Acetylcholinesterase and Aβ Aggregation Inhibition by Heterometallic Ruthenium(II)–Platinum(II) Polypyridyl Complexes

Abstract

Two heteronuclear ruthenium(II)-platinum(II) complexes [Ru(bpy)₂(BPIMBp)PtCl₂]²⁺ (3) and [Ru(phen)₂(BPIMBp)PtCl₂]²⁺ (4), where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and BPIMBp = 1,4'-bis[(2-pyridin-2-yl)-1H-imidazol-1-ylmethyl]-1,1'-biphenyl, have been designed and synthesized from their mononuclear precursors [Ru(bpy)₂(BPIMBp)]²⁺ (1) and [Ru(phen)₂(BPIMBp)]²⁺ (2) as multitarget molecules for Alzheimer's disease (AD). The inclusion of the cis-PtCl₂ moiety facilitates the covalent interaction of Ru(II) polypyridyl complexes with amyloid β (Aβ) peptide. These multifunctional complexes act as inhibitors of acetylcholinesterase (AChE), Aβ aggregation, and Cu-induced oxidative stress and protect neuronal cells against Aβ-toxicity. The study highlights the design of metal based anti-Alzheimer's disease (AD) systems.