Copper(II) complexes with cyclo(L-aspartyl-L-aspartyl) and cyclo(L-glutamyl-L-glutamyl) derivatives and their antioxidant properties

Abstract

Two new functionalized cyclodipeptides have been synthesized with the aim of obtaining a good model of superoxide dismutase. Better to mimic the active site of this metalloenzyme, these two compounds have been designed to allow a great co-ordination flexibility. Copper(II) complexes with cyclo(-L-aspartyl-L-aspartyl-) or cyclo(-L-glutamyl-L-glutamyl-)bis(histamine)(L) have been thermodynamically and spectroscopically characterized and their antioxidant activity tested against enzymatically generated O₂^–. Taking into account the speciation of the system, it has been determined that the more active species against O₂^– is the [CuL₂]²⁺ complex. Electron spin resonance measurements suggest for this species the presence of four imidazole nitrogen atoms in a slightly tetrahedrally distorted co-ordination plane. The [CuLH_–2] complex species also possesses four-nitrogen co-ordination involving two deprotonated peptide nitrogen atoms. The complex [CuL₂]²⁺ showed the highest antioxidant activity and reasons for this behaviour are proposed on the basis of spectroscopic and voltammetric data.