Novel Reactions of Nickel (II) - Oligopeptide Complexes with Dioxygen Species

Abstract

The ability of simple oligopeptide complexes of nickel (II) to react with various dioxygen intermediates was investigated. Under physiological conditions, nickel (II)-histidine-containing oligopeptides were found to dismutate superoxide anions and disproportionate hydrogen peroxide. In the latter process, chemiluminescence was generated and a strongly oxidizing intermediate was detected capable of oxidizing uric acid, hydroxylating p-nitrophenol, and damaging 2-deoxy-D-ribose. The generation of this reactive intermediate likely occurs without the involvement of free hydroxyl radicals derived from Haber-Weiss or Fenton-type reactions. In addition, the Ni(II) complex of glycylglycyl-L-histidine (GGH) was found to react with mollecular oxygen resulting in the oxidation of the ligand. An attempt was made to relate these reactions to the involvement: of the nickel(III)/(II) redox couple which was shown to exist under physiological conditions. Similar reactivity was observed for non-histidine-containing oligopeptides but higher pH values were required. The oligopeptides used not only represent biologically relevant ligands but: the histidine containing oligopeptides mimics the specific copper(II)/nickel(II) binding and transport site of human serum albumin. The observations made in this study suggest some novel mechanism for the deleterious effects associated with excessive lifelong exposure to nickel compounds, especially in relation to cancer of the respiratory tract.