QSAR analysis of substituent effects on tambjamine anion transporters† ‡ †Electronic supplementary information (ESI) available: Synthesis of new compounds, anion transport studies and details of the QSAR analysis. See DOI: 10.1039/c5sc03932k ‡The underlying research data for this paper are available in accordance with EPSRC open data policy from http://dx.doi.org/10.5258/SOTON/384138

A QSAR analysis of the transmembrane anion transport activity of 43 synthetic tambjamine analogs allowed rationalization of this activity according to their lipophilicity and structural parameters. 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.