The lessons learned from p-octiphenyl beta-barrel pores are applied to the rational design of synthetic multifunctional pore 1 that is unstable but inert, two characteristics proposed to be ideal for practical applications. Nonlinear dependence on monomer concentration provided direct evidence that pore 1 is tetrameric (n = 4.0), unstable, and "invisible," i.e., incompatible with structural studies by conventional methods. The long lifetime of high-conductance single pores in planar bilayers demonstrated that rigid-rod beta-barrel 1 is inert and large (d approximately 12 A). Multifunctionality of rigid-rod beta-barrel 1 was confirmed by adaptable blockage of pore host 1 with representative guests in planar (8-hydroxy-1,3,6-pyrenetrisulfonate, KD = 190 microM, n = 4.9) and spherical bilayers (poly-L-glutamate, KD < or = 105 nM, n = 1.0; adenosine triphosphate, KD = 240 microM, n = 2.0) and saturation kinetics for the esterolysis of a representative substrate (8-acetoxy-1,3,6-pyrenetrisulfonate, KM = 0.6 microM). The thermodynamic instability of rigid-rod beta-barrel 1 provided unprecedented access to experimental evidence for supramolecular catalysis (n = 3.7). Comparison of the obtained kcat = 0.03 min(-1) with the kcat approximately 0.18 min(-1) for stable analogues gave a global KD approximately 39 microM3 for supramolecular catalyst 1 with a monomer/barrel ratio approximately 20 under experimental conditions. The demonstrated "invisibility" of supramolecular multifunctionality identified molecular modeling as an attractive method to secure otherwise elusive insights into structure. The first molecular mechanics modeling (MacroModel, MMFF94) of multifunctional rigid-rod beta-barrel pore hosts 1 with internal 1,3,6-pyrenetrisulfonate guests is reported.