Matrix-dependent transformation governs the chemical identity and biological fate of a metal–organic framework

Metal–organic frameworks (MOFs) are generally described by their pristine structures, although aqueous use and release expose them to ligands and dissolved ions that can reconstruct their coordination chemistry before biological contact. Here, we follow HKUST-1 across an environmental-to-biological exposure cascade using complementary X-ray methods. Time-resolved Cu K-edge X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure spectroscopy (EXAFS) showed rapid, matrix-specific disruption of the Cu-carboxylate paddlewheel in borehole water (BHW) and serum-free cell-culture medium (CCM). In XANES linear-combination fitting (LCF), the spectral fraction represented by pristine HKUST-1 became unresolved in BHW by 24 h and decreased to 4.1% in CCM by 4 h. The transformed solids were represented predominantly by carbonate-/hydroxide-like Cu environments in BHW and phosphate-, CuCl-, and CuO-reference-like environments in CCM. Powder X-ray diffraction, Fourier-transform infrared spectroscopy, Cu Kβ valence-to-core X-ray emission spectroscopy, carbon K-edge X-ray Raman scattering, and electron microscopy showed that transformation extended from the Cu ligand field to BTC carboxylate coordination, medium- and long-range order, and morphology. CCM generated operational <0.02 µm Cu at an initial rate of µg mL-1 h-1, compared with µg mL-1 h-1 in BHW, yet low sustained Cu mobilization in BHW did not indicate persistence of the parent framework. On a nominal material-mass basis, BHW aging increased apparent acute potency toward Daphnia magna, lowering the 48 h EC50 from 0.54 to 0.18 µg mL-1. Cryogenic X-ray fluorescence mapping and spatially resolved XANES showed further Cu re-coordination during gastrointestinal transit. Following pristine-material exposure, the HKUST-1-like contribution decreased from 10.7% in the foregut to 0.2% in the hindgut, whereas 86–98% of the Cu signal following BHW-aged-material exposure was represented by non-HKUST-1 environments throughout the gut. Framework disruption is therefore followed by matrix-selected reconstruction and biological ligand exchange. MOF performance and environmental health depend on the exposure-conditioned material, not on pristine structure or dissolved-metal concentration alone.