On the structure of manganese (II)- and copper (II)-histidine complexes

l-Histidine offers three groups as potential binding sites for metal ions: the imidazole, amino, and carboxylic acid groups. For stereochemical and geometric reasons, Cu(II) can bind strongly to only two of the three groups at a given moment. There is a contradiction in the literature as to which of the three groups coordinate with the coordination square of Cu(II). On the one hand, it has been suggested that the deprotonated ligand coordinates at the imidazole and the amino group, and on the other hand with the amino and the carboxylic acid function. Most of the evidence presented for one or the other possibility derives from indirect methods; e.g., the determination of stability constants. Since evidence has been given that only those groups are oxidized by H2O2 which are in the coordination sphere of Cu(II), this peroxidase-like “probe” was used to investigate 1:1 molar mixtures of Cu(II) and l-histidine or histamine. The results suggested that l-histidine forms a histamine-like complex with Cu(II). NMR spectra of l-histidine and histamine taken in D2O with increasing amounts of Cu(II), under conditions where Cu(II) 1:2 complexes are formed quantitatively, show also that the imidazole group is involved in the formation of the Cu(II)-histidine 1:2 complex. The NMR spectra of Mn(II) complexes were investigated for the same ligands as with Cu(II). The results show that Mn(II) interacts more strongly with histidine than with histamine, in agreement with estimates of the degree of complex formation. All three binding sites of histidine can bind to Mn(II). The structures of the several species of l-histidine complexes are discussed, as are the known stability and acidity constants. The pH regions in which the protonated species transform to the deprotonated ones are mentioned, as are the structures of some known mixed; i.e., ternary, l-histidine Cu(II)-amino acid complexes.