We summarize our results in Fig. . Altogether, these results reveal a strong metal-ligand coordination number dependence on the thermodynamic binding affinity of imidazole and histamine-M 2+ complexes, in which the hierarchy of binding affinities are dictated by the coordination number of the complexes formed under different stoichiometric conditions. This hierarchy is particularly driven by the tendency of Ni 2+ to form ML3 or ML4 complexes with histamine and imidazole, respectively, suggesting that Ni 2+ binding dictates in systems where the formation of complexes with larger coordination numbers is allowed, whereas Cu 2+ binding dictates in systems where primarily bis complexes are formed. This might provide insight into the preferred binding state of histidine-M 2+ complexes in biological systems; for instance, the in vivo binding of M 2+ in H. pylori in which Ni 2+ dominates the metal-binding hierarchy may be a result of the stoichiometric binding of the transition metals with histamine or imidazole in a ratio greater than 2 (i.e., ML3 or higher), whereas the in vitro binding may be dominated by ML2 complexes in which Cu 2+ exhibits the greatest affinity to histamine or imidazole.