Light-Induced Disassembly β-Amyloid Aggregates by Ruthenium Complex

Abstract

Ruthenium (II) complexes are visible light-active photocatalyst extensively used for solar energy harvesting and conversion applications. Here, we report our finding that tris(2,2-bipyridine) ruthenium(II) $[Ru(bpy)_3^{2+}]$ can function as a highly sensitive, biocompatible agent for anti-amyloidgenesis. The abnormal aggregation of β-amyloid (Aβ) peptides is a major pathological hallmark of Alzheimer's disease. According to our multiple analyses, visible light-induced $Ru(bpy)_3^{2+}$ successfully disassembles preformed Aβ aggregates into non-fibrillar aggregates by destructing β-sheet structures. Moreover, we identified the changes of solubility and diameter of the disassembled A？ aggregates and photo-degradation of small oligomers including trimeric, tetrameric species. We also validated that photoexcited $Ru(bpy)_3^{2+}$ can cleave peptide bonds in Aβ using mass spectroscopy. The efficacy of $Ru(bpy)_3^{2+}$ is derived from photon-energy in visible spectrum. $Ru(bpy)_3^{2+}$ generates reactive oxygen species such as singlet oxygen upon absorbing photon energy (λ= 452 nm), resulting in disassembly of Aβ aggregates. Furthermore, photoexcited $Ru(bpy)_3^{2+}$ can reduce in vitro cytotoxicity of Aβ aggregates. Our study advances a new insight of ruthenium (II) complexes as therapeutic agents against AD.