Forever Chemicals Never Travel Alone: How Transition Metals Reshape PFAS Toxicity and Persistence

Per- and polyfluoroalkyl substances, the notorious family of “forever chemicals” that has contaminated water supplies, soils, wildlife, and human blood on every continent, have long been studied as if they existed in a chemical vacuum. A new review published in Environmental Science and Pollution Research argues that this assumption is fundamentally incomplete. Led by Olumide Olawale Ajulo of Villanova University, an international team of researchers synthesizes evidence that transition metals—iron, copper, manganese, chromium, and vanadium among them—dramatically alter how PFAS behave in the environment and inside living organisms. The carbon–fluorine bond, one of the strongest in organic chemistry, explains why PFAS resist degradation, but the authors contend that the metals these chemicals routinely encounter in soils, sediments, groundwater, and biological tissues can change their speciation, mobility, reactivity, and toxicity in ways that PFAS chemistry alone cannot predict.

The rationale for pairing these two contaminant classes is their pervasive co-occurrence. Industrial sites, airports where aqueous film-forming foams have been discharged, mining regions, agricultural lands amended with biosolids, and urban waterways frequently carry both PFAS and elevated metal loads. When anionic PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) meet positively charged metal ions, the resulting chemistry is anything but passive. Metal cations can act as electrostatic bridges between negatively charged PFAS head groups and mineral surfaces such as goethite, an iron oxide common in soils and aquifers. Recent experimental work combined with surface complexation modeling has shown that heavy-metal ions exert direct control over PFAS adsorption on goethite in aquatic systems, meaning that the same PFAS molecule may remain immobilized in one sediment and migrate freely through another, depending entirely on the metal content of the matrix.

This metal-mediated retention has profound consequences for environmental fate. Mineralogical studies of subsurface soils and aquifers have revealed that the mineral composition of the subsurface strongly controls PFAS distribution, and laboratory work has documented substantial differences in how PFOS and PFOA sorb onto sand, clay, and iron oxide surfaces. Where metals enhance adsorption, PFAS may be sequestered for years, acting as long-term secondary sources that slowly leach into groundwater. Where metals are absent or conditions favor desorption, the chemicals travel farther and faster than standard fate models predict. The review emphasizes that water treatment infrastructure is also part of this picture: metal surfaces and metal-rich media within engineered systems can either capture PFAS or facilitate their transformation, complicating efforts to predict removal efficiency from concentration measurements alone.

Beyond simple adsorption, transition metals participate in redox reactions that can genuinely transform PFAS. Iron chemistry sits at the center of this frontier. Photochemical experiments have demonstrated that PFOA degrades under natural sunlight in the presence of ferric iron, and UV irradiation in the presence of iron-saturated montmorillonite clay achieves similar photochemical breakdown. Zero-valent iron, a material already deployed in permeable reactive barriers for other contaminants, has been shown in kinetic studies to remove PFOS from water, and computational investigations using density functional theory are now screening which transition metals bind and activate PFAS most effectively. Quantum mechanical analyses of bond activation on zero-valent iron surfaces are revealing the initial steps by which the seemingly unbreakable carbon–fluorine bonds can be cleaved. Reductive defluorination, the sequential stripping of fluorine atoms from the perfluorinated chain, has been achieved with soluble metal porphyrin systems paired with zero-valent zinc, offering a glimpse of remediation technologies that exploit exactly the metal–PFAS interactions the review describes.

The same chemistry that offers remediation promise also raises toxicological concerns, because PFAS and metals do not merely interact on mineral surfaces—they interact inside organisms. The review highlights that transition metals can modulate PFAS toxicity by altering cellular uptake, oxidative stress responses, mitochondrial function, and enzyme activity. Both contaminant classes converge on the mitochondrion, the cell’s energy factory and a major source of reactive oxygen species. Heavy metals are well established to induce mitochondrial oxidative stress and apoptosis, while PFAS independently impair mitochondrial biogenesis and dynamics, reduce oxygen consumption in human trophoblasts, and disrupt β-oxidation of fatty acids. When the two stressors co-occur, as they do in real-world exposures, their effects on the same subcellular targets may compound in ways that single-chemical toxicity testing entirely misses.

Emerging experimental evidence illustrates the stakes. In the water flea Daphnia magna, environmentally relevant combined exposure to PFOA and zinc sulfate enhanced apoptosis through binding with endogenous antioxidants, effectively overwhelming the organism’s oxidative defenses. In occupational settings, workers exposed to hexavalent chromium alongside PFAS showed effects on oxidative stress and genomic instability attributable to the mixture rather than to either agent alone. Epidemiological studies have begun to map these interactions at the population level: analyses of NHANES data have linked serum PFAS concentrations to iron status biomarkers in US adults, and recent research has implicated iron status as a mediating factor in the association between PFAS exposure and kidney function decline. Studies of children and adolescents have associated combined PFAS and heavy metal burdens with bone health outcomes, and coexposure to PFAS and blood heavy metals has been examined in metabolic dysfunction-associated steatotic liver disease.

One of the review’s most provocative arguments concerns chronic low-dose exposure. Acute toxicity from either PFAS or metals is comparatively rare at environmental concentrations, but redox-active metals can drive slow, cumulative biochemical reactions that progressively contribute to adverse health outcomes without ever triggering immediate, observable harm. Iron and copper, both redox-active, participate in Fenton-type reactions that generate hydroxyl radicals, and PFAS have been shown in subcellular studies of liver cells to generate reactive oxygen species themselves. PFOA has even been reported to induce ferroptosis, an iron-dependent form of cell death, in hepatocytes through oxidative stress and disruption of the AKT/GSK3β/β-catenin pathway. The intersection of metal-catalyzed radical generation and PFAS-driven oxidative burden creates a mechanistic framework for understanding diseases—liver steatosis, kidney decline, neurodevelopmental disorders, thyroid disruption—that epidemiology has repeatedly but inconsistently linked to PFAS exposure.

That inconsistency is precisely what the bioinorganic perspective promises to resolve. Toxicological and epidemiological studies of PFAS have produced notoriously variable results, and the review argues that metal-induced changes in PFAS bioaccumulation and biochemical reactivity may explain much of the scatter. A population drinking metal-rich groundwater may experience different internal doses and different toxicological outcomes than a population with identical measured PFAS concentrations but different metal co-exposure. PFAS binding to proteins, including serum albumin and β-lactoglobulin, may likewise be influenced by the metal milieu, altering distribution and elimination. Risk assessments built solely on PFAS concentrations, the authors conclude, systematically overlook these interactions and therefore misestimate true risk, particularly for communities living near industrial and mining sites where co-contamination is the norm rather than the exception.

The practical implications extend from monitoring to remediation to regulation. Environmental monitoring programs that measure only PFAS may misjudge bioavailability and transport; incorporating metal chemistry into fate models would sharpen predictions of where these chemicals accumulate and how long they persist. Remediation engineers are already exploiting metal–PFAS interactions, from iron-mineral amendments that strengthen PFAS removal in constructed wetlands through electron transfer mechanisms, to metal–organic frameworks that efficiently capture both short- and long-chain PFAS from water, to piezocatalytic heterojunctions designed specifically for PFAS-metal co-contaminated soils. Regulators, meanwhile, may need to consider mixture-based standards that acknowledge combined toxicity rather than chemical-by-chemical limits. As the review makes clear, forever chemicals never travel alone—and understanding their partnerships with the metals of the Earth’s crust and of our own bodies may finally explain why their effects have proven so persistent, so variable, and so hard to predict.

Subject of Research: Bioinorganic interactions between PFAS and transition metals affecting toxicity and environmental persistence

Article Title: Bioinorganic interactions between PFAS and transition metals and their effects on toxicity and environmental persistence

Article References: Ajulo, O. O., Aborode, A. T., Mudashiru, B. A., Scott, G. Y., Bakare-Abidola, T., Adenle, H., Etoniru, S. C., Olaoye, J., Obenga, E. B., Ahmad, M., Kwaku, S. D., Loubou, M. L., Blessing, U. U., Denis, M. D., Yonnison, P. A. S., & Longi, A. H. (2026). Bioinorganic interactions between PFAS and transition metals and their effects on toxicity and environmental persistence. Environmental Science and Pollution Research, 33(28), 14086-14115. https://doi.org/10.1007/s11356-026-38187-9

Image Credits: AI Generated

DOI: 10.1007/s11356-026-38187-9

Keywords: PFAS, transition metals, environmental persistence, toxicity, oxidative stress, mitochondrial dysfunction, redox chemistry, adsorption, remediation, heavy metals, groundwater contamination, risk assessment