| 1. |
- Chaudhary, Himanshu, et al.
(författare)
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Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases
- 2021
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:23, s. 26721-26734
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Tidskriftsartikel (refereegranskat)abstract
- 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, Nb10 and TiNb9, can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb10 or TiNb9 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 Nb10 and TiNb9 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 Kd 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.
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| 4. |
- Holmboe, Michael, et al.
(författare)
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Molecular Dynamics Simulations of Water and Sodium Diffusion in Smectite Interlayer Nanopores as a Function of Pore Size and Temperature
- 2014
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 118:2, s. 1001-1013
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Tidskriftsartikel (refereegranskat)abstract
- The diffusion coefficients (D) of water and solutes in nanoporous Na-smectite clay barriers have been widely studied because of their importance in high-level radioactive waste (HLRW) management and in the isolation of contaminated sites. However, few measurements have been carried out at the high temperatures that are expected to occur in HLRW repositories. We address this knowledge gap by using molecular dynamics (MD) simulations to predict the temperature dependence of diffusion in clay interlayer nanopores, expressed as a pore scale activation energy of diffusion (E-a). Our sensitivity analysis shows that accurate prediction of pore scale D and E-a values requires careful consideration of the influence of pore size, simulation cell size, and clay structure flexibility on MD simulation results. We find that predicted D values in clay interlayer nanopores are insensitive to the size of the simulation cell (contrary to the behavior observed in simulation of bulk liquid water) but sensitive to the vibrational motions of clay atoms (particularly in the smallest pores investigated here, the one-, two-, and three-layer hydrates). Our predicted D and E-a values are consistent with experimental data. They reveal, for both water and Na+, that E-a increases by similar to 6 kJ mol(-1) with increasing confinement, when going from bulk liquid water to the one-layer hydrate of Na-montmorillonite.
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| 5. |
- Rambaran, Mark, et al.
(författare)
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Polyoxoniobates as molecular building blocks in thin films
- 2021
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry. - 1477-9226 .- 1477-9234. ; 50:44, s. 16030-16038
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Tidskriftsartikel (refereegranskat)abstract
- Niobium oxide thin films have been prepared by spin-coating aqueous solutions of tetramethylammonium salts of the isostructural polyoxometalate clusters [Nb10O28]6−, [TiNb9O28]7− and [Ti2Nb8O28]8− onto silicon wafers, and annealing them. The [Nb10O28]6− cluster yields films of Nb2O5 in the orthorhombic and monoclinic crystal phases when annealed at 800 °C and 1000 °C, respectively, whereas the [TiNb9O28]7− and [Ti2Nb8O28]8− clusters yield the monoclinic crystal phases of Ti2Nb12O29 and TiNb2O7 (titanium–niobium oxides) in different ratios. We also demonstrate a protocol for depositing successive layers of metal oxide films. Finally, we explore factors affecting the roughness of the films.
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| 6. |
- Tinnacher, Ruth M., et al.
(författare)
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Ion adsorption and diffusion in smectite : Molecular, pore, and continuum scale views
- 2016
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533. ; 177, s. 130-149
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Tidskriftsartikel (refereegranskat)abstract
- Clay-rich media have been proposed as engineered barrier materials or host rocks for high level radioactive waste repositories in several countries. Hence, a detailed understanding of adsorption and diffusion in these materials is needed, not only for radioactive contaminants, but also for predominant earth metals, which can affect radionuclide speciation and diffusion. The prediction of adsorption and diffusion in clay-rich media, however, is complicated by the similarity between the width of clay nanopores and the thickness of the electrical double layer (EDL) at charged clay mineral-water interfaces. Because of this similarity, the distinction between 'bulk liquid' water and 'surface' water (i.e., EDL water) in clayey media can be ambiguous. Hence, the goal of this study was to examine the ability of existing pore scale conceptual models (single porosity models) to link molecular and macroscopic scale data on adsorption and diffusion in compacted smectite. Macroscopic scale measurements of the adsorption and diffusion of calcium, bromide, and tritiated water in Na-montmorillonite were modeled using a multi-component reactive transport approach while testing a variety of conceptual models of pore scale properties (adsorption and diffusion in individual pores). Molecular dynamics (MD) simulations were carried out under conditions similar to those of our macroscopic scale diffusion experiments to help constrain the pore scale models. Our results indicate that single porosity models cannot be simultaneously consistent with our MD simulation results and our macroscopic scale diffusion data. A dual porosity model, which allows for the existence of a significant fraction of bulk liquid water-even at conditions where the average pore width is only a few nanometers-may be required to describe both pore scale and macroscopic scale data.
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| 7. |
- Tournassat, Christophe, et al.
(författare)
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Molecular dynamics simulations of anion exclusion in clay interlayer nanopores
- 2016
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Ingår i: Clays and clay minerals. - 0009-8604 .- 1552-8367. ; 64:4, s. 374-388
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Tidskriftsartikel (refereegranskat)abstract
- The aqueous chemistry of water films confined between clay mineral surfaces remains an important unknown in predictions of radioelement migration from radioactive waste repositories. This issue is particularly important in the case of long-lived anionic radioisotopes (129I , 99TcO4 , 36Cl) which interact with clay minerals primarily by anion exclusion. For example, models of ion migration in clayey media do not agree as to whether anions are completely or partially excluded from clay interlayer nanopores. In the present study, this key issue was addressed for Cl using MD simulations for a range of nanopore widths (6 to 15 Å) overlapping the range of average pore widths that exists in engineered clay barriers. The MD simulation results were compared with the predictions of a thermodynamic model (Donnan Equilibrium model) and two pore-scale models based on the Poisson-Boltzmann equation under the assumption that interlayer water behaves as bulk liquid water. The simulations confirmed that anion exclusion from clay interlayers is greater than predicted by the pore-scale models, particularly at the smallest pore size examined. This greater anion exclusion stems from Cl being more weakly solvated in nano-confined water than it is in bulk liquid water. Anion exclusion predictions based on the PoissonBoltzmann equation were consistent with the MD simulation results, however, if the predictions included an ion closest approach distance to the clay mineral surface on the order of 2.0 0.8 Å. These findings suggest that clay interlayers approach a state of complete anion exclusion (hence, ideal semi-permeable membrane properties) at a pore width of 4.2 +/- 1.5 Å.
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