Ruthenium Complexes Double-Vex Alzheimer’s Peptide

Peering inside the brain of a person with Alzheimer’s disease reveals cobwebs of disruptive fibrils made up of aggregated amyloid-β peptide. Some scientists believe the key to treating Alzheimer’s, or even preventing it, is to design molecular probes for real-time monitoring of amyloid-β and to develop drug treatments that block amyloid-β aggregation. In a new development, a team led by Angel A. Martí of Rice University and Rajeev Prabhakar of the University of Miami has uncovered that ruthenium complexes containing bulky aromatic bipyridine and dipyridophenazine ligands can perform both functions. The ruthenium complexes, which are already used in DNA detection, luminesce when they bind amyloid-β, and the researchers propose that their bulk could inhibit aggregate formation (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja404850u). Using experimental and computational techniques, the researchers found that the ruthenium complexes bind to amyloid-β with the bulky ligands aligning parallel to the fibril axis. They note that the parallel binding is unprecedented for the ruthenium complexes, which align perpendicular to the axis of DNA strands. The parallel binding orientation, the researchers believe, could block amyloid aggregation. The finding opens new possibilities for using molecules with extended aromatic systems as agents to tackle Alzheimer’s, they conclude.