New Insights into the Coordination Chemistry and Molecular Structure of Copper(II) Histidine Complexes in Aqueous Solutions

Aqueous solutions of Cu²⁺/histidine (his) (1:2) have been analyzed in parallel with infrared, Raman, ultraviolet/visible/near-infrared, electron spin resonance, and X-ray absorption spectroscopy in the pH range from 0 to 10. Comprehensive interpretation of the data has been used to extract complementary structural information in order to determine the relative abundance of the different complexes. The formation of six different, partly coexisting species is proposed. Structural proposals from literature have been unambiguously confirmed, refined, or, in several cases, corrected. At highly acidic conditions, Cu²⁺ and his are present as free ions, but around pH = 2, coordination starts via the deprotonated carboxylic acid group. This results in the intermediate species Cu²⁺[H₃his⁺(O_c)] and Cu²⁺[H₃his⁺(O_c)]₂. The coordination via O_c is attended with a drop in the pK_a value of the other receptor groups resulting in a concomitant conversion to the bidentates Cu²⁺[H₂his⁰(O_c,N_am)] and Cu²⁺[H₂his⁰(O_c,N_am)]₂, with the latter being dominant at pH = 3.5. Coordination of the imidazole ring begins around pH = 3 and leads to the formation of the mixed ligand complexes Cu²⁺[H₂his⁰(O_c,N_am)][Hhis^-(O_c,N_am,N_im)] and Cu²⁺[Hhis^-(N_am,N_im)][Hhis^-(O_c,N_am,N_im)] around pH = 5. It is demonstrated that coordination of the imidazole ring occurs predominantly via the N^π atom. At pH > 7, the double-tridentate ligand complex Cu²⁺[Hhis^-(O_c,N_am,N_im)]₂ is the major species with the N atoms in the equatorial plane and the O atoms in the axial position. This complex decomposes at pH > 10 into a copper oxide/hydroxide precipitate. The overall results provide a consistent picture of the mechanism that drives the coordination and complex formation of the Cu²⁺/his system.