Co-ordinating properties of cyclopeptides. Thermodynamic and spectroscopic study on the formation of copper(II) complexes with cyclo(Gly-His)4 and cyclo(Gly-His-Gly)2 and their superoxide dismutase-like activity

Abstract

Two cyclopeptides, cyclo(Gly-His)₄ and cyclo(Gly-His-Gly)₂ were synthesized with the specific aim to form copper(II) complexes which are able to mimic the active site of superoxide dismutase. Proton and copper(II) complexes were thermodynamically characterized. The copper(II) complexes were also studied by means of optical and ESR spectroscopy to gain information on their structural features and by voltammetry to know about their redox ability. Moreover, the antioxidant activity of these complex species was tested against enzymatically generated superoxide radical. Depending on the pH value of the solution, definite complexes could be characterized, in particular [Cu{cyclo(Gly-His)₄}]²⁺ and [Cu{cyclo(Gly-His)₄}H_–2] and [Cu{cyclo(Gly-His-Gly)₂}H_–2] are the main species, which were taken into consideration to assay their antioxidant catalytic activity. The ESR studies suggested that a four-nitrogen co-ordination by means of imidazole nitrogen atoms or deprotonated peptide nitrogen atoms forms the environment around copper. At the same co-ordination level, the redox properties of these compounds parallel their scavenging abilities against O₂^– which are lower than those of other copper(II) complexes previously tested. The [Cu{cyclo(Gly-His)₄}]²⁺ complex showed higher redox potential and better catalytic ability than [Cu{cyclo(Gly-His)₄}H_–2] and [Cu{cyclo(Gly-His-Gly)₂}H_–2], which have roughly similar redox potentials and scavenging abilities.