Ligand‐Gated Synthetic Ion Channels

Abstract

Supramolecular pi-stack architecture is fundamental in DNA chemistry but absent in biological and synthetic ion channels and pores. Here, a novel rigid-rod pi-stack architecture is introduced to create synthetic ion channels with characteristics that are at the forefront of rational design, that is, ligand gating by a conformational change of the functional supramolecule. Namely, the intercalation of electron-rich aromatics is designed to untwist inactive electron-poor helical pi-stacks without internal space into open barrel-stave ion channels. Conductance experiments in planar lipid bilayers corroborate results from spherical bilayers and molecular modeling: Highly cooperative and highly selective ligand gating produces small, long-lived, weakly anion selective, ohmic ion channels. Structural studies conducted under conditions relevant for function provide experimental support for helix-barrel transition as origin of ligand gating. Control experiments demonstrate that minor structural changes leading to internal decrowding suffice to cleanly annihilate chiral self-organization and function.

The determination of the ion selectivity of synthetic ion channels and pores in vesicles

“…To summarize, the anion/cation selectivity of ion channels 3 and 4 obtained from the HPTS assay was identical with that obtained in BLMs. [7][8][9][10] The selectivity sequence of anion channel 4 obtained from the HPTS assay was partially identical with that obtained in The anion/cation selectivity of pore 6 obtained by comparison of CF and ANTS/DPX assay was identical with that obtained in BLMs. 13,15 The same was true for the deletion of the cation selectivity of pore 6 with Mg 2þ .…”

“…8 The cationic interior of ion channel 4 was as well reflected in P Cl À =P K þ ¼ 3:0 as the anionic interior of pore…”

“…The electron-deficient rigid-rod p-stack architecture of ion channel 3 was designed to open in response to chargetransfer complex formation with intercalating pdonors. 7,8 In this case, experimental evidence for ligand gating was of highest importance to verify the functional innovation of interest. The determination of the ion selectivity was nothing more (and nothing less) than part of a clean characterization of the obtained ligand-gated ion channel.…”

Artificial tongues and leaves

“…Amides were added at both sides of the NDI to orient the π-stacks with H-bonded chains [45,46]. Denaturation-corrected Hill analysis demonstrated self-assembly into tetrameric architecture as expected for π-helix 12 [42].…”

“…Functional and structural studies revealed that the helix-barrel transition from photosystem 12B to ion channel 19 is highly cooperative, sensitive, and selective with regard to ligand and channel structure. Ion channels 19 are small, anion-selective, ohmic, and remarkably homogenous considering the complexity of the architecture [46]. In summary, it is possible to synthesize supramolecular architectures that can function as ion channels, pores, or photosystems.…”