Single crystals of suitable quality for X-ray diffraction (XRD) analysis were obtained from compounds 1, 3 and 4, under conditions that were very similar to the hydrogels, suggesting similar packing in the two phases, as supported by powder XRD data on xerogels. In particular, compounds 1 and 3 formed supramolecular water-channels, albeit with significantly differing inner diameters (i.e., 1.0 nm and 0.5 nm) as they were defined by 6 and 4 peptide molecules, respectively (Fig. ). This is in marked contrast with analogs with Leu instead of Nle, which packed to form water-channels with a diameter defined by 4 peptide molecules, regardless of the order of amino acids along the sequence. Compound 1 crystallizes in a monoclinic system (P21 space group), while compound 3 in a tetragonal system (P41 space group). Interestingly, the asymmetric unit in crystal structure of 1 has three independent molecules with a pseudo-six-fold axis symmetry (see ESI Section S9 for details). Furthermore, because of highly disordered water molecules, we opted to use a solvent mask in the refinement procedure of 1. The two crystal structures show the typical supramolecular arrangement of the Phe-Phe class described by Görbitz, with the dipeptides arranged head-to-tail to define the hydrophilic water channels parallel to the shortest axis and the side chains segregated into the hydrophobic region.