Metal–peptide rings form highly entangled topologically inequivalent frameworks with the same ring- and crossing-numbers

With increasing ring-crossing number ( c ), knot theory predicts an exponential increase in the number of topologically different links of these interlocking structures, even for structures with the same ring number ( n ) and c . Here, we report the selective construction of two topologies of 12-crossing peptide [4]catenanes ( n = 4, c = 12) from metal ions and pyridine-appended tripeptide ligands. Two of the 100 possible topologies for this structure are selectively created from related ligands in which only the tripeptide sequence is changed: one catenane has a T 2 -tetrahedral link and the other a three-crossed tetrahedral link. Crystallographic studies illustrate that a conformational difference in only one of the three peptide residues in the ligand causes the change in the structure of the final tetrahedral link. Our results thus reveal that peptide-based folding and assembly can be used for the facile bottom-up construction of 3D molecular objects containing polyhedral links.