Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of Aβ Self-Aggregation and Therapeutic Applications in Alzheimer’s Disease

Abstract

The complexes cis-[Ru(phen)₂(Apy)₂]²⁺, Apy = 4-aminopyridine and 3,4-aminopyridine, are stable in aqueous solution with strong visible absorption. They present emission in the visible region with long lifetime that accumulates in the cytoplasm of Neuro2A cell line without appreciable cytotoxicity. The complexes also serve as mixed-type reversible inhibitors of human AChE and BuChE with high active site contact. cis-[Ru(phen)₂(3,4Apy)₂]²⁺ competes efficiently with DMPO by the OH^• radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the conformational changes of the self-aggregation of Aβ with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrills in the self-assembly of Aβ_1-40 and globular structures in the short fragment Aβ_15-21 in aqueous solution.