Title:

Evaluation of Iron Chelators for the Prevention of Fenton Chemistry

Intracellular free iron catalyzes hydroxyl radical (•OH) formation via Fenton-like reactions, contributing to oxidative stress and diseases, including cancer, neurodegeneration, and cardiovascular disease. Iron chelators represent a promising therapeutic strategy for limiting •OH production, though evaluating their effectiveness requires reliable assays that approximate intracellular conditions. Here we report the evaluation of three iron chelators — Propox, OHQ, and EDTA — using the deoxyribose assay, a colorimetric method in which absorbance at 532 nm serves as a measure of •OH production. Propox demonstrated significantly greater inhibition of •OH production than both OHQ and the EDTA control, establishing it as a strong therapeutic candidate. To probe the mechanism of iron-catalyzed •OH production, we validated the azide assay as a reliable method for detecting open coordination sites in iron-chelator complexes. Ongoing work in the Planalp Lab is focused on developing water-soluble Propox derivatives to enable conclusive azide assay results and improve therapeutic viability.

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