates afford a more rapid alternative to conventional hydrothermal methods of synthesis, in addition to allowing for the use of anhydrous niobium pentoxide in lieu of niobic acid, [a]

Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency in amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb 10 and TiNb 9 , can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb 10 or TiNb 9 reduces the S100A9 amyloid formation rate and amyloid quantity. Atomic force microscopy imaging demonstrated the complete absence of long S100A9 amyloid fibrils at increasing concentrations of either POM and the presence of only round-shaped and slightly elongated aggregates. Molecular dynamics simulation revealed that both Nb 10 and TiNb 9 bind to native S100A9 homo-dimer by forming ionic interactions with the positively charged Lys residue-rich patches on the protein surface. The acrylamide quenching of intrinsic fluorescence showed that POM binding does not perturb the Trp 88 environment. The far and near UV circular dichroism revealed no large-scale perturbation of S100A9 secondary and tertiary structures upon POM binding. These indicate that POM binding involves only local conformational changes in the binding sites. By using intrinsic and 8-anilino-1-naphthalene sulfonate fluorescence titration experiments, we found that POMs bind to S100A9 with a K d of ca. 2.5 μM. We suggest that the region, including Lys 50 to Lys 54 and characterized by high amyloid propensity, could be the key sequences involved in S1009 amyloid self-assembly. The inhibition and complete hindering of S100A9 amyloid pathways may be used in the therapeutic applications targeting the amyloid-neuroinflammatory cascade in neurodegenerative diseases.

Polyoxometalates (POMs), ranging in size from 1 to 10's of nanometers, resemble building blocks of inorganic materials. Elucidating their complex solubility behavior with alkali-counterions can inform natural and synthetic aqueous processes. In the study of POMs ([Nb 24 O 72 H 9 ] 15À , Nb 24 ) we discovered an unusual solubility trend (termed anomalous solubility) of alkali-POMs, in which Nb 24 is most soluble with the smallest (Li + ) and largest (Rb/Cs + ) alkalis, and least soluble with Na/K + . Via computation, we define a descriptor (σprofile) and use an artificial neural network (ANN) to predict all three described alkali-anion solubility trends: amphoteric, normal

A polycondensation reaction of the orthotungstate anion WO 4 2– , buffered at pH 7.5 in a TRIS-HCl (0.15 M) solution, results in the first example of a discrete polyoxotungstate anion, with just two W ions stabilized with TRIS ligands. It was isolated and characterized as Na 2 [W VI 2 O 6 (C 4 O 3 NH 10 ) 2 ]·6H 2 O by single-crystal and powder X-ray diffraction, FT-IR spectroscopy, thermogravimetrical analysis (TGA), and elemental analysis in solid state and by electro-spray ionization mass spectrometry (ESI-MS), 13 C, and 183 W NMR, as well as Raman spectroscopy in solution. This synthesis demonstrates the crucial and new role of the added tris-alkoxy ligand in the development of a new hybrid TRIS-isopolytungstate with the lowest known nuclearity (so far) and the terminal oxygens substituted with two nitrogen atoms arising from amines of the TRIS ligands.