Binding of <i>cis</i>-[Ru(phen)<sub>2</sub>(3,4Apy)<sub>2</sub>]<sup>2+</sup> to Model Lipid Membranes: Implications\nfor New Tools in the Development of Antiamyloid Drugs

This study explores\nthe interactions of the <i>cis</i>-[Ru(phen)<sub>2</sub>(Apy)<sub>2</sub>]<sup>2+</sup> complex (RuApy,\nphen = 1,10-phenanthroline, Apy = 3,4-aminopyridine) with model lipid\nmembranes to explain the role this complex plays in mitigating Aβ\ntoxicity in PC12 neuronal cells. Fluorescence quenching, surface pressure\nisotherms in Langmuir monolayers, and infrared reflection–absorption\nanalyses revealed that the positively charged RuApy interacts with\nthe phosphate headgroups of monolayers, indirectly affecting ester\ncarbonyl groups through hydrogen bonding with the amino group of the\npyridine ligand of RuApy. These results offer a scenario for the protective\neffect of RuApy against Aβ toxicity in neuronal cells in which\nthese interactions shield the electrostatic interactions of Aβ\nwith lipid membranes, preserving membrane integrity and mitigating\nthe deleterious influence of Aβ. This opens new avenues for\nantiamyloid strategies, focusing on compounds that prevent salt-bridge\nformation between bilayer membranes and amyloid proteins, aiding in\nthe rational design of effective antiamyloid agents for therapeutic\napplication.