Design, synthesis, and activity of membrane-disrupting bolaphiles

Article abstract of DOI:10.1021/ja00171a026

Four new classes of bolaphiles ("double-headed" single-chain surfactants) have been prepared, via condensation of an homologous series of linear saturated, olefinic, and acetylenic α,ω-dicarboxylic acids with hexaethylene glycol, and evaluated for their ability to induce the release of 5(6)-carboxyfluorescein (CF) entrapped within large unilamellar vesicles derived from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Operationally, the membrane-disrupting activity of the bolaphiles has been found to vary by a factor of ca. 100, when the total number of carbon atoms which separate the carboxylate moieties range from 12 to 24; the most active bolaphile is approximately three times more active than Triton X-100. When the affinity of the bolaphiles toward POPC membranes is considered, the intrinsic membrane-disrupting activity varies by a factor of ca. 230. A "loop" model is proposed to account for the general trends in bolaphile activity that are observed, where the depth of loop penetration and loop width are presumed to be the key factors involved in determining membrane-disrupting activity. The potential utility of these surfactants as antimicrobial agents, and as anti-HIV agents in particular, is briefly discussed.