Ruokonen Suvi-Katriina, Sanwald Corinna, Robciuc Alexandra, Hietala Sami, Rantamäki Antti H, Witos Joanna, King Alistair W T, Lämmerhofer Michael, Wiedmer Susanne K
Department of Chemistry, Faculty of Science, University of Helsinki, A.I. Virtasen aukio 1, 00560, Helsinki, Finland.
Institute of Pharmaceutical Sciences, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.
Chemistry. 2018 Feb 21;24(11):2669-2680. doi: 10.1002/chem.201704924. Epub 2018 Jan 24.
This study aims at extending the understanding of the toxicity mechanism of ionic liquids (ILs) using various analytical methods and cytotoxicity assays. The cytotoxicity of eight ILs and one zwitterionic compound was determined using mammalian and bacterial cells. The time dependency of the IL toxicity was assessed using human corneal epithelial cells. Hemolysis was performed using human red blood cells and the results were compared with destabilization data of synthetic liposomes upon addition of ILs. The effect of the ILs on the size and zeta potential of liposomes revealed information on changes in the lipid bilayer. Differential scanning calorimetry was used to study the penetration of the ILs into the lipid bilayer. Pulsed field gradient nuclear magnetic resonance spectroscopy was used to determine whether the ILs occurred as unimers, micelles, or if they were bound to liposomes. The results show that the investigated ILs can be divided into three groups based on the cytotoxicity mechanism: cell wall disrupting ILs, ILs exerting toxicity through both cell wall penetration and metabolic alteration, and ILs affecting solely on cell metabolism.
本研究旨在通过各种分析方法和细胞毒性测定，扩展对离子液体（ILs）毒性机制的理解。使用哺乳动物细胞和细菌细胞测定了八种离子液体和一种两性离子化合物的细胞毒性。使用人角膜上皮细胞评估了离子液体毒性的时间依赖性。使用人红细胞进行溶血实验，并将结果与添加离子液体后合成脂质体的去稳定化数据进行比较。离子液体对脂质体大小和zeta电位的影响揭示了脂质双层变化的信息。差示扫描量热法用于研究离子液体对脂质双层的渗透。脉冲场梯度核磁共振光谱法用于确定离子液体是以单聚体、胶束形式存在，还是与脂质体结合。结果表明，根据细胞毒性机制，所研究的离子液体可分为三组：破坏细胞壁的离子液体、通过细胞壁渗透和代谢改变发挥毒性的离子液体，以及仅影响细胞代谢的离子液体。
