As anticipated, iodine-anion distances are larger (by an average of 0.6 Å) for the Cl -complexes than in OH -complexes, which is consistent with the higher charge density of the latter. The calculated binding energy differences (Figure and) show that all transporters preferentially bind OH -over Cl -; however, this preference decreases from the acyclic 1 (ΔE = -14.3 kcal mol -1 ) to the macrocycles 2 and 4 (ΔE = -12.4 and -12.6 kcal mol -1 ) and to a lesser extent for the larger macrocycle 3 (ΔE = -13.1 kcal mol -1 ). The binding energies can be further broken down into a distortion component, representing the energy required to adopt the bound conformation, and an interaction component, which reflects the ion-transporter interactions. This analysis shows that interaction energy, rather than distortion, drives the changes in OH -binding preference. Analysis of the free energy of binding shows a more marked decrease in OH -binding preference when comparing acyclic and cyclic transporters (Figure ). This arises from both a reduced enthalpic preference of OH -binding, from 1 (-6.7 kcal mol -1 ) to 2, 4 (-4.0 and -4.1 kcal mol -1 ) and 3 (-5.1 kcal mol -1 ) and to a lesser extent entropic contributions, leading to an overall reduction of over 3 kcal mol -1 for OH⁻ binding preference in the cyclic transporters.