Functional mimics of copper enzymes. Synthesis and stereochemical properties of the copper(II) complexes of a trinucleating ligand derived from l-histidine

Abstract

The ligand piperazine-1,4-bis[4-( N-(1-acetoxy-3-(1-methyl-1 H-imidazol-4-yl))-2-propyl)- N-(1-methyl-1 H-imidazol-2-ylmethyl)aminobutyl] (PHI) was synthesized by a multistep procedure starting from N τ-methyl- l-histidine, piperazine-1,4-bis[4-(4-oxo-4-butanoic) acid] and 1-methyl-1 H-imidazole-2-carbaldehyde. This ligand has two potential tridentate, aminobis(imidazole) (A sites), and one bidentate, piperazine (B site), binding sites for metal ions and was employed for the synthesis of the binuclear [Cu 2PHI] 4+ and the trinuclear [Cu 3PHI] 6+ complexes, the latter of which features a coordination environment mimicking that present in the trinuclear clusters of the blue copper oxidases. For comparison purposes, the mononucleating ligand l- N α-(1-methyl-1 H-imidazol-2-ylmethyl)- N τ-methylhistidine methyl ester (IH) and its complex [CuIH] 2+ have been also prepared. These copper(II) model complexes are the first reported which are directly derived from chiral l-histidine residues. A detailed analysis of the UV–vis, CD and EPR spectra of the complexes has established that the Cu(II) centers bound to PHI A sites are square-pyramidal in solution, with the amino and one imidazole donor in the equatorial plane and the additional imidazole group bound axially. This arrangement implies the adoption of an unusual conformation of λ chirality by the l-histidine residue and is determined by the attempts to minimize steric interference between the substituents at the tertiary amine donor group and the histidine residue bearing the C-α substituent acetoxymethylene group of the bound PHI ligand. For the less sterically crowded secondary amine group of the bound IH ligand, the histidine C-α substituent can occupy a pseudoaxial position, so that in the complex [CuIH] 2+ the `normal' arrangement with three equatorial nitrogen donors and δ chirality in the l-histidine chelate ring occurs.