Interaction between Histidine and Zn(II) Metal Ions over a Wide pH as Revealed by Solid-State NMR Spectroscopy and DFT Calculations

The interactions between histidine and metal species play essential roles in a wide range of important biological processes including enzymes catalysis and signal transduction. In this work, solid-state NMR techniques were employed to determine the interaction between histidine and Zn­(II) from pH 3.5 to 14. 2D homo- and heteronuclear correlation NMR experiments were utilized to extract the <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N chemical shifts in various histidine–Zn­(II) binding complexes. Several histidine–Zn­(II) binding models were proposed on the basis of experimental results as well as DFT theoretical calculations. No direct interaction could be found between biprotonated histidine and Zn­(II) at acidic pH. At pH 7.5, one zinc ion could be hexa-coordinated with two histidine molecules on C′, N<sub>α</sub> and deprotonated N<sub>δ1</sub> sites. As the pH increases to 11–14, both of the N<sub>δ1</sub> and N<sub>ε2</sub> sites could be deprotonated as acceptors to be bound to either Zn­(II) or water. All of these findings give a comprehensive set of benchmark values for NMR parameters and structural geometries in variable histidine–Zn­(II) binding complexes over a wide pH range and might provide insights into the structure–property relationship of histidine–metal complexes in biological metalloproteins.