The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of O2-

Abstract

Copper complexes of 1,10-phenanthroline and some substituted 1,10-phenanthroline cleave DNA in the presence of a reducing agent and molecular oxygen. Generally, the damage is attributed to hydroxyl radicals which are formed through the Haber-Weiss reaction. It is assumed that this reaction occurs with the ternary metal complexes with the biological target and the mechanism is defined as the "site specific mechanism." In these systems, O2- drives the cycle through the reduction of copper(II). On the other hand, these same copper complexes catalyze the dismutation of O2- and thus should protect the systems from O2- toxicity. In this article, the toxicity of these complexes is explained on kinetic grounds. A general discussion on the various factors which could cause the metal ions or their complexes to act either as protectors from O2- toxicity or as sensitizers of toxic effects of O2- is given.