Design, synthesis, and study of a synthetic barrel-stave supramolecule with p-octiphenyl "staves," beta-sheet "hoops," and hydrophobic exterior as well as internal carboxylate clusters are reported. Ion transport experiments indicate the formation of transmembrane pores at 5 < pH < 7 with nanomolar activity. Blockage of dye efflux from spherical bilayers by external Mg(OAc)(2) and internal 8-aminonaphthalene-1,3,6-trisulfonate is suggestive for weakly cooperative (n = 1.16) formation of aspartate-Mg(2+)-8-aminonaphthalene-1,3,6-trisulfonate complexes within the barrel-stave supramolecule (K(D) = 2.9 mM). Corroborative evidence from structural studies by circular dichroism spectroscopy is provided and discussed with emphasis of the importance of internal charge repulsion for pore formation and future applications toward binding and catalysis within supramolecular synthetic pores.