Enhancement of metal‐binding affinity for Cu+/Cu2+ complexes by hydrogen bond network

Using density functional theory, polyols were used as model ligands for Cu+/Cu2+ complexes to study the role of the hydrogen bond network on the metal binding affinity. In addition to the gas phase studies, the calculations were performed in 1‐decanol and DMSO solvents. The Cu2+ complexes were the most stable complexes with the highest bond dissociation energies (BDE). The presence of three H‐bonds in the first shell increased BDE values up to 17.99 and 57.07 kcal/mol for Cu+ and Cu2+ complexes in the gas phase, respectively, whereas the presence of another three H‐bonds in the second shell increased BDE values up to 7.27 and 24.35 kcal/mol for Cu+ and Cu2+ complexes in the gas phase, respectively. Therefore, this H‐bond network caused, for example, a more stable Cu+ complex with a formation constant of 1.4 × 1017 times. The natural bond orbital (NBO), atoms in molecules (AIM), and reduced density gradient (RDG) analyses showed that the intramolecular hydrogen bond network led to the enhancement of metal‐binding affinity. The calculated BDE values for the studied Cu+/Cu2+ complexes of some polyols, with different number of OH groups, showed that the intramolecular hydrogen bond network enhances the metal binding affinity. The overall effect of an H‐bond network containing six H‐bonds in the Cu+ complex was the change of the formation constant of the complex up to 1.4 × 1017 times. The results of this work can help manipulate ligands and metal cations when designing metalloproteins.