MOE Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Department of Chemistry , Tsinghua University , Beijing 100084 , People's Republic of China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering , Southeast University , Nanjing 210096 , People's Republic of China.
J Phys Chem B. 2019 Jul 5;123(26):5474-5482. doi: 10.1021/acs.jpcb.9b03562. Epub 2019 Jun 20.
Among various applications, ionic liquids (ILs) have been used as antimicrobial agents in laboratories, possibly through induction of the leakage of bacteria. A molecular-level understanding of the mechanism that describes how ILs enhance the permeation of membranes is still lacking. In this study, the effects of imidazolium-based ILs with different alky chain lengths on the structure and phase behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), which is a representative bacteria-membrane-rich lipid, have been investigated. By employing differential scanning calorimetry and synchrotron small- and wide-angle X-ray scattering techniques, we found that ILs with longer alkyl chains influenced the phase behavior more effectively, and lower IL concentrations are needed to induce phase separation for both lamellar liquid crystalline phase and nonlamellar inverted hexagonal phase of POPE. Interestingly, the IL with an alkyl chain of 12 carbon atoms ([Cmim]Cl) shows a difference. It exhibits a stronger disturbing effect on the POPE bilayer structure than [Cmim]Cl, indicating that the ability of ILs to influence the membrane structures is dependent not only on the alkyl chain length of ILs, but also on the degree of matching of the alkyl chain lengths of ILs and lipids. The new lamellar and nonlamellar structures induced by ILs both have smaller repeat distances than that of pure POPE, implying thinner membrane structures. Data of the fluorescence-based vesicle dye leakage assay are consistent with these results, particularly the defects caused by IL-induced phase separation can enhance the membrane permeability markedly. The present work may shed light on our understanding of the antimicrobial mechanism of ILs.
在各种应用中，离子液体（ILs）已被用作实验室中的抗菌剂，可能是通过诱导细菌泄漏。然而，对于描述 ILs 如何增强膜渗透的机制，我们仍然缺乏分子水平的理解。在这项研究中，研究了具有不同烷基链长度的咪唑基 ILs 对 1-棕榈酰-2-油酰磷脂酰乙醇胺（POPE）结构和相行为的影响，POPE 是一种代表性的富含细菌膜的脂质。通过差示扫描量热法和同步辐射小角和广角 X 射线散射技术，我们发现，具有较长烷基链的 IL 更有效地影响相行为，并且需要更低的 IL 浓度才能诱导 POPE 的层状液晶相和非层状反相六角相的相分离。有趣的是，具有 12 个碳原子烷基链的 IL([Cmim]Cl) 表现出不同的差异。它对 POPE 双层结构的干扰作用强于 [Cmim]Cl，表明 IL 影响膜结构的能力不仅取决于 IL 的烷基链长度，还取决于 IL 和脂质的烷基链长度的匹配程度。IL 诱导的新层状和非层状结构的重复距离都比纯 POPE 小，这意味着膜结构更薄。基于荧光的囊泡染料泄漏测定法的数据与这些结果一致，特别是由 IL 诱导的相分离引起的缺陷可以显著增强膜通透性。这项工作可能有助于我们理解 ILs 的抗菌机制。
