Synthetic multifunctional pores that open and close in response to chemical stimulation

Self‐Assembled Artificial Transmembrane Ion Channels

“…In this case, p-octiphenylene rods functionalized with naphthalenediimide groups 26 initially assembled into p-helices which act as closed ion channels (Figure 1.9A,B). This type of blockage gating has been demonstrated with a cucurbituril-based channel that is blocked by acetylcholine [34] as well as with a b-barrel pore blocked by polyglutamate [35]. This type of blockage gating has been demonstrated with a cucurbituril-based channel that is blocked by acetylcholine [34] as well as with a b-barrel pore blocked by polyglutamate [35].…”

Molecular Recognition by Synthetic Multifunctional Pores in Practice: Are Structural Studies Really Helpful?

“…Realized examples display inversion of ion selectivity (e.g., anionic pore 2 with internal Mg 2+ becomes anion selective, cationic pore 5 with internal phosphate, cation selective), [12,20] induction of selective transport of guest compounds, [26] and pH insensitivity (pore 7 with external "cushions"). [31] The rich collection of recognized guests includes carbohydrates, inositols, nucleotides, and higher aromatics such as fullerenes, calixarenes, pyrenes, naphthalenes, and p-oligophenylenes; macromolecules such as polypeptides, polysaccharides, oligonucleotides, and polyacetylenes; and supramacromolecules such as B-DNA. In addition, small inorganic ions such as magnesium cations or phosphate anions can be recognized.…”

“…[3,23] 2) The surrounding bilayer is not just a hydrophobic solvent, but a supramolecular host that is part of the suprastructure of the included multifunctional guest. [3,12,30,31] 3) The active synthetic multifunctional pore 2-9 is often formed by a small fraction of the added rod 1. A major fraction remains in an unknown inactive form that is not relevant for function but detected exclusively by conventional methods for structure determination.…”

“…Structural information accessible from functional studies includes ᭹ inner pore diameters from size-exclusion (Figs. 2,5) [31] and single-pore conductance experiments (the latter informing also on the number and kinetic stability of active structures [8][9][10]12,20,21,23,25,31,56,57] ); ᭹ aggregation number and/or pore stability from the dependence of activity on monomer concentration; [23] ᭹ symmetry of self-assembly from voltage dependence; [8,10,20,21,23,57,58] ᭹ internal functional groups from ion selectivities, [20,11,12,23,28,52,] pH profiles, [14,12,25] as well as multifunctionality (Fig. 2).…”

“…6). [31] This template effect from the internal guest on the structure of the surrounding host is accompanied by a template effect from the host on the structure of the guest: Comparison of the energy of complex 13 with random-coil and a-helical blocker 12 suggest that the b-barrel pore will cause a-helix nucleation to maximize the functional group density of the guest within the pore. These template effects are examples of structural insights that are accessible by molecular modeling, but cannot be determined experimentally, at least not without extraordinary efforts.…”