Radical Chemistry and Oxidative Cell Death Mechanisms

Radical chemistry underpins many of the fundamental reactions that drive oxidative stress in biological systems. Reactive oxygen species (ROS), such as superoxide and hydroxyl radicals, initiate chain reactions that propagate lipid peroxidation, protein damage and DNA strand scission. Antioxidant defences—including enzymatic systems like superoxide dismutase and catalytic radical‐trapping molecules—serve to intercept radicals and limit the spread of oxidative injury. When this balance is disrupted, regulated forms of cell death emerge. Ferroptosis, for example, is characterised by iron‐dependent lipid peroxide accumulation and membrane damage. Other pathways, including apoptosis and necroptosis, may also be triggered by radical overload, mitochondrial dysfunction and perturbation of redox‐sensitive signalling networks. The interplay between radical generation, antioxidant capacity and cell death decisions is central to diverse pathologies, ranging from neurodegeneration and ischaemia–reperfusion injury to cancer therapy resistance. Advances in chemical tools and imaging approaches have begun to reveal the kinetics of radical–molecule interactions in situ and to identify novel small molecules capable of modulating oxidative cell death pathways for therapeutic benefit.

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Radical Chemistry and Oxidative Cell Death Mechanisms publication trend

The graph below shows the total number of articles in radical chemistry and oxidative cell death mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Highly reactive oxygen‐containing molecules that can initiate chain reactions leading to oxidative damage.

Peroxyl radical: An oxygen-centred radical (ROO•) formed when molecular oxygen reacts with a carbon-centred radical, driving lipid peroxidation chains.

Lipid peroxidation: A free-radical-mediated process in which membrane lipids are oxidised, compromising membrane integrity and cell viability.

Ferroptosis: A regulated form of cell death dependent on iron and characterised by lethal accumulation of lipid peroxides.

Antioxidant: A molecule that donates electrons or hydrogen atoms to neutralise radicals, thereby terminating chain reactions and protecting biomolecules.

References

1. Lipid Peroxidation and Antioxidant Protection. Biomolecules (2023).
2. Nitroxides as Building Blocks for Nanoantioxidants. ACS Applied Materials & Interfaces (2021).
3. Ferroptosis and multi-organ complications in COVID-19: mechanisms and potential therapies. Frontiers in Genetics (2023).