Group 9 metal-based inhibitors of β-amyloid (1–40) fibrillation as potential therapeutic agents for Alzheimer's disease

Abstract

We report here the first application of Group 9 metal complexes (i.e.iridium(III) and rhodium(III)) as inhibitors of amyloid fibrillogenesis and as luminescent probes for Aβ_1–40peptide. These complexes contained aromatic co-ligands to interact with the hydrophobic residues around the N-terminal domain of the Aβ_1–40peptide, as well as solvato co-ligands to allow coordinative bond formation with histidine residues. We demonstrate that these complexes could inhibit Aβ_1–40peptide aggregation in vitro, with potency superior to previous metal-based inhibitors reported. Furthermore, we have demonstrated the first example of luminescent detection of Aβ_1–40peptides by transition metal complexes.