Permeation of permanently positive charged molecules through artificial membranes--influence of physico-chemical properties

Eur J Pharm Sci. 2007 May;31(1):32-42. doi: 10.1016/j.ejps.2007.02.001. Epub 2007 Feb 11.


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 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)<0.1x10(-6)cm/s), four medium permeabilities (0.1x10(-6)< or =P(e)<1x10(-6)cm/s) and six were highly permeable (P(e)> or =1x10(-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.

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Heterocyclic Compounds, 3-Ring / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Isoquinolines / chemistry
  • Membranes, Artificial*
  • Models, Statistical
  • Molecular Conformation
  • Molecular Structure
  • Permeability
  • Quaternary Ammonium Compounds / chemistry*
  • Rhodamines / chemistry
  • Static Electricity


  • Heterocyclic Compounds, 3-Ring
  • Heterocyclic Compounds, 4 or More Rings
  • Isoquinolines
  • Membranes, Artificial
  • Quaternary Ammonium Compounds
  • Rhodamines
  • rhodamine 110