Thermodynamic and spectroscopic characterization and in vitro O2– scavenger activity of copper(II) glycyl-L-histidyl-glycyl-L-histidine complexes

Abstract

Thermodynamic and spectroscopic (electron spin resonance, electronic and circular dichroism) studies have been carried out on the complex species which exist in the copper(II)–glycyl-L-histidyl-glycyl-L-histidine (HL) system in aqueous solution. The thermodynamic results suggest the formation of three important species: [CuL]⁺, [CuH_–1L] and [CuH_–2L]^–, the first being present in the range pH 3.0–5.5, the second and third in different ratios between pH 5.5 and 7.8. The complex [CuL]⁺ has a pseudo-octahedral structure, the equatorial plane of which involves the amino group, the first peptide nitrogen, an imidazole nitrogen and a water molecule; [CuH_–1L] has the same donor atoms in the equatorial plane and the other imidazole nitrogen binds in an apical site, giving a square-pyramidal geometry. For [CuH_–2L]^–, in which a second peptide nitrogen is deprotonated, the geometry is distorted and can be considered intermediate between a square pyramid with a tetrahedrally distorted plane and a distorted trigonal bipyramid. In vitro O₂^– scavenging experiments show that the most active species is [CuH_–2L]^–. The superoxide dismutase-like activity has been rationalized by considering the geometry of the copper(II) complex species.