Effect of Phenoxy Acids and Their Derivatives on the Ionic Permeability of Bilayer Lipid Membranes

It has been found that the herbicide 2,4-D has the ability to increase the rate of transport of positive ions of several kinds and inhibit the transport of negatively charged tetraphenylborate ions in lipid bilayer membranes. Only the neutral molecules of 2,4-D are transport active. The ionized 2,4-D molecules do not modify the transport of ions, and do not by themselves permeate through lipid membranes. The results suggest that the enhancement of transport of positively charged ions is dominated by the increase of the ion translocation rate constant. It has been shown that membrane transport of negatively charged tetraphenylborate ions is suppressed by 2,4-D. The effect is dominated by the suppression of translocation of these ions across membrane interior, rather than by the decrease of their adsorption at the membrane surface. It has been shown that the enhancement of nonactin-mediated transport of potassium ions by 2,4-D can be accounted for by a simple carrier model. From the changes of kinetic parameters of nonactin-K+ transport, membrane conductance due to positively charged tetraphenylarsonium ions and also from the changes of membrane conductance and relaxation time constant due to transport of negatively charged tetraphenylborate ions, the changes of the electric potential of the membrane interior have been estimated. The potential of the membrane interior becomes more negative in the presence of 2,4-D and its change is proportional to the aqueous concentration of 2,4-D. The effect of 2,4-D on ion transport was explained by the hypothesis that a layer of 2,4-D molecules is absorbed within the membrane/water interfacial region, and that the 2,4-D molecules are oriented in such a way that their dipole moment is directed toward the aqueous medium. The results suggest that this layer is located in the hydrocarbon side of the interface. The hypothesis has been confirmed by the measurements of changes of electric potential difference across air/water and air/lipid monolayer/water interfaces. It has been found that the electric potential of the nonpolar side of the interface decreases in the presence of neutral molecules of 2,4-D, which is in agreement with the conclusions drawn from the results of membrane experiments. The effect of the other auxin-type phenoxy herbicides, 2,4,5-T and 2,4-DB on lipid bilayer membranes has been found to be similar to that of 2,4-D. In contrast, the phenoxy acid 2,4,6-T, has very little or no herbicidal activity, and at the same time has small effect on ion transport in membranes. Biologically active 2,4-D derivatives, amino acid conjugates of 2,4-D (isoleucine, leucine and valine conjugates) have been found to be also transport active in a manner similar to 2,4-D. Similar conclusions have been drawn from experiments with natural auxin indole acetic acid. The results obtained in this work suggest the existence of correlation between the biological activity of herbicides acting as plant growth regulators and their ability to enhance transport of positively charged ions across lipid membranes. This work provides insight into the physical origin of such activity