Polymerized forms of saturated, olefinic, and acetylenic bolaphiles (double-headed surfactants) have been prepared by condensation of a series of α,ω-dicarboxylic acids with tridecaethylene 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-snglycero-3-phosphocholine (POPC). Each amphiphilic polymer was found to have substantially greater membrane-disrupting activity than that found for Triton X-100; operationally, one was more than 300 times greater in activity. Comparison of each supramolecular surfactant with its corresponding bolaphile demonstrates, in nearly all cases, that a significant enhancement in membrane-disrupting activity is provided through polymerization, and that the magnitude of this amplification decreases, exponentially, as the length of the hydrophobic segment increases. In the most striking case, the disruptive power of the supramolecular surfactant was at least 3 orders of magnitude greater than its monomeric counterpart. As one goes from saturated to olefinic to acetylenic polyesters, longer hydrophobic segments are required in order to reach a maximum in activity. From a practical standpoint, supramolecular surfactants extend nonionic detergents into a new and uncharted domain in membrane-disrupting activity. © 1990, American Chemical Society. All rights reserved.
