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

Histidine (His) is widely involved in the structure and function of biomolecules. Transition-metal ions, such as Zn(2+) and Cu(2+), 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–π interaction between His and Zn(2+) and Cu(2+). Further, the solubility of His is experimentally demonstrated to be greatly enhanced in ZnCl(2) and CuCl(2) solutions. The existence of cation–π 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.