Ruthenium(II)-Arene Complexes with a 2,2'-Bipyridine Ligand as Anti-Aβ Agents

Agents that target the amyloid-β (Aβ) peptide associated with Alzheimer's disease have seen renewed interest following the clinical success of antibody therapeutics. Small molecules, specifically metal-based complexes, are excellent candidates for advancement, given their relative ease of preparation and modular scaffold. Herein, several ruthenium-arene complexes containing 2,2-bipyridine (bpy) ligands were prepared and evaluated for their respective ability to modulate the aggregation of Aβ. This was carried out using the three sequential methods of thioflavin T (ThT) fluorescence, dynamic ligand scattering (DLS), and transmission electron microscopy (TEM). Overall, it was observed that RuBA, the complex with a 4,4-diamino-2,2-bipyridine ligand, had the greatest impact on Aβ aggregation. Further evaluation of the complexes was performed to determine their relative affinity for serum albumin and biocompatibility towards two neuronal cell lines. Ultimately, RuBA outperformed the other Ru complexes, where the structure-activity relationship codified the importance of the amino groups on the bpy for anti-Aβ activity.