The transmembrane anion transport activity of 43 synthetic molecules based on the structure of marine
alkaloid tambjamine were assessed in model phospholipid (POPC) liposomes. The anionophoric activity
of these molecules showed a parabolic dependence with lipophilicity, with an optimum range for
transport efficiency. Using a quantitative structure–transport activity (QSAR) approach it was possible to
rationalize these results and to quantify the contribution of lipophilicity to the transport activity of these
derivatives. While the optimal value of log P and the curvature of the parabolic dependence is a property
of the membrane (and so similar for the different series of substituents) we found that for relatively
simple substituents in certain locations on the tambjamine core, hydrophobic interactions clearly
dominate, but for others, more specific interactions are present that change the position of the
membrane hydrophobicity parabolic envelope.
