Yang S, Bumgarner J G, Kruk L F, Khaledi M G
North Carolina State University, Department of Chemistry, Raleigh 27695-8204, USA.
J Chromatogr A. 1996 Jan 19;721(2):323-35. doi: 10.1016/0021-9673(95)00773-3.
Applications of micellar electrokinetic chromatography (MEKC) in quantitative structure-activity relationships (QSAR) were studied. First, quantitative structure-retention relationships (QSRR), which describe the correlation between logarithm of capacity factor (log k') in MEKC and logarithm of distribution coefficient between 1-octanol and water (log P(ow)), were investigated for 60 aromatic compounds and 9 corticosteroids using three different anionic surfactants [e.g., sodium dodecyl sulfate (SDS), sodium cholate (SC), and lithium perfluorooctane sulfonate (LiPFOS)], one cationic surfactant (C14TAB), and mixed anionic micellar systems. Linear solvation energy relationships (LSER) and solvatochromic parameters were used to shed light on the different log k' vs. log P(ow) relationships of the various surfactants. It was concluded that hydrogen bonding interactions have a great influence on retention behavior in MEKC and its relationships with hydrophobicity. Interestingly, bile salt surfactants (e.g., SC) and mixed bile salt micellar systems provide better correlations for log k' vs. log P(ow) than SDS and/or SDS with buffer additives (e.g., beta-cyclodextrin, urea, and acetonitrile). Using SC micelles, only one line was adequate to describe the relationship between retention in MEKC and hydrophobicity for a group of 60 aromatic compounds. The existence of higher correlation for the SC system was attributed to a similar hydrogen bonding pattern between SC micelles and 1-octanol. In the SDS system, however, three lines were recognized for the congeneric subgroups of compounds. This is due to the hydrogen bond door (HBD) characteristic of SDS micelles that selectively differentiate between the solutes with different hydrogen bond acceptor (HBA) strength, thus demonstrating that retention is not solely based on hydrophobicity. A similar result was observed for a C14TAB-MEKC system, however, the HBA characteristic of C14TAB selectively differentiates between the solutes with different HBD strength. In addition, quantitative retention-activity relationships in MEKC were also investigated for 9 corticosteroids. Two types of biological activities [small intestinal absorption in the rat (log A/NA) and protein binding to human serum albumin (log B/F) were examined in this work. High correlations were observed between bioactivity and log k' in MEKC using bile salt surfactants and mixed bile salt systems.
研究了胶束电动色谱（MEKC）在定量构效关系（QSAR）中的应用。首先，使用三种不同的阴离子表面活性剂[如十二烷基硫酸钠（SDS）、胆酸钠（SC）和全氟辛烷磺酸锂（LiPFOS）]、一种阳离子表面活性剂（C14TAB）以及混合阴离子胶束体系，对60种芳香族化合物和9种皮质类固醇进行了定量结构保留关系（QSRR）研究，QSRR描述了MEKC中容量因子的对数（log k'）与1-辛醇和水之间分配系数的对数（log P(ow)）之间的相关性。使用线性溶剂化能关系（LSER）和溶剂化显色参数来阐明各种表面活性剂不同的log k'与log P(ow)关系。得出结论，氢键相互作用对MEKC中的保留行为及其与疏水性的关系有很大影响。有趣的是，胆盐表面活性剂（如SC）和混合胆盐胶束体系比SDS和/或添加缓冲剂（如β-环糊精、尿素和乙腈）的SDS能提供更好的log k'与log P(ow)相关性。使用SC胶束时，只需一条线就能描述一组60种芳香族化合物在MEKC中的保留与疏水性之间的关系。SC体系存在更高相关性的原因是SC胶束与1-辛醇之间存在相似氢键模式。然而，在SDS体系中，化合物的同系物亚组被识别出三条线。这是由于SDS胶束的氢键供体（HBD）特性能够选择性地区分具有不同氢键受体（HBA）强度的溶质，从而表明保留不仅仅基于疏水性。在C14TAB-MEKC体系中也观察到了类似结果，然而，C14TAB的HBA特性能够选择性地区分具有不同HBD强度的溶质。此外，还对9种皮质类固醇进行了MEKC中的定量保留活性关系研究。在这项工作中考察了两种类型的生物活性[大鼠小肠吸收（log A/NA）和与人血清白蛋白的蛋白结合（log B/F）]。使用胆盐表面活性剂和混合胆盐体系时，在MEKC中观察到生物活性与log k'之间有高度相关性。
