Properties and Permeability of Hypericin and Brominated Hypericin in Lipid Membranes
Properties and Permeability of Hypericin and Brominated Hypericin in Lipid Membranes
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DOI：
10.1021/ct9002702
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发表时间：
2009-12-01
影响因子：
5.5
通讯作者：
Eriksson, Leif A.
中科院分区：
文献类型：
--
作者：
Eriksson, Emma S. E.;dos Santos, Daniel J. V. A.;Eriksson, Leif A.
金丝桃素是一种天然存在于圣约翰草中的取代苯并二烯醌，其光敏性很有前途，因此有人建议将其用于光动力治疗。目前正在研究其结构修饰衍生物，以产生更有效的金丝桃素光敏剂。由于光激发而产生的金丝桃素的强大作用背后的详细机制，以及细胞内的定位和运输都还没有完全了解。本文通过分子动力学模拟研究了金丝桃素在双棕榈酰磷脂酰胆碱脂质膜中的性质和渗透性，以及用一个或四个溴原子取代金丝桃素的修饰。由于与疏水脂质内部和极性水环境的竞争相互作用，这些分子被发现在脂质最密集的区域积聚。通过分析径向分布函数和系统部件的密度分布，证实了这一点。计算出的自由能谱显示，在分子进入脂质的运输过程中，自由能发生了很大的负变化，这也支持了这一发现。渗透系数表明，含一溴的金丝桃素在膜系统中的扩散速度最快。
The promising photosensitizing properties of hypericin, a substituted phenanthroperylene quinone naturally found in Saint John's wort, has led to the proposal that it can be utilized in photodynamic therapy, Structurally modified derivatives are at the present time being investigated to generate a more effective hypericin photosensitizer. Neither the detailed mechanism behind the powerful action of hypericin, arising as a result of light excitation, nor the intracellular localization and transportation is still fully understood. In the present work, molecular dynamics simulations have been performed to study the properties and the permeability of hypericin and modifications thereof, substituted with one or four bromine atoms, in a dipalmitoylphosphatidylcholine lipid membrane. The molecules were found to accumulate in the most dense region of the lipids due to competing interactions with the hydrophobic lipid interior and the polar aqueous environment. This was confirmed by analyzing the radial distribution functions and by the density profiles of the system components. Calculated free energy profiles display large negative changes in free energy for the transport process of the molecules into the lipids, which also support this finding. Permeability coefficients show overall fastest diffusion in the membrane system for hypericin containing one bromine.