As a result, it turns out that macrocycle 2 exhibits the highest affinity of the three macrocycles, regardless of the size of the anion (Table ). It even outperforms for both Cl -and H2PO4 -, the similarly sized tetraurea macrocycles. For macrocycle 3 the lower affinity for the different guests can be explained by the need to outcompete the intramolecular hydrogen bonds that can form in this flexible macrocycle, that has furthermore only two aromatic CH protons pointing into the cavity. The difference in affinities between macrocycle 1 and 2 for Cl -and H2PO4 - could be explained by their difference in flexibility. Both these anions are expected to be too small for macrocycle 1 to optimally exploit all its H-bond donors, whereas macrocycle 2 is most likely able to adapt its conformation so that all four NH H-bond donors can be engaged with each of the anions. More surprising was the fact that macrocycle 2 also outperformed macrocycle 1 in binding H2P2O7 2- by three orders of magnitude, since macrocycle 1 was expected to be well preorganized for binding of such larger guests, based on initial computational studies. As amides were reported to have slightly higher anion binding affinities than acylhydrazones and calculated to be slightly more acidic (see SI Section 1), the difference in binding motifs cannot explain the superior binding by 2. However, the presence of six CH protons pointing into the cavity of 2 compared to four 4 CH protons for 1 could contribute to its performance.