Recognition of Polarized Lipid Bilayers by p-Oligophenyl Ion Channels:  From Push−Pull Rods to Push−Pull Barrels

Design, synthesis, and evaluation of 1⁴-methoxy-8⁴-methylsulfonyl-2²,3³,4²,5³,6²,7³-hexa(Gla-Leu-Lys-Leu-NH₂)-p-octiphenyl (1) and 1⁴,8⁴-bismethoxy-2²,3³,4²,5³,6²,7³-hexa(Gla-Leu-Lys-Leu-NH₂)-p-octiphenyl (2) are described (Gla = −OCH₂CO−). Nanomolar concentrations of push−pull rod 1 are found to suffice to selectively form ion channels in polarized spherical bilayer membranes composed of egg yolk phosphatidylcholine. Exponential dependence of the ion-channel activity on membrane polarization reveals a gating charge of 0.85/channel. Independence of the activity of push−push rod 2 on membrane potential demonstrates that cell membrane recognition originates from the axial dipole in push−pull rod 1. Nonlinear concentration dependence of activity at −180 mV indicates parallel self-assembly of push−pull rod 1 into a tetrameric barrel-stave supramolecule.