Bioinorganic interactions between PFAS and transition metals and their effects on toxicity and environmental persistence.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in water, soil, biota, and human tissues. Although their environmental persistence and toxicity are commonly attributed to the exceptional stability of the carbon-fluorine bond, increasing evidence indicates that transition metals significantly influence PFAS environmental fate, transport, and biological effects. The rationale for examining PFAS in conjunction with transition metals arises from the widespread co-occurrence of these contaminants in natural and engineered systems, where metal-mediated interactions can substantially alter PFAS behavior beyond what is predicted from PFAS chemistry alone. This article critically examines the bioinorganic interactions between PFAS and transition metals including iron, copper, manganese, chromium, and vanadium in environmental and biological matrices. These metals can influence PFAS speciation, adsorption, mobility, and reactivity through mechanisms such as surface complexation, coordination with functional head groups, and redox-mediated transformations. In environmental systems, metal-rich soils, sediments, groundwater interfaces, and water treatment infrastructures may enhance or reduce PFAS retention and transport, thereby affecting long-term persistence, environmental distribution, and bioavailability. In biological systems, transition metals may further modulate PFAS toxicity by altering cellular uptake pathways, oxidative stress responses, mitochondrial function, and enzyme activity. The interactions between PFAS and redox-active metals are particularly important under chronic low-dose exposure conditions, where biochemical reactions may progressively contribute to adverse health outcomes without immediate acute toxicity. Furthermore, metal-induced changes in PFAS bioaccumulation and biochemical reactivity may help explain inconsistencies frequently observed in toxicological and epidemiological studies. Understanding these bioinorganic mechanisms provides a more comprehensive framework for interpreting PFAS risk and highlights important limitations of risk assessments based solely on PFAS concentrations, and integrating transition metal chemistry into PFAS research is therefore essential for improving environmental monitoring, toxicological interpretation, exposure assessment, and the development of more effective remediation and regulatory strategies.