The macrocyclic effect follows the same principle as the chelate effect, but the effect is further enhanced by the cyclic conformation of the ligand. Macrocyclic ligands are not only multi-dentate, but because they are covalently constrained to their cyclic form, they allow less conformational freedom. The ligand is said to be "pre-organized" for binding, and there is little entropy penalty for wrapping it around the metal ion. For example heme b is a tetradentate cyclic ligand which is strongly complexes transition metal ions, including (in biological systems) Fe⁺².

Figure 4

: (left) A free, unbound porphorin ligand and (right) Heme b macrocyclic ligand that binds iron in hemoglobin

Some other common chelating and cyclic ligands are shown below: