iron ion (Fe3+ and Fe2+)

Overview

Iron ions, primarily ferric iron (Fe3+) and ferrous iron (Fe2+), are essential transition-metal species in biology and medicine. They participate in oxygen transport, electron transfer, enzymatic catalysis, mitochondrial respiration, and redox chemistry. The interconversion between Fe3+ and Fe2+ is central to iron homeostasis and to oxidative processes such as the Fenton reaction, in which Fe2+ can react with hydrogen peroxide to generate highly reactive oxygen species. Because of this chemistry, iron ions are tightly regulated in cells and tissues, and dysregulation can contribute to oxidative stress, lipid peroxidation, ferroptosis, and tissue injury.

In biomedical research, Fe3+ and Fe2+ are frequently studied both as analytes and as mechanistic drivers of disease. Fe3+ is often used in coordination chemistry, sensing, and material synthesis, while Fe2+ is commonly associated with redox cycling and ferroptotic cell death. Recent studies have examined iron ions in cancer, vascular disease, neuroprotection, environmental redox chemistry, and iron-responsive nanomaterials, highlighting their dual role as indispensable biological cofactors and potent mediators of oxidative damage.

Focus of Latest Publications

Recent publications have focused on iron ions as both functional cofactors and reactive participants in diverse chemical and biomedical systems. Several studies examined Fe2+ and Fe3+ in the context of redox cycling, coordination chemistry, and iron-dependent biological processes. In one in silico drug-design study, the catalytic Fe2+ ion of KDM4A was central to the predicted binding mode of newly designed isonicotinic acid derivatives, with molecular dynamics suggesting stable coordination to the active site. Other work used Fe3+ in coordination-based sensing and materials systems, including a fluorescence method for vitamin B6 detection and the characterization of iron oxide nanoparticles synthesized with optimized Fe3+/Fe2+ ratios for transcranial MR-guided focused ultrasound coupling media.

A major theme across the recent literature is the use of iron ions to drive or regulate ferroptosis and chemodynamic therapy. One nanoplatform combined Fe3+, Fe2+, Mn2+, tannic acid, and a miRNA-activatable DNAzyme to generate a tumor-selective autocatalytic Fenton cycle: Fe2+ converted hydrogen peroxide into hydroxyl radicals and Fe3+, while tannic acid reduced Fe3+ back to Fe2+, sustaining reactive oxygen species production. This process was governed by tumor-overexpressed microRNAs and produced selective imaging and antitumor effects in vitro and in vivo. Another study used g-C3N4 nanosheets to sequester both Fe3+ and Fe2+ as a multisite iron chelation strategy, reducing iron overload-induced ferroptosis and preserving male reproductive function through activation of the Nrf2 pathway.

Additional publications highlighted iron ions in oxidative chemistry and tumor therapy. A study of humic substances showed that original HSs and Fe3+ can drive temperature-dependent, nonphotochemical reactive oxygen species generation in bulk solutions and microdroplets, with Fe2+ formation and hydroxyl radical production increasing at higher temperatures and in interfacial microdroplet environments. In melanoma, a controlled-release system delivered neferine and Fe3+ from a metal-organic framework; the acidic tumor microenvironment triggered release, supporting ferroptosis while also suppressing PD-L1 upregulation and reversing immune evasion. Together, these studies portray iron ions as versatile targets and mediators in redox chemistry, sensing, nanomaterial design, and iron-dependent therapeutic strategies.

Key Publications

NEWJun Integrated structure-based and fragment-guided design of isonicotinic acid derivatives as potential KDM4A inhibitors: an in silico study. (Journal of computer-aided molecular design, 2026, PMID 42371179): "MD simulations revealed stable coordination between the conserved isonicotinic acid core and the catalytic Fe2+ ion, together with persistent interactions with key active-site residues."
May MicroRNA-Governed Autocatalytic Fenton Nanoplatform for Cancer-Selective Theranostics. (ACS nano, 2026, PMID 42017828): "Meanwhile, the coreleased tannic acid reduces Fe3+ back to Fe2+, establishing a self-sustaining autocatalytic Fenton cycle that drives continuous •OH generation to eradicate cancer cells."
May Temperature-Dependent ROS Generation by Humic Substance-Iron in Bulk Solutions and Microdroplets. (Environmental science & technology, 2026, PMID 42002931): "Here, we identify an overlooked abiotic, nonphotochemical pathway for ROS generation and pollutant degradation via thermally induced activation of original HSs and Fe3+ in both bulk solutions and microdroplets at environmentally relevant temperatures."
May g-C3N4 Nanosheets as a Ferroptosis-Targeted Nanoprobe: Mitigating Iron Overload and Restoring Male Fertility via Nrf2 Pathway Activation. (Molecular pharmaceutics, 2026, PMID 41964938): "The g-C3N4 nanosheets enable specific iron ion (Fe3+ and Fe2+) sequestration, exhibiting iron-responsive fluorescence quenching with remarkable selectivity and sensitivity."
Jun Characterization of a Next-Generation Iron Oxide Coupling Medium for Transcranial Magnetic Resonance-Guided Focused Ultrasound. (Ultrasound in medicine & biology, 2026, PMID 41794603): "...synthesized with optimized Fe3+ to Fe2+ molar ratios for improved magnetic properties..."
May Inducing ferroptosis and reversing immune evasion for the suppression of melanoma lung metastasis via neferine-loaded controlled-release system. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41763265): "enabling sustained release of Nef and Fe3+, providing stable energy for ferroptosis and suppressing PD-L1 upregulation, thus enhancing T cell-mediated tumor immune surveillance and killing."
Jun A fluorescence spectrometry method for vitamin B6 determination based on its coordination reaction with Fe3. (Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 2026, PMID 41724081): "Vitamin B6 interacts with Fe3+, forming a coordination complex, increased the fluorescence signal of the reaction system."