Synthetic analogue approach to metallobleomycins: syntheses, structure and properties of mononuclear and tetranuclear gallium(III) complexes of a ligand that resembles the metal-binding site of bleomycin

Abstract

As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the peptide ligand N-(2-(4-imidazolyl)ethyl)pyridine-2-carboxamide (pypepH 2) resembling a fragment of the metal-binding domain of bleomycins (BLMs), have been isolated. Reaction of pypepH 2 with (Et 4N)[GaCl 4] and Ga(acac) 3 [acac − is the acetylacetonate(−1) ion] affords the mononuclear complex [Ga(pypepH) 2]Cl · 2H 2O ( 1) and the tetranuclear complex [Ga 4(acac) 4(pypep) 4] · 4.4H 2O ( 2), respectively. Both complexes were characterized by single-crystal X-ray crystallography, IR spectroscopy and thermal decomposition data. The pypepH − ion in 1 behaves as a N(pyridyl), N(deprotonated amide), N(pyridine-type imidazole) chelating ligand. The doubly deprotonated pypep 2− ion in 2 behaves as a N(pyridyl), N(deprotonated amide), N(imidazolate), N′(imidazolate) μ 2 ligand and binds to one Ga III atom at its pyridyl, amide and one of the imidazolate nitrogens, and to a second metal ion at the other imidazolate nitrogen; a chelating acac − ligand completes six coordination at each Ga III centre. The IR data are discussed in terms of the nature of bonding and known structures. The 1H NMR spectrum of 1 suggests that the cation of the complex maintains its integrity in dimethylsulfoxide (DMSO) solution. Complexes 1 and 2 are the first synthetic analogues of metallobleomycins with gallium(III).