Modeling Copper Binding to the Amyloid‑β Peptide at Different pH: Toward a Molecular Mechanism for Cu Reduction

Oxidative stress, including the production of reactive oxygen species (ROS), has been reported to be a key event in the etiology of Alzheimer’s disease (AD). Cu has been found in high concentrations in amyloid plaques, a hallmark of AD, where it is bound to the main constituent amyloid-β (Aβ) peptide. Whereas it has been proposed that Cu-Aβ complexes catalyze the production of ROS via redox-cycling between the Cu­(I) and Cu­(II) state, the redox chemistry of Cu-Aβ and the precise mechanism of redox reactions are still unclear. Because experiments indicate different coordination environments for Cu­(II) and Cu­(I), it is expected that the electron is not transferred between Cu-Aβ and reactants in a straightforward manner but involves structural rearrangement. In this work the structures indicated by experimental data are modeled at the level of modern density-functional theory approximations. Possible pathways for Cu­(II) reduction in different coordination sites are investigated by means of first-principles molecular dynamics simulations in the water solvent and at room temperature. The models of the ligand reorganization around Cu allow the proposal of a preferential mechanism for Cu-Aβ complex reduction at physiological pH. Models reveal that for efficient reduction the deprotonated amide N in the Ala 2-Glu 3 peptide bond has to be protonated and that interactions in the second coordination sphere make important contributions to the reductive pathway, in particular the interaction between COO^– and NH₂ groups of Asp 1. The proposed mechanism is an important step forward to a clear understanding of the redox chemistry of Cu-Aβ, a difficult task for spectroscopic approaches as the Cu-peptide interactions are weak and dynamical in nature

Tailoring Bimetallic Alloy Surface Properties by Kinetic Control of Self-Diffusion Processes at the Nanoscale

Achieving control of the nanoscale structure of binary alloys is of paramount importance for the design of novel materials with specific properties, leading to, for example, improved reaction rates and selectivity in catalysis, tailored magnetic behavior in electronics, and controlled growth of nanostructured materials such as graphene. By means of a combined experimental and theoretical approach, we show that the complex self-diffusion mechanisms determining these key properties can be mostly defined by kinetic rather than energetic effects. We explain how in the Ni–Cu system nanoscale control of self-diffusion and segregation processes close to the surface can be achieved by finely tuning the relative concentration of the alloy constituents. This allows tailoring the material functionality and provides a clear explanation of previously observed effects involved, for example, in the growth of graphene films and in the catalytic reduction of carbon dioxide

Steering the Chemistry of Carbon Oxides on a NiCu Catalyst

In the perspective of a sustainable energy economy, CO₂ reduction is attracting increasing attention as a key step toward the synthesis of fuels and valuable chemicals. A possible strategy to develop novel conversion catalysts consists in mimicking reaction centers available in nature, such as those in enzymes in which Fe, Ni, and Cu play a major role as active metals. In this respect, NiCu shows peculiar activity for both water-gas shift and methanol synthesis reactions. The identification of useful descriptors to engineer and tune the reactivity of a surface in the desired way is one of the main objectives of the science of catalysis, with evident applicative interest, as in this case. To this purpose, a crucial issue is the determination of the relevant active sites and rate-limiting steps. We show here that this approach can be exploited to design and tailor the catalytic activity and selectivity of a NiCu surface

Chemistry of the Methylamine Termination at a Gold Surface: From Autorecognition to Condensation

13The self-assembly of the naphthylmethylamine molecules (NMA) on the Au(111) surface is investigated by a combined experimental and theoretical approach. Three well-defined phases are observed upon different thermal treatments at the monolayer stage. The role played by the methylamine termination is evidenced in both the molecule–molecule and molecule–substrate interactions. The autorecognition process of the amino groups is identified as the driving factor for the formation of a complex hydrogen bonding scheme in small molecular clusters, possibly acting also as a precursor of a denitrogenation condensation process induced by thermal annealing.reservedmixedDri, Carlo; Fronzoni, Giovanna; Balducci, Gabriele; Furlan, Sara; Stener, Mauro; Feng, Zhijing; Comelli, Giovanni; Castellarin-Cudia, Carla; Cvetko, Dean; Kladnik, Gregor; Verdini, Alberto; Floreano, Luca; Cossaro, AlbanoDri, Carlo; Fronzoni, Giovanna; Balducci, Gabriele; Furlan, Sara; Stener, Mauro; Feng, Zhijing; Comelli, Giovanni; Castellarin Cudia, Carla; Cvetko, Dean; Kladnik, Gregor; Verdini, Alberto; Floreano, Luca; Cossaro, Alban