Design, synthesis, and esterase and ion channel activity of a novel barrel-stave supramolecule with hydrophobic exterior and histidine-rich interior are reported. Voltage-dependent binding of pyrenyl-8-oxy-1,3,6-trisulfonates by histidines within p-octiphenyl beta-barrels (and not monomers) via ionic (and not hydrophobic) interactions (K(D), K(I), K(M) < 1 microM) is the basis for superb esterolytic proficiency up to (k(cat)/K(M))/k(uncat) = 9.6 x 10(5) in water and bilayer membranes. The conductance of labile ion channels formed in planar bilayer membranes is shown to be reduced by 8-hydroxypyrene-1,3,6-trisulfonate on the single- and multichannel level. [reaction: see text]

Future stochastic biomimetic chemistry within toroidal supramolecules will depend on the availability of large, transmembrane, and functionalized internal space of high stability, four properties that characterize the nanopore formed by the hexameric, cationic rigid‐rod β‐barrel (see schematic representation).

Herein, we describe the design, synthesis, structure, and function of synthetic, supramolecular b-barrel models. Assembly of octi(p-phenylene)s with complementary -Lys-Leu-Lys-NH 2 andGlu-Leu-Glu-NH 2 side chains yielded water-soluble rigid-rod b-barrels of precise length and with flexible diameter. A hydrophobic interior was evidenced by guest encapsulation. Host ± guest complexes with planarized, monomeric bcarotene within tetrameric rigid-rod bbarrels, and disc micellar astaxanthin J-aggregates surrounded by about dodecameric rigid-rod ªbicycle tiresº were prepared from mixed micelles by dialytic detergent removal. The significance of these findings for future bioorganic chemistry in confined, intratoroidal space is discussed in comparison with pertinent biological examples.

Dedicated to Prof. Wolf-Dietrich Woggon on the occasion of his 60th birthday 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 b-barrel pores with internal lysine, aspartate, and histidine residues around pH 7, 6, and 4.5, respectively. pK a 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 b-barrels requires more ICR in bilayer membranes than in H 2 O. Multivalency effects are thought to account for p-octiphenyl b-barrel expansion with increasing number of b-sheets, and proximity effects for unchanged pH profiles with increasing b-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 bbarrel 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. Fig. 2. Axial view and peptide sequences of the p-octiphenyl b-barrels 1 ± 6 from Fig. 1 (8-stranded) and Fig. 3 (6stranded). One-letter abbreviations are used for amino acids (L Leu, K Lys, H His, D Asp; G ÀOCH 2 COÀ ). n number of acid/bases per supramolecule. In molecular models [9], internal distances are a % 5 ä, b % 4 ä (1: ca. 12 ä), c % 7 ä (1: ca. 23 ä), c' % 14 ä, and d % 7 ä.