Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany; Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Science, King's College London, London, UK.
Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Colloids Surf B Biointerfaces. 2018 Sep 1;169:298-304. doi: 10.1016/j.colsurfb.2018.05.031. Epub 2018 May 17.
Investigating lipid ion pair formation is important for understanding the mechanisms of lipid-mediated drug resistance in bacteria. In this study we have used the charged amphiphiles dipalmitoylphosphatidylglycerol (DPPG) and dihexadecyldimethylammonium bromide (DHDAB), as a model to evaluate the formation of ion pairs by a combined Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis. FTIR was employed to study the environment of the DPPC headgroup phosphate and lipid/surfactant alkane chains, in vesicles formed by the two amphiphiles mixed in various molar ratios. An increase of the absorbance ratio of 1221-1201 cm in the asymmetric phosphate stretching mode was found to follow a sigmoidal relationship with the proportion of DHDAB, increasing to a plateau above a DPPG/DHDAB 1:1 molar ratio of, providing evidence that the PG headgroup phosphate is involved in ion pairing. A consistent red shift was measured for the position of the symmetric CH stretch band for the lipid/surfactant 1:1 molar ratio mixture, which is indicative of an increased ordering of the hydrophobic chains. The DSC experiments yielded information about the thermotropic and the mixing behaviour of the lipid/surfactant systems. DPPG and DHDAB seem to form an ion pair with cluster compound characteristics at the equimolar ratio. Most interestingly, the DPPG/DHDAB 2:1 molar ratio mixture is characterized by strong intermolecular interactions, which result in a pronounced stabilization of the gel phase, possibly through the formation of a closely-associated ion triplet configuration in which the charges are delocalised across the headgroups.
研究脂质离子对的形成对于理解细菌中脂质介导的药物耐药机制非常重要。在这项研究中，我们使用带电两亲物二棕榈酰磷脂酰甘油（DPPG）和二十六烷基二甲基溴化铵（DHDAB）作为模型，通过傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）分析评估离子对的形成。FTIR 用于研究 DPPC 头部磷酸盐和脂质/表面活性剂烷烃链在两种两亲物以各种摩尔比混合形成的囊泡中的环境。发现不对称磷酸盐伸缩模式的 1221-1201 cm 处的吸收比与 DHDAB 的比例呈 S 形关系增加，在 DPPG/DHDAB 摩尔比为 1:1 以上达到平台，这表明 PG 头部磷酸盐参与了离子对的形成。对于脂质/表面活性剂 1:1 摩尔比混合物的对称 CH 伸缩带的位置测量到一致的红移，这表明疏水性链的有序性增加。DSC 实验提供了有关脂质/表面活性剂系统热特性和混合行为的信息。DPPG 和 DHDAB 在等摩尔比下似乎形成具有簇状化合物特征的离子对。最有趣的是，DPPG/DHDAB 2:1 摩尔比混合物的特点是具有强烈的分子间相互作用，这导致凝胶相明显稳定，可能是通过形成紧密相关的离子三重态结构，其中电荷在头部基团之间离域。
