Intermediate internal charge repulsion (ICR) is required to create synthetic pores with large, stable, transmembrane, and variably functionalized space. This conclusion is drawn from maximal transport and, in one case, catalytic activity of p-octiphenyl ß-barrel pores with internal lysine, aspartate, and histidine residues around pH 7, 6, and 4.5, respectively. pKa Simulations corroborate the experimental correlation of intermediate ICR with activity and suggest that insufficient ICR causes pore implosion' and excess ICR pore explosion'. Esterolysis experiments support the view that the formation of stable space within multifunctional p-octiphenyl ß-barrels requires more ICR in bilayer membranes than in H2O. Multivalency effects are thought to account for p-octiphenyl ß-barrel expansion with increasing number of ß-sheets, and proximity effects for unchanged pH profiles with increasing ß-sheet length. Q-TOF-nano-ESI-MS barrel-denaturation experiments indicate that contributions from internal counterion effects are not negligible. The overall characteristics of p-octiphenyl ß-barrel pores with internal lysine, aspartate, and histidine residues, unlike de novo a-barrels' and similarly to certain biological channels, underscore the usefulness of rigid-rod molecules to preorganize complex multifunctional supramolecular architecture.