A DFT study of isolated histidine interactions with metal ions (Ni²⁺, Cu²⁺, Zn²⁺) in a six-coordinated octahedral...

Understanding the role that metal ions play in biological and material processes is critical to addressing a number of diseases and problems facing society today. There have been a number of studies that have begun to approach this concern from a myriad of different perspectives. However, there is still a considerable lack of understanding concerning the mechanisms and structures of metal-related problems, specifically biological and medical-related issues. Understanding the mechanism of ingestion and uptake of metals into the human body is critical to addressing many diseases such as Alzheimer's and certain types of cancers. Using computational techniques, this work adds to the overall understanding of metal interactions with proteins by focusing on metal ion interactions with the amino acid, histidine, one of the most common sites of metal attachment. In this work, the geometries of single and dual histidines attached to Ni²⁺, Cu²⁺, and Zn²⁺ ions at B3LYP/6-311G(d) are presented. The results show stable octahedral complexes associated with each of the metal ions. Free energy calculations suggest that all three complexes are spontaneous in the formation of the dual histidine-metal complexes. Nickel and copper are spontaneous in the formation of the single histidine complex, although the copper complex undergoes slight geometric changes. Zinc is found to be nonspontaneous in forming the single histidine complex. Finally, the reduction potential of the single histidine-metal complex is presented. All of the complexes show positive reduction potentials. However, the nickel and copper complexes undergo geometrical changes to adopt a square planar conformation. Graphical abstract The impact of metal ions in biological systems is of great importance to understanding a diverse number of diseases. By understanding the fundamentals of select ions complexed with histidines, greater understanding of the mechanisms of actions these ions play in health may be elucidated. This work presents initial structures and thermodynamics of histidine complexes with nickel, copper, and zinc metal ions.