Permeability of psoralen derivatives in lipid membranes

被引:27
作者
dos Santos, Daniel J. V. A.
Eriksson, Leif A. [1 ]
机构
[1] Univ Orebro, Orebro Life Sci Ctr, S-70182 Orebro, Sweden
[2] Univ Orebro, Dept Nat Sci, S-70182 Orebro, Sweden
[3] Tech Univ Darmstadt, Eduard Zintl Inst Inorgan & Phys Chem, D-64287 Darmstadt, Germany
关键词
D O I
10.1529/biophysj.105.077156
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Molecular dynamics simulations have been performed to explore the distribution and translocation of a set of furocoumarins (psoralen derivatives) inside saturated and partially unsaturated lipid membranes. Within the simulations, strong accumulation of the photodynamic drugs is observed near the polar headgroup region, although the populations also extend out into the membrane/water interface as well as to the membrane center. The computed transverse (D-z) diffusion coefficients are in the range 0.01-0.03 x 10(-5) cm(2) s(-1)-significantly slower than those reported for small molecules like water, ethane, and ammonia-and are related to the low mobility inside the polar headgroup region. Trimethylpsoralen (TMP) has a very low free energy barrier to transversion, only similar to 10 kJ/mol, whereas 5-and 8-methoxy psoralens (5-MOP, 8-MOP) have the largest barriers of the compounds studied-between 25 and 40 kJ/mol. Upper bounds to the permeation coefficients, obtained by integrating the resistance profiles across the bilayers, range from 5.2 x 10(-8) cm s(-1) for TMP to 4.1 x 10(-12) cm s(-1) for 5-MOP. The current simulations explain the high level of furocoumarin-lipid membrane complexes found in experimental studies of albino Wistar rats exposed to topical application of 8-MOP, and points to the possibility of membrane photodamage as a viable mechanism in psoralen ultraviolet-A treatment.
引用
收藏
页码:2464 / 2474
页数:11
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