Structural Persistence Masks Commit-Point Chemical Transformation in Copper–Imidazolate Nanosheet Metal–Organic Frameworks

Metal–organic frameworks (MOFs) are often assessed for stability using end-point structural metrics, yet their exposure-relevant chemical identity at the metal center may evolve on much shorter time scales in realistic aqueous environments. Here we examine nanoscale copper–imidazolate (CuIm) MOFs transformation across three benchmark matrices representing an abiotic-to-biorelevant gradient: a freshwater-like groundwater matrix (borehole water), a marine-like high-salinity matrix (artificial seawater), and a ligand-rich, protein-free cell-culture medium (serum-free DMEM) used here as a chemically complex challenge matrix. Using ex situ time-resolved separation of particle-associated and dissolved/complexed fractions coupled with copper-centered speciation analysis, we resolve a distinct kinetic hierarchy. CuIm remains largely conserved in borehole water, exhibits gradual reorganization in artificial seawater, and undergoes rapid transformation in serum-free DMEM, with the particle-associated fraction converging to an apparent end-state spectrum by ∼4 h. Medium-dependent copper mobilization to the dissolved/complexed pool accompanies these speciation trajectories. End-point characterization further indicates that framework-like structural signatures can persist while surface chemistry is substantially altered, demonstrating a decoupling between long-range order and node/surface identity. Collectively, these findings show that CuIm follows matrix-selected transformation trajectories with pronounced early-time trajectory shifts and that stability assessments must be grounded in time-resolved chemical identity rather than end-point crystallinity alone.