Iron and ROS-generating metal complexes

Iron and ROS-generating metal complexes represent a therapeutic target category focused on the modulation of redox-active metal ions to control oxidative stress. Iron (Fe) and other metals like copper (Cu) act as catalysts in the Fenton and Haber-Weiss reactions, which generate highly reactive hydroxyl radicals from hydrogen peroxide and superoxide (Winterbourn, 1995). In diseases like hereditary hemochromatosis or thalassemia, the accumulation of a 'labile iron pool' leads to systemic oxidative damage, making iron sequestration a primary therapeutic goal (Mobarra et al., 2016). Conversely, in oncology, ROS-generating metal complexes are utilized as pro-oxidant drugs to overwhelm the antioxidant capacity of malignant cells, often inducing a specialized form of iron-dependent regulated cell death known as ferroptosis (Dixon et al., 2012). These complexes interact with drugs either through direct chelation to neutralize toxicity or by serving as the active core of metallopharmaceuticals that damage DNA and lipids (Anthony et al., 2020; Chen & Stubbe, 2005). The clinical utility of targeting these processes is balanced by the risk of non-specific oxidative damage to healthy organs, particularly the heart and liver (Mobarra et al., 2016).

Other names

Redox-active metal ionsLabile iron poolMetal-mediated ROS generatorsFenton-active metals

Modulation of redox-active metal ions to either inhibit or catalyze the production of reactive oxygen species (ROS) via Fenton and Haber-Weiss reactions, leading to the regulation of oxidative stress and iron-dependent cell death (ferroptosis) (Winterbourn, 1995; Dixon et al., 2012; Mobarra et al., 2016).