One effective strategy to achieve chloride selectivity over proton/hydroxide ion transport has been to replace acidic hydrogen bond donors with Lewis acid halogen or chalcogen bonding groups (Figure , top). Halogen and chalcogen bonding interactions, first exploited by Matile and coworkers in the context of anion transport across membranes, have been shown to favour chloride over hydroxide ion transport. Due to their higher lipophilicity and increased directionality compared to hydrogen bonds, halogen bonds have proven particularly advantageous for developing active ionophores. For example, we have reported bidentate iodotriazole and telluromethyltriazole halogen and chalcogen bonding anionophores, whilst Valkenier and coworkers reported an iodotriazole functionalised calix [6]arene derivative that exhibits Cl ->OH -/H + selectivity. Another strategy to enhance such chloride selectivity is to increase the encapsulation of the anion binding site (Figure , bottom), as exemplified by Davis' macrocyclic cholaphane derivatives, although the precise origins of this selectivity remain to be fully understood. Size complementarity and ion solvation are crucial factors in the design of a selective transporter. For example, the oligodepsipeptide macrocyclic ionophore valinomycin exhibits remarkable selectivity for K + over Na + , which arises from a high degree of size complementarity between K + and the valinomycin binding site. Similarly, the size difference between chloride and hydroxide ions (ionic radii of 1.8 and 1.1 Å, respectively ) could, in principle, be exploited to enhance the selective binding of one over the other. On the other hand, as previously suggested by Wu et al. , differences in ion solvation also affect selectivity. Hydroxide has a significantly larger hydration free energy compared to chloride (-105.0 vs -74.6 kcal mol -1 ), meaning that a more encapsulating binding site that promotes a greater degree of anion desolvation would disfavour OH -binding in aqueous media in competition with Cl -. Increasing the degree of encapsulation of the bound anion, and hence the degree of anion desolvation, may therefore serve to maximise this discrimination, given that it has been shown that ion transport is typically also accompanied by the co-transport of water associated with the ion solvation shell. Here, we report the synthesis and characterisation of a halogen-bonding macrocyclic transporter family that exhibits unprecedented Cl ->OH -/H + anion transport selectivity. Building upon our previously developed bidentate iodotriazole halogen bonding anionophore scaffold, which exhibited high activity but moderate anion selectivity (compound 1) , we developed a series of conformationally preorganised macrocycles, compounds 2-6, employing convergent halogen bond donors for anion recognition (Figure ). The best performing macrocyclic transporter 2 exhibits record selectivity for chloride over hydroxide in vesicle assays, representing almost two orders of magnitude improvement over the non-macrocyclic analogue 1. Density functional theory (DFT) and molecular dynamics (MD) simulations show that the origin of this selectivity arises from a reduced energetic penalty and a lower desolvation cost upon binding of the chloride anion compared to hydroxide.