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 1-40 peptide. These complexes contained aromatic co-ligands to interact with the hydrophobic residues around the N-terminal domain of the Aβ 1-40 peptide, as well as solvato co-ligands to allow coordinative bond formation with histidine residues. We demonstrate that these complexes could inhibit Aβ 1-40 peptide aggregation in vitro, with potency superior to previous metal-based inhibitors reported. Furthermore, we have demonstrated the first example of luminescent detection of Aβ 1-40 peptides by transition metal complexes. © The Royal Society of Chemistry 2011.