We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
On the generation of OH radical species from HO by Cu(I) amyloid beta peptide model complexes: a DFT investigation.
- Authors
Prosdocimi, Tommaso; Gioia, Luca; Zampella, Giuseppe; Bertini, Luca
- Abstract
According to different studies, the interaction between amyloid β-peptide (Aβ) and copper ions could yield radical oxygen species production, in particular the highly toxic hydroxyl radical OH that is suspected to contribute to Alzheimer's disease pathogenesis. Despite intensive experimental and computational studies, the nature of the interaction between copper and Aβ peptide, as well as the redox reactivity of the system, are still matter of debate. It was proposed that in Cu(II) → Cu(I) reduction the complex Cu(II)-Aβ could follow a multi-step conformational change with redox active intermediates that may be responsible for OH radical production from HO through a Fenton-like process. The purpose of this work is to evaluate, using ab initio Density Functional Theory computations, the reactivity of different Cu(I)-Aβ coordination modes proposed in the literature, in terms of OH production. For each coordination model, we considered the corresponding HO adduct and performed a potential energy surface scan along the reaction coordinate of O-O bond dissociation of the peroxide, resulting in the production of OH radical, obtaining reaction profiles for the evaluation of the energetic of the process. This procedure allowed us to confirm the hypothesis according to which the most populated Cu(I)-Aβ two-histidine coordination is not able to perform efficiently HO reduction, while a less populated three-coordinated form would be responsible for the OH production. We show that coordination modes featuring a third nitrogen containing electron-donor ligand (an imidazole ring of an histidine residue is slightly favored over the N-terminal amine group) are more active towards HO reduction.
- Subjects
METAL complexes; COPPER compounds; DENSITY functional theory; HYDROXYL group; COORDINATION compounds; AMYLOID beta-protein
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2016, Vol 21, Issue 2, p197
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-015-1322-y