Permeation of permanently positive charged molecules through artificial membranes - Influence of physico-chemical properties
Permeation of permanently positive charged molecules through artificial membranes - Influence of physico-chemical properties
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DOI：
10.1016/j.ejps.2007.02.001
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发表时间：
2007-05-01
影响因子：
4.6
通讯作者：
Senner, Frank
中科院分区：
文献类型：
--
作者：
Fischer, Holger;Kansy, Manfred;Senner, Frank
本研究的目的是在平行人工膜透性试验（PAMPA）中研究20种永久带正电分子的透性。其中8种是n -烷基异喹啉盐的衍生物，12种是染料罗丹明110的同系物。罗丹明110系列的12个分子中，有5个分子有一个额外的5个羧基，两个分子有两个羧酸。实验得出的有效渗透率值（P-e）范围为3-4个对数单位。10个化合物具有低渗透率（P-e < 0.1 × 10(-6) cm/s）， 4个化合物具有中渗透率(0.1 × 10（-6) 1 × 10(-6) cm/s）。此外，利用计算出的分子描述符建立了计算模型，并评估了它们预测膜通透性的能力。结果表明，实验P-e值可以用描述分子形状的电子性质和参数来解释。这项工作提供了证据，证明永久带电分子可以具有高的被动膜透性，前提是电荷可以分布在几个芳环系统上。(C) 2007 Elsevier B.V.版权所有
The aim of this study was to investigate the permeation properties of 20 permanently positive charged molecules in the parallel artificial membrane permeability assay (PAMPA). Eight of them were derivatives of the N-alkyl-isoquinolinium salt and 12 were congeners of the dye rhodamine 110. Five out of 12 molecules from the rhodamine 110 series have one additional 5 carboxylic group and two have two carboxylic acids. The experimentally derived effective permeability values (P-e) cover a range of 3-4 log units. Ten compounds showed low permeabilities (P-e < 0.1 x 10(-6) cm/s), four medium permeabilities (0.1 x 10(-6) 1 x 10(-6) cm/s). In addition, computational models were built with a number of calculated molecular descriptors and evaluated for their ability to predict membrane permeability. It turned out that the experimental P-e values can be explained by electronic properties and parameters describing the shape of molecules. This work provides evidence that permanently charged molecules can have high passive membrane permeabilities provided that the charge can be spread over several aromatic ring systems. (C) 2007 Elsevier B.V. All rights reserved.