Blood-brain barrier permeation : molecular parameters governing passive diffusion

Fischer, H. and Gottschlich, R. and Seelig, A.. (1998) Blood-brain barrier permeation : molecular parameters governing passive diffusion. The Journal of Membrane Biology, 165 (3). pp. 201-211.

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Official URL: http://edoc.unibas.ch/dok/A5258479

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53 compounds with clinically established ability to cross or not to cross the blood-brain barrier by passive diffusion were characterized by means of surface activity measurements in terms of three parameters, i.e., the air-water partition coefficient, Kaw, the critical micelle concentration, CMCD, and the cross-sectional area, AD. A three-dimensional plot in which the surface area, AD, is plotted as a function of K-1aw and CMCD shows essentially three groups of compounds: (i) very hydrophobic compounds with large air-water partition coefficients and large cross-sectional areas, AD < 80 A2 which do not cross the blood-brain barrier, (ii) compounds with lower air-water partition coefficients and an average cross-sectional area, AD congruent with 50 A2 which easily cross the blood-brain barrier, and (iii) hydrophilic compounds with low air-water partition coefficients (AD > 50 A2) which cross the blood-brain barrier only if applied at high concentrations. It was shown that the lipid membrane-water partition coefficient, Klw, measured previously, can be correlated with the air-water partition coefficient if the additional work against the internal lateral bilayer pressure, pibi = 34 +/- 4 mN/m is taken into account. The partitioning into anisotropic lipid membranes decreases exponentially with increasing cross-sectional areas, AD, according to Klw = const. Kaw exp(-ADpibi/kT) where kT is the thermal energy. The cross-sectional area of the molecule oriented at a hydrophilic-hydrophobic interface is thus the main determinant for membrane permeation provided the molecule is surface active and has a pKa < 4 for acids and a pKa > 10 for bases.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig A)
UniBasel Contributors:Seelig-Löffler, Anna
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Nov 2017 12:45
Deposited On:22 Mar 2012 13:20

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