Voltage‐Switchable HCl Transport Enabled by Lipid Headgroup–Transporter Interactions

Abstract

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Prospects and Challenges in Anion Recognition and Transport

“…37 In more recent studies, Gale and co-workers reported unexpected behavior of several high-affinity anion transporters, such as 28. 39,40 They were active in H + /Cl À symport and Cl À /NO 3 À exchange but failed to facilitate the uniport of H + or Cl À ions. This has been attributed to the strong interaction between anion transporters and the phosphate headgroup of lipids, which inhibits the transmembrane diffusion of free transporters suppressing the uniport process but not the exchange process, which does not require free-transporter diffusion.…”

“…This mechanism also leads to interesting voltage-dependent transport properties. 39 Gale and Howe also reported a prototype biomimetic transmembrane pumping system in which externally added fatty acids were used as fuels to generate a pH gradient and pump Cl À ions out of liposomes against their concentration gradient. 41 Matile and co-workers have pioneered the research of using non-covalent interactions other than hydrogen bonds to facilitate transmembrane anion transport.…”

“…Examples include biotin [6]urils decorated with lipophilic side chains (derivatives of 5) as Cl À over HCO 3 À selective transporters, 46 fluorinated bambusurils (derivatives of 4) as selective Cl À /HCO 3 À antiporters that lacked NO 3 À transport activity because ll of NO 3 À binding that was too strong, 47 and a fluorinated tetraurea 10 as a highly active H + /Cl À symporter with selectivity against other common anions. 39 There is more work to do in this area in understanding why some anion transporters are cytotoxic while others are not. This could be due to the degree of anion transport facilitated, whether the transporter is disrupting other chemical or potential gradients in the cell, the particular cell lines studied, the localization of the transporters at the plasma membranes or organelles, or a combination of these and other factors.…”

Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction

“…As such, a proton gradient can be dissipated to pump chloride ions and generate a chloride gradient. The proton gradient generated by the fatty acid pump (Figure 31) was combined with chloride anionophores [91] to pump chloride across a membrane driven by the addition of fatty acids [44b,c] …”

“… Gale's 2019 fatty‐acid‐fuelled anion pump [44b,c] . Chloride anionophores symport chloride and protons across a membrane.…”