Transporters 2, 3 and 4 proved to be highly active chloride transporters, with EC50 values for chloride transport (determined in the presence of FCCP) of 34, 68 and 50 nM, respectively. Interestingly, the enhanced chloride binding capability of 3 determined from titration experiments did not result in a higher chloride transport activity. We suggest that the larger size (1,4-bishexylvs bis-pentyl-benzene linkers) may counter the enhanced binding by slowing down membrane translocation. The best performing transporter was 2, with an EC50 of 34 nM in the presence of FCCP. This represents a modest decrease in activity compared to the parent transporter 1 (3 nM with FCCP), but this is more than compensated by the observed selectivity. Macrocycles 2-4 exhibited low activity for OH -transport (in the absence of FCCP) which prevented a quantitative measure of S, because low solubility at the necessary high concentrations meant that an entire dose response curve could not be obtained. Therefore, we used the activity at 10 µM transporter (the solubility limit) to determine a lower bound of the selectivity, which revealed that the halogen bonding macrocycles exhibit almost two orders of magnitude higher selectivity compared to 1 (S of 5.3), with S > 300 for the most active transporter 2 (Table ). Transporters 5 and 6 were inactive both in the presence and the absence of FCCP, despite macrocycle 5 being one of the stronger Cl -receptors in solution. Compounds 5 and 6 are the most lipophilic of the family of macrocycles (clogP of 6.55 and 6.62, Table ), which may contribute to the observed inactivity, in addition to the weak binding of chloride by 6.