Univ., Diss.--Regensburg, 2002.

The compound 3-phenylindole (3PI) is a particularly active antimicrobial which interacts with phospholipids in fungal mycelia membranes, and which strongly inhibits the uptake of phosphate into fungal mycelia. The physical effects of 3PI on ion transport across bilayer lipid membranes composed of phosphatidylcholine/cholesterol have been investigated using three lipophilic ions and one ion/carrier complex. It was found that 3PI increased the electrical conductivity induced by the lipophilic cation (tetraphenylarsonium) and by the positively charged complex (nonactin-K('+)) by several orders of magnitude whereas 3PI decreased the conductivity induced by the two lipophilic anions (tetraphenylborate, dipicrylamine) by a factor of less than ten. These conductivity changes are explained as a combination of changes in the electrostatic and in the non-electrostatic properties of the bilayer. The electrostatic potential of the bilayer interior was shown to decrease in the presence of 3PI, a phenomenon which was also confirmed by measurements of the surface potential of phosphatidylcholine/cholesterol monolayers. The changes in non-electrostatic properties of the bilayer are qualitatively discussed in terms of increased bilayer fluidity or decreased bilayer thickness brought about by the presence of 3PI. The partition coefficient of the lipophilic anions, as determined by the voltage-step transient current technique, decreased slightly when 3PI was present in the aqueous phase. From the voltage dependence of the normalized steady state conductivity it was shown that 3PI did not kinetically limit tetraphenylarsonium transport but that it did kinetically limit nonactin-K('+) transport at concentrations greater than 25 (mu)M 3PI. The theory of carrier-mediated transport predicts the occurrence of transient currents in the kinetically limited regime but no transients were detected for nonactin-K('+) in the presence of 80 (mu)M 3PI. A method for analyzing the adsorption of neutral lipophilic molecules onto lipid monolayers has been presented, and by this method it was found that the partition coefficient of 3PI onto phosphatidylcholine/cholesterol monolayers was 1.3 x 10('-4) m and that the maximum adsorbed surface number density of 3PI was 1.1 x 10('-6) moles/m('2). From the experimental changes in monolayer surface potential as a function of adsorbed surface number density, a value for the normal component of the dipole moment of 3PI was obtained.