To rationalize our results, we have decomposed the interaction per ligand in each cluster, finding that the interaction with Zn(II) is stronger for acetate ligands than for imidazole. However, the higher energetic cost of incorporating negatively charged acetates in a given coordination shell attenuates these differences, especially in tetrahedral clusters. As a result, in tetrahedral environments, the average stabilization of an acetate and an imidazole ligand is very similar. Besides, when there is a mixture of acetate/imidazole ligands in the coordination shell, there is a slight preference for acetates when the number of acetates decreases in the coordination shell. This is the case for [Zn(Im) 3 (Ac) 1 ] + cluster in tetrahedral environments. This fact explains the propensity for Zn(II) to coordinate a combination of histidine and Asp/Glu in protein environments.