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Abstract

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.

Synthetic multifunctional pores: deletion and inversion of anion/cation selectivity using pM and pH

“…3- 7 The formation of multifunctional pores has been demonstrated in spherical bilayer membranes, i.e., EYPC SUVs or LUVs, for both cases. For instance, α-helix recognition by cationic supramolecule 1 in polarized vesicles confirmed the existence of multifunctional pores with internal RH dyads.…”

“…4,5, 7 Ion channel characterization of barrels 1 and 2 in a planar bilayer has not been reported so far.…”

Controlling supramolecular polymerization through multicomponent self‐assembly

“…Due to the spacial proximity and electrostatic repulsion of the multiply charged bases or acids in these synthetic pores, the intrinsic pK a of the base/acid is shifted, an observation which the authors described using the intermediate internal charge repulsion (ICR) model. 312,313 Lack of ICR was suggested to account for "implosion," low ICR for contraction, high ICR for expansion, and excess ICR for "explosion" of the b-barrels pores. Contributions of the surrounding bilayer also had to be taken into account: the external membrane pressure (EMP) model was suggested to protect the overcharged barrels from exploding and to promote the implosion of undercharged barrels, 312,313 an effect that has important consequences for the catalytic activity of the synthetic pores.…”

“…85,[308][309][310][311] A similar effect has been reported by Matile and coworkers in the b-sheet directed self-assembly of poctiphenyl b-barrel pores embedded in lipid bilayers. 312 Weakening of the basic character of protonated lysine and histidine side chains (apparent pK a of 7 and 4.5, respectively), as well as a weakening of the acidic character of aspartic acid side chains (apparent pK a of 6) was observed. Due to the spacial proximity and electrostatic repulsion of the multiply charged bases or acids in these synthetic pores, the intrinsic pK a of the base/acid is shifted, an observation which the authors described using the intermediate internal charge repulsion (ICR) model.…”

Rigid-Rod β-Barrel Ion Channels with Internal “Cascade Blue” Cofactors − Catalysis of Amide, Carbonate, and Ester Hydrolysis

“…( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002) for example, linear concentration dependence of transport [17] and milieu-independent esterase activity [4] Ϫ support an identical suprastructure for β-barrel 1 in water and in bilayer membranes. Intermediate internal charge repulsion (ICR) at 4 Ͻ pH Ͻ 6 is required to stabilize the aqueous space within p-octiphenyl β-barrels.…”