This study explores the interactions of the cis-[Ru(phen)₂(Apy)₂]²⁺ complex (RuApy, phen = 1,10-phenanthroline, Apy = 3,4-aminopyridine) with model lipid membranes to explain the role this complex plays in mitigating Aβ toxicity in PC12 neuronal cells. Fluorescence quenching, surface pressure isotherms in Langmuir monolayers, and infrared reflection–absorption analyses revealed that the positively charged RuApy interacts with the phosphate headgroups of monolayers, indirectly affecting ester carbonyl groups through hydrogen bonding with the amino group of the pyridine ligand of RuApy. These results offer a scenario for the protective effect of RuApy against Aβ toxicity in neuronal cells in which these interactions shield the electrostatic interactions of Aβ with lipid membranes, preserving membrane integrity and mitigating the deleterious influence of Aβ. This opens new avenues for antiamyloid strategies, focusing on compounds that prevent salt-bridge formation between bilayer membranes and amyloid proteins, aiding in the rational design of effective antiamyloid agents for therapeutic application.

中文翻译：

---

顺式-[Ru（phen）2（3,4Apy）2]2+ 与模型脂质膜的结合：对抗淀粉样蛋白药物开发新工具的影响


本研究探讨了顺式-[Ru（phen）₂（Apy）₂^]2+ 复合物 （RuApy，phen = 1,10-菲咯啉，Apy = 3,4-氨基吡啶） 与模型脂质膜的相互作用，以解释该复合物在减轻 PC12 神经元细胞中 Aβ 毒性中的作用。荧光猝灭、Langmuir 单层中的表面压力等温线和红外反射-吸收分析表明，带正电荷的 RuApy 与单层的磷酸盐头基相互作用，通过与 RuApy 的吡啶配体的氨基的氢键间接影响酯羰基。这些结果为 RuApy 对神经元细胞中 Aβ 毒性的保护作用提供了一种情景，其中这些相互作用屏蔽了 Aβ 与脂质膜的静电相互作用，保持了膜的完整性并减轻了 Aβ 的有害影响。这为抗淀粉样蛋白策略开辟了新的途径，专注于防止双层膜和淀粉样蛋白之间形成盐桥的化合物，有助于合理设计用于治疗应用的有效抗淀粉样蛋白药物。