Ratiometric Imaging Detection of Amyloid-β Fibrils by a Dual-Emissive Tris-Heteroleptic Ruthenium Complex.

Two dual fluorescent/phosphorescent tris-heteroleptic mononuclear Ru(ΙΙ) complexes ( and ) were designed and applied in amyloid-β (Aβ) sensing. These complexes have a general formula of Ru(phen)(dppz)(), where is (2-pyrazinyl)(2-pyridyl)(methyl)amine (H-) with different substituents (-OMe for , -H for ), phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Compared with the previously reported ratiometric probe with a di(pyrid-2-yl)(methyl)amine ligand, complex can be employed for not only ratiometric emissive detection of Aβ aggregation but also ratiometric imaging detection of Aβ fibrils. In ratiometric emissive detection, as the incubation time of the Aβ sample (Aβ and Aβ) was prolonged, a new phosphorescence emission band appeared with gradual enhancement of the emission intensity, while the fluorescence emission was basically unchanged, which could be treated as an intrinsic internal reference signal. In comparison, a larger ratiometric photoluminescence enhancement (/) was observed for Aβ aggregation with respect to Aβ. In ratiometric imaging detection, the imaging signals obtained from the phosphorescence emission are much brighter than the fluorescence emission in both Aβ and Aβ fibrils. As indicated by molecular docking results, stronger interactions were found between complex with Aβ fibrils, which included π/π, π/C-H, and π/H interactions between bidentate ligands dppz and phen with amino acid residues. Moreover, computational calculations were carried out to assist the interpretation of these experimental findings.