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

The ligand piperazine-1,4-bis[4-(N-(1-acetoxy-3-(1-methyl-1H-imidazol-4-yl) )-2-propyl)-N-(1-methyl-1H-imidazol-2-ylmethyl)aminobutyl] (PHI) was synthe sized by a multistep procedure starting from N-T-methyl-L-histidine, pipera zine-l,4-bis[4-(4-oxo-4-butanoic) acid] and 1-methyl-1H-imidazole-2-carbald ehyde. This ligand has two potential tridentate, aminobis(imidazole) (A sit es), and one bidentate, piperazine (B site), binding sites for metal ions a nd was employed for the synthesis of the binuclear [Cu2PHI](4+) and the tri nuclear [Cu3PHI](6+) complexes, the latter of which features a coordination environment mimicking that present in the trinuclear dusters of the blue c opper oxidases, For comparison purposes, the mononucleating ligand L-N-alph a-(1-methyl-1H-imidazol-2-ylmethyl)-N-T-methylhistidine methyl ester (IH) a nd its complex [CuIH](2+) have been also prepared. These copper(II) model c omplexes are the first reported which are directly derived from chiral L-hi stidine 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. Thi s arrangement implies the adoption of an unusual conformation of lambda chi rality by the L-histidine residue and is determined by the attempts to mini mize steric interference between the substituents at the tertiary amine don or group and the histidine residue bearing the C-alpha substituent acetoxym ethylene group of the bound PHI ligand. For the less sterically crowded sec ondary amine group of the bound IH ligand, the histidine C-ce substituent c an occupy a pseudoaxial position, so that in the complex [CuIH](2+) the 'no rmal' arrangement with three equatorial nitrogen donors and delta chirality in the L-histidine chelate ring occurs. (C) 1999 Elsevier Science Ltd. All rights reserved.