Tailoring Antioxidant Activities: Metal-Type Dependent, Highly Active SOD or Catalase Mimetics

The failure of the therapeutic administration of superoxide dismutase (SOD) and catalase (CAT) enzymes to prevent oxidative stress has fostered the development of metal complexes that are capable of mimicking their activity. In the present work, two new pyridine azacyclophane ligands capable of coordinating Cu²⁺ and Fe²⁺ to give rise to mimetics with high activities toward disproportionation of the superoxide anion or hydrogen peroxide, depending on the metal ion, have been prepared. Although the Cu²⁺ complexes have some of the highest SOD activities reported to date, they are completely inactive toward H₂O₂ disproportionation. In contrast, the Fe²⁺ complexes catalyze the disproportionation of H₂O₂ without showing any catalytic SOD activity. Therefore, the type of antioxidant activity of these macrocycles is dictated by the nature of the metal ion, which represents a new approach to the development of potentially useful mimetics.

Reactive oxygen species (ROS) like superoxide and hydrogen peroxide play both beneficial and harmful roles in biology, but their excess causes oxidative stress, which is linked to diseases such as cancer, diabetes, and neurodegeneration. To address the limitations of natural superoxide dismutase (SOD) and catalase (CAT) enzymes, two new pyridine azacyclophane ligands were developed that selectively coordinate Cu²⁺ (for superoxide dismutation) and Fe²⁺ (for hydrogen peroxide decomposition), offering a tunable antioxidant strategy with promising therapeutic potential.