Classe de Ciências

info:eu-repo/semantics/publishedVersio

Is the largest aqueous gold cluster a superatom complex? Electronic structure & optical response of the structurally determined Au146(pMBA)57

The new water-soluble gold cluster Au146(pMBA)57, the structure of which has been recently determined at sub-atomic resolution by Vergara et al. [1], is the largest aqueous gold cluster ever structurally determined and likewise the smallest cluster with a stacking fault. The core presents a twinned truncated octahedron, while additional peripheral gold atoms follow a C2 rotational symmetry. According to the usual counting rules of the superatom complex (SAC) model, the compound attains a number of 92 SAC electrons if the overall net charge is 3- (three additional electrons). As this is the number of electrons required for a major shell closing, the question arises if Au146(pMBA)57 should be regarded as a superatom complex. Starting from the experimental coordinates we have analyzed the structure using density-functional theory. The optimized (relaxed) structure retains all the connectivity of the experimental coordinates, while removing much of its irregularities in interatomic distances, thereby enhancing the C2-symmetry feature. Analyzing the angular-momentum projected states, we show that, despite a small gap, the electronic structure does not exhibit SAC model character. In addition, optical absorption spectra are found to be relatively smooth compared to the example of the Au144(SR)60 cluster. The Au146(SR)57 cluster does not derive its stability from SAC character; it cannot be considered a superatom complex

Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer’s Disease

Alzheimer’s disease (AD) is a brain disorder that progressively undermines memory and thinking skills by affecting the hippocampus and entorhinal cortex. The main histopathological hallmarks of AD are the presence of abnormal protein aggregates (Aβ and tau), synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. However, oxidative stress or oxidative damage is also evident and commonly overlooked or considered a consequence of the advancement of dementia symptoms. The control or onset of oxidative stress is linked to the activity of the amyloid-β peptide, which may serve as both antioxidant and pro-oxidant molecules. Furthermore, oxidative stress is correlated with oxidative damage to proteins, nucleic acids, and lipids in vulnerable cell populations, which ultimately lead to neuronal death through different molecular mechanisms. By recognizing oxidative stress as an integral feature of AD, alternative therapeutic or preventive interventions are developed and tested as potential or complementary therapies for this devastating neurodegenerative disease

Molecular Docking and Aberration-Corrected STEM of Palladium Nanoparticles on Viral Templates

Viral templates are highly versatile biotemplates used for the synthesis of nanostructured materials. Rotavirus VP6 self-assembles into nanotubular hollow structures with well-defined diameters and variable lengths, serving as a nucleic acid-free biotemplate to synthesize metal nanoparticles of controlled size, shape, and orientation. Molecular docking simulations show that exposed residues (H173-S240-D242 and N200-N310) of VP6 have the ability to specifically bind Pd(II) ions, which serve as nucleation sites for the growth and stabilization of palladium nanoclusters. Using VP6 nanotubes as biotemplates allows for obtaining small Pd particles of 1–5 nm in diameter. Advanced electron microscopy imaging and characterization through ultra-high-resolution field-emission scanning electron microscopy (UHR-FE-SEM) and spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM) at a low voltage dose (80 kV) reveals, with high spatial resolution, the structure of Pd nanoparticles attached to the macromolecular biotemplates

Study of Methylene Blue Degradation by Gold Nanoparticles Synthesized within Natural Zeolites

We carried out the in situ synthesis of gold nanoparticles inside a natural clinoptilolite-type zeolite matrix, using ascorbic acid as reducing agent. The microstructure of both zeolite and zeolite-gold nanocomposite was characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Scanning Transmission Electron Microscopy (STEM), and Energy-Dispersive X-ray Spectroscopy (EDS) techniques. Size distribution as assessed by STEM indicated that 60% of gold nanoparticles measured less than 2.5 nm. Determination of the surface area by the BET method revealed a specific value of 27.35 m2/g. The catalytic activity of zeolite-gold regarding methylene blue degradation under different light-exposing conditions was evaluated by UV-Vis spectroscopy. The results indicated that 50% degradation was achieved in only 11 min in presence of sunlight. This reaction was faster in comparison with those obtained using a white LED light. A notable aspect of this study is that catalysis was carried out without the addition of any strong reducing agents, such as sodium borohydride (NaBH4)

High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer’s disease

Abnormal accumulation of brain metals is a key feature of Alzheimer’s disease (AD). Formation of amyloid-β plaque cores (APC) is related to interactions with biometals, especially Fe, Cu and Zn, but their particular structural associations and roles remain unclear. Using an integrative set of advanced transmission electron microscopy (TEM) techniques, including spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM), nano-beam electron diffraction, electron holography and analytical spectroscopy techniques (EDX and EELS), we demonstrate that Fe in APC is present as iron oxide (Fe3O4) magnetite nanoparticles. Here we show that Fe was accumulated primarily as nanostructured particles within APC, whereas Cu and Zn were distributed through the amyloid fibers. Remarkably, these highly organized crystalline magnetite nanostructures directly bound into fibrillar Aβ showed characteristic superparamagnetic responses with saturated magnetization with circular contours, as observed for the first time by off-axis electron holography of nanometer scale particles

Label-Free In Situ Chemical Characterization of Amyloid Plaques in Human Brain Tissues

The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer’s disease. Altered metabolism of essential biometals is another feature of Alzheimer’s, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date. A better understanding of amyloid plaque composition and the role of the metals associated with them is critical. To establish this knowledge, the ability to resolve chemical variations at nanometer length scales relevant to biology is essential. Here, we present a methodology for the label-free, nanoscale chemical characterization of amyloid plaques within human Alzheimer’s disease tissue using synchrotron X-ray spectromicroscopy. Our approach exploits a C–H carbon absorption feature, consistent with the presence of lipids, to visualize amyloid plaques selectively against the tissue background, allowing chemical analysis to be performed without the addition of amyloid dyes that alter the native sample chemistry. Using this approach, we show that amyloid plaques contain elevated levels of calcium, carbonates, and iron compared to the surrounding brain tissue. Chemical analysis of iron within plaques revealed the presence of chemically reduced, low-oxidation-state phases, including ferromagnetic metallic iron. The zero-oxidation state of ferromagnetic iron determines its high chemical reactivity and so may contribute to the redox burden in the Alzheimer’s brain and thus drive neurodegeneration. Ferromagnetic metallic iron has no established physiological function in the brain and may represent a target for therapies designed to lower redox burdens in Alzheimer’s disease. Additionally, ferromagnetic metallic iron has magnetic properties that are distinct from the iron oxide forms predominant in tissue, which might be exploitable for the in vivo detection of amyloid pathologies using magnetically sensitive imaging. We anticipate that this label-free X-ray imaging approach will provide further insights into the chemical composition of amyloid plaques, facilitating better understanding of how plaques influence the course of Alzheimer’s disease

The ionophore thiomaltol induces rapid lysosomal accumulation of copper and apoptosis in melanoma.

In this report, we investigate the toxicity of the ionophore thiomaltol (Htma) and Cu salts to melanoma. Divalent metal complexes of thiomaltol display toxicity against A375 melanoma cell culture resulting in a distinct apoptotic response at submicromolar concentrations, with toxicity of Cu(tma)2 > Zn(tma)2 >> Ni(tma)2. In metal-chelated media, Htma treatment shows little toxicity, but the combination with supplemental CuCl2, termed Cu/Htma treatment, results in toxicity that increases with suprastoichiometric concentrations of CuCl2 and correlates with the accumulation of intracellular copper. Electron microscopy and confocal laser scanning microscopy of Cu/Htma treated cells shows a rapid accumulation of copper within lysosomes over the course of hours, concurrent with the onset of apoptosis. A buildup of ubiquitinated proteins due to proteasome inhibition is seen on the same timescale and correlates with increases of copper without additional Htma

MicroED Structure of Au 146 (p-MBA) 57 at Subatomic Resolution Reveals a Twinned FCC Cluster

International audienceSolving the atomic structure of metallic clusters is fundamental to understanding their optical, electronic, and chemical properties. Herein we present the structure of the largest aqueous gold cluster, Au 146 (p-MBA) 57 (p-MBA: para-mercaptobenzoic acid), solved by electron diffraction (MicroED) to subatomic resolution (0.85 Å) and by X-ray diffraction at atomic resolution (1.3 Å). The 146 gold atoms may be decomposed into two constituent sets consisting of 119 core and 27 peripheral atoms. The core atoms are organized in a twinned FCC structure whereas the surface gold atoms follow a C 2 rotational symmetry about an axis bisecting the twinning plane. The protective layer of 57 p-MBAs fully encloses the cluster and comprises bridging, monomeric, and dimeric staple motifs. Au 146 (p-MBA) 57 is the largest cluster observed exhibiting a bulk-like FCC structure as well as the smallest gold particle exhibiting a stacking fault