Engineering of Supramolecular Non-Gated and Gated Channels for Transmembrane Transport of Cation-Anion and Proton

Abstract

The cell membrane protects organelles and prevents unwanted ions and large polar molecules from entering. It maintains essential functions like regulating cell volume, osmotic pressure, pH, and cell signaling. Transmembrane proteins facilitate the transport of various substances to meet cell needs. Scientists have shifted focus from simple ion channels to developing small molecule-based cation or anion channels. However, synthetic cation-anion symporter channels are less explored due to the challenge of selectively transporting both ions. Thus, creating a synthetic channel with dual ion selectivity remains difficult. Therefore, we aimed to develop new artificialsystems that can transport both cations and anions through the selectivity filter of the ion channel. In Chapter 2, we designed a series of bis((R)-(−) mandelic acid)-linked 3,5 diaminobenzoic acid-based self-assembled barrel-rosette ion channel, which selectively transports K+ and ClO4− ions across the lipid bilayer membrane via symport mechanism. Subsequently in Chapter 3, to improve the ion selectivity towards physiologically relevant cations and anions, we introduced heteroditopic [2]catenanes-based molecular machines that can reorient the structure for ion binding and showed the highest transport selectivity towards Na+ and Cl− ions. The heteroditopic [2]catenane was found to be an efficient transport system over its macrocyclic analogues. Detailed studies revealed that [2]catenane systems follow the channel mode of ion transport across the lipid bilayer membrane. To get control over the ion transport process in Chapter 4, we further introduced an inaugural example of a ligand-gated meta dipropynylbenzene-based trimeric barrel-rosette ion channel for selective K+–Cl− cotransport. Sequential addition of CuCl2 and K2EDTA OFF-ON the transport activity of the channel, validating its ligand-based response towards ion transport process. Additionally, proton transport is crucial for the production of proton-exchange membranes used in fuel cells and for facilitating proton-coupled electron transfer reactions, such as oxygen reduction. Specific to proton transport, despite the availability of some selective proton carriers (e.g., fatty acids, FCCP, 2,4-dinitrophenol, niclosamide, etc.), artificial proton channels with high selectivity remain largely unexplored. Here Chapter 5, we developed a pioneering example of a meta-dipropynylbenzene-based dimeric barrel-rosette ion channel for the efficient transport of protons by rejecting the salts and water in accordance with the Grotthuss mechanism. Interestingly, this synthetic mimic showed higher proton transport efficiency than natural and synthetic analogues of proton transporter gramicidin and FCCP. Moreover, the sequential addition of CuCl2 and K2EDTA showed reversible OFF-ON the proton transport activity of the channel by disassembling and reassembling the water wire in the cavity of the dimeric rosette, validating its ligand-based response towards the proton transport process. In summary, different supramolecular architectures were used to generate synthetic non-gated and gated transmembrane ion channels for transmembrane transport of cation-anion and proton.