Pourbaix Stability Field Mapping of Ferrihydrite-Catalyzed PLOOH Production

Ferroptosis is a form of programmed cell death where iron goes rogue — it reacts with fats in cell membranes, creating toxic lipid peroxides that essentially oxidize the cell from the inside out. Understanding precisely *when* iron becomes dangerous is crucial for diseases like cancer, neurodegeneration, and organ injury. Meanwhile, serpentinization is a deep-Earth geological process where water reacts with rock, producing hydrogen gas and highly reactive iron chemistry — a process geochemists map using something called a Pourbaix diagram, which is essentially a 2D map that tells you which form iron takes at any given acidity (pH) and electrical charge environment (Eh, a measure of oxidizing vs. reducing conditions). The hypothesis proposes borrowing this geological tool — the Pourbaix diagram — to predict ferroptosis chemistry in biology. Specifically, it suggests that the toxic lipid peroxides (PLOOHs) that trigger cell death are only produced when iron exists in a particular dissolved form (Fe²⁺, the ferrous ion), and that this happens in a very specific zone of pH and Eh conditions. The idea is to build a 5×5 grid of lab experiments covering different acidity and redox conditions, mix iron nanoparticles with fat molecules mimicking cell membranes, and see if the resulting damage map lines up with the iron stability zones predicted by the geological diagram. A clever supporting insight: the fact that iron stays stubbornly locked up at neutral pH (like in most of the cell) actually explains *why* ferroptosis requires the acidic environment of lysosomes — the cell's recycling compartments — to release dangerous iron in the first place. This is a genuinely cross-disciplinary idea, pulling a tool from Earth science and applying it to cell biology. The Pourbaix diagram has been used for over 70 years to understand corrosion and mining chemistry, but almost never to map biological iron toxicity. If the overlap holds, it would mean geochemical theory can predict cellular iron danger zones with unusual precision.

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