Corvis Yohann, Korchowiec Beata, Korchowiec Jacek, Badis Mounia, Mironiuk-Puchalska Ewa, Fokt Izabela, Priebe Waldemar, Rogalska Ewa
Groupe d'Etude des Vecteurs Supramoléculaires du Médicament, Faculté des Sciences, BP 239, UMR 7565 CNRS/Nancy Université, 54506 Vandoeuvre-lès-Nancy cedex, France.
J Phys Chem B. 2008 Sep 4;112(35):10953-63. doi: 10.1021/jp803072b. Epub 2008 Aug 12.
The two new crown ethers presented in this study were synthesized in order to investigate two important features of ionophores, namely metal cation complexation and interfacial properties, and the way in which they interrelate. The two derivatives were conceived as analogs of membrane phospholipids with respect to their amphiphilicity and geometry. They contain a hydrophilic 1,1'-dioxo-3,3'-dithio-14-crown ether headgroup and bear two myristoyl or stearoyl lateral chains. The length of the myristoyl and stearoyl derivatives in an extended conformation is comparable with the thickness of the individual leaflets of cell membranes. The membrane-related and complexation properties of the two crown ether derivatives were studied in monomolecular films spread on pure water and on aqueous solutions of mono-, di-, and trivalent metal salts. The properties of the monolayers are described quantitatively using thermodynamic models. The compression isotherms of the monolayers formed on different subphases show a clear-cut differentiation of the monovalent and di- or trivalent cations with both ligands. This differentiation was interpreted in terms of conformational changes occurring in the crown ether derivatives upon complexation. Molecular modeling indicates that the mono- and divalent cations are coordinated differently by the ligands, yielding complexes with different conformations. The differences of the conformations of the mono- and di- or trivalent cation complexes may be important from the point of view of the interactions with lipid membranes and the biological activity of these potential ionophores.
本研究中合成的两种新型冠醚旨在研究离子载体的两个重要特性，即金属阳离子络合和界面性质，以及它们之间的相互关系。这两种衍生物在两亲性和几何形状方面被设计为膜磷脂的类似物。它们含有亲水性的1,1'-二氧代-3,3'-二硫代-14-冠醚头基，并带有两条肉豆蔻酰基或硬脂酰基侧链。肉豆蔻酰基和硬脂酰基衍生物在伸展构象下的长度与细胞膜单个小叶的厚度相当。在铺展在纯水以及单价、二价和三价金属盐水溶液上的单分子膜中研究了这两种冠醚衍生物的膜相关性质和络合性质。使用热力学模型对单分子层的性质进行了定量描述。在不同亚相上形成的单分子层的压缩等温线显示，两种配体对单价和二价或三价阳离子有明显的区分。这种区分是根据络合时冠醚衍生物中发生的构象变化来解释的。分子建模表明，单价和二价阳离子与配体的配位方式不同，产生具有不同构象的络合物。从与脂质膜的相互作用以及这些潜在离子载体的生物活性的角度来看，单价和二价或三价阳离子络合物构象的差异可能很重要。
