Studies of nitric oxide interaction with mono- and dinuclear copper(ii) complexes of prion protein bis-octarepeat fragments

Abstract

The interaction of nitric oxide with copper(II) complexes of two octarepeat sequences belonging to the prion protein was studied, considering both mononuclear and dinuclear systems, i.e. Cu–Ac-(PHGGGWGQ)₂-NH₂ and Cu₂–Ac-(PHGGGWGQ)₂-NH₂, respectively. The NO interaction with both systems was followed in aqueous solutions at physiological pH value, by using UV-Vis and EPR spectroscopic techniques as well as cyclic voltammetry. The mechanism of NO interaction with the mononuclear copper complex can be considered similar to that previously observed for the analogous copper systems with Ac-HGGG-NH₂ and Ac-PHGGGWGQ-NH₂. A more complicated behaviour was found with the copper dinuclear system, in which the involvement of two different intermediate complex species was evidenced. A positive cooperativity between the two copper ions, in the reduction process was inferred. When working with a large excess of the Ac-(PHGGGWGQ)₂-NH₂ ligand, the frozen-solution EPR parameters pertain to the well characterized [Cu(N_im)₄]²⁺ unit, which did not exhibit any interaction with NO. The presence of a free coordination site is the necessary requirement for the NO interaction to occur, as found only in the square-pyramidal geometry of [Cu(L)H₋₂] or [Cu₂(L)H₋₄] complex species, which form when copper and ligand concentrations are similar.