Swaroop ChakrabortyIuliia MikulskaPankti DhumalNathan LangfordSusan NehzatiRhiannon BoseleySang PhamChristian PfrangManpreet KaurEugenia Valsami-JonesKonstantin IgnatyevDhruv MenonIseult LynchDr Superb Misra2026-01-272026-01-272026-01-0110.1021/acs.est.5c144872-s2.0-105027730350https://repository.iitgn.ac.in/handle/IITG2025/3398441481768Metal–organic frameworks (MOFs) hold immense potential for applications from separations to catalysis, yet their long-term behavior across real-world environments remains unclear. Here we introduce a hierarchical exposure framework that tracks the structural and chemical transformations in the archetypal zirconium MOF UiO-66 across sequential compartments─atmospheric gases, air, aqueous media and a biological host─and resolves how prior exposures condition or prime subsequent transformations. Using synchrotron-based spectroscopy, we find that oxidative/reactive gases leave the Zr-carboxylate nodes essentially intact, whereas exposure to environmentally relevant aqueous media initiates partial shifts in local Zr coordination and introduces oxygen into the pores─with transformation extent governed by the chemistry of the environmental matrices. Strikingly, acute exposure (24 h) to the water flea Daphnia magna drives profound framework degradation and respeciation to Zr hydroxide species. Microfocus XRF maps show that Zr is highly localized in the animal’s digestive tract, and region-specific XANES confirms uniform speciation across its tissues. Our findings establish a paradigm shifting cross-compartment transformation hierarchy in which biological processes can dominate the fate of stable MOFs even when abiotic exposures appear benign. Thus, organism-level biotransformation should be performed as a necessary part of environmental safety assessments and materials design.entruemetal organic frameworks (MOFs)safe-and-sustainable by designhierarchical transformationsDaphnia magnaecotoxicologyDaphnia magna | ecotoxicology | hierarchical transformations | metal organic frameworks (MOFs) | safe-and-sustainable by designArticlehttps://doi.org/10.1021/acs.est.5c14487152058512122-213620 January 20260arArticle