Copper Complexation by Amino Acid: l-Glutamine–Copper(II)–l-Histidine Ternary System

Abstract Menkes disease is a lethal genetic disorder of copper transport in humans. Its current treatment is the administration of copper–l-histidine complex. However, this therapy is only effective in some cases and when started early in life. In order to develop an improved treatment, copper(II) mixed ligand amino acid complexes were studied because these complexes play an important role in the physiological copper pathway. A promising strategy is the administration of l-histidine–copper(II)–l-glutamine complex, which has been reported to be the predominant low molecular-weight copper(II) complex in human blood serum. Before the biopharmaceutical studies of l-histidine–copper(II)–l-glutamine complex, a physicochemical study of this ternary system must be performed. The stoichiometry and the stability of l-histidine–copper(II)–l-glutamine relative to copper(II)–l-histidine and copper(II)–l-glutamine were established at pH 7 in solution by polarography and UV–visible spectroscopy. Nevertheless, it has been demonstrated that the species [Cu(His)2] and [Cu(His)2(OH)] coexist in the same solution. This study has been complemented by EPR analysis which suggests copper in [Cu(His)(Gln)] complex has a distorted octahedral geometry. The first shell of copper coordination is 3 N, 1 O, histidine, and glutarnine being bidentate.