Enhancement of the Water Affinity of Histidine by Zinc and Copper Ions

Histidine (His) is widely involved in the structure and function of biomolecules. Transitionmetal ions, such as Zn2+ and Cu2+, widely exist in biological environments, and they are crucial to many life-sustaining physiological processes. Herein, by employing density function calculations, we theoretically show that the water affinity of His can be enhanced by the strong cation-pi interaction between His and Zn2+ and Cu2+. Further, the solubility of His is experimentally demonstrated to be greatly enhanced in ZnCl2 and CuCl2 solutions. The existence of cation-pi interaction is demonstrated by fluorescence, ultraviolet (UV) spectroscopy and nuclear magnetic resonance (NMR) experiments. These findings are of great importance for the bioavailability of aromatic drugs and provide new insight for understanding the physiological functions of transition metal ions.

Automated summary

In this study, the effect of cation-pi interaction between histidine and zinc ions and copper ions on the water affinity of histidine was investigated. It was theoretically shown that the cation-pi interaction can enhance the water affinity of histidine, which was experimentally demonstrated by the increased solubility of histidine in zinc chloride and copper chloride solutions. The existence of cation-pi interaction was further confirmed by fluorescence, UV spectroscopy, and NMR experiments. These findings are of great importance for the bioavailability of aromatic drugs and provide new insights into the physiological functions of transition metal ions.