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

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 center dot radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the onformational Changes of the self-aggregation, of A beta with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrillsin the self-assembly of A beta(1-40) and globular structures in the short fragment A beta(15-21) in aqueous solution.