The intramolecular hydrogen bonding observed for macrocycle 3, both by modelling (Figure ) and by X-ray crystallography (Figure ), probably explains the poor interaction of this macrocycle with Cl -. The lower affinity of macrocycle 1 for Cl -, compared to macrocycle 2, can be explained by the fact that only one of the dipicolinic bisamide motifs is able to interact with Cl -(Figure ). Thus, the affinity of 1 was found to be within the same order of magnitude, albeit slightly higher, as that observed for dipicolinic bisamides with less preorganization (10-47 M - 1 ), but significantly lower than that of more flexible dipicolinic bisamide macrocycles (1930 M -1 , in DMSO-d6). More surprising, however, was the fact that macrocycle 2 exhibits a high affinity for Cl -compared to, for example, the macrocycles of the same size utilizing four ureas as the binding motifs (up to 500 M -1 , in DMSO-d6), which could have been expected to provide higher affinities than acylhydrazones. During the 1 H-NMR titrations of macrocycle 1 in DMSO (0.5% H2O) with H2PO4 -and H2P2O7 2-the signals showed significant broadening after addition of 1-2 equivalents of the salts, preventing a reliable quantification of the binding (Figures ). Additionally, precipitation was observed after addition of 1 equivalent of the salts, further complicating the binding studies. The NH signal of macrocycle 3 also broadened upon addition of H2PO4 -and H2P2O7 2-, while the other signals showed only minimal changes with up to 5 eq. of these salts (Figures ).