Anion transport is an essential cellular function facilitated by membrane-bound ion channels. Diseases in which genetic problems affect the structure of ion channels and hence reduce or stop the flow of anions through the membrane are known as channelopathies and include cystic fibrosis (CF). In CF, reduction in the flow of chloride and bicarbonate through epithelial cell membranes in the lungs limits water osmosis, which leads to the formation of sticky mucus and continual lung infections, reducing the life expectancy of CF patients. It has been proposed that small molecules which can facilitate anion transport through cell membranes, known as a 'channel replacement therapy', may ameliorate the symptoms of CF and other channelopathies by replacing the function of faulty channels. Small molecule anion transporters can dissipate pH gradients across lipid bilayer membranes. The natural product prodigiosin is one such transporter capable of depolarising acidic compartments within cancer cells. Prodigiosin functions as a H + /Cl -cotransporter, protonating, binding chloride and then diffusing across the lipid bilayer. However, other synthetic small molecule transporters can diffuse pH gradients either by functioning as weak acid protonophores or by transporting deprotonated fatty acid carboxylate head groups, which, when reprotonated, can diffuse back across the membrane. Shin and co-workers have shown that transporters that facilitate chloride transport across lipid bilayer membranes can trigger apoptosis in cancer cells, whilst compounds capable of transporting HCl can increase the pH in lysosomes in cells, interfering with autophagy. Consequently, significant efforts have been directed towards developing compounds that transport chloride without dissipating pH gradients, as well as compounds capable of facilitating efficient HCl transport. Fluorination of anionophore scaffolds has been used to adjust their overall anion binding strength and lipophilicity, resulting in more effective transmembrane anion transporters across many classes of compounds, including tripodal and tetrapodal thioureas and o-phenylenediamine-based bis ureas. Macrocycles offer the ability to tune and customise the exterior of the scaffold and, ultimately, the molecular properties of the overall structure without impeding the anion binding ability of the central cavity. Additionally, macrocyclic structures offer greater encapsulation and binding site preorganisation, harbouring a more favourable and size-selective environment for anion binding, which may result in high transport efficiency and anti-Hofmeister selectivity. The potent combination was demonstrated in previously reported Cl -selective fluorinated tetraurea macrocycle, which achieved Cl -binding constants >10 5 M -1 in >50% aqueous mixtures and could perform highly efficient H + /Cl -cotransport. A recent study on a series of fluorinated macrocyclic bambus [6]urils demonstrated very efficient and selective Cl -/HCO3 -antiport across cell membranes. The increase in transport efficiency conveyed through scaffold fluorination also increases transporter lipophilicity. Both lipophilicity and solubility are important aspects of transporter design; anion transporters with an optimal lipophilic balance are capable of efficiently permeating and traversing the lipid bilayer. Very efficient anion transporters like the fluorinated tetraurea macrocycle can be used at significantly lower concentrations, enabling lower amounts of a potentially more insoluble but highly active transporter to be used. Talukdar and co-workers reported on three benzimidazolyl hydrazone H + /Cl -co-transporters and, using a modified HPTS assay, achieved extremely high transport activities at low transporter loading, between 0.00017-0.000022 mol%. In 2019, Smith and co-workers reported the synthesis and anion binding properties of macrocyclic tetralactams, including tetralactam 4a (Figure ), which formed stable complexes with anions like Cl -and F -. However, the anion transport abilities of the tetralactam scaffold was not studied.