Functional group effects on mephedrone adsorption in UiO-66-type metal-organic frameworks

Understanding how the introduction of functional groups influences the interaction between metal-organic frameworks and small organic molecules is essential for designing materials capable of mitigating the effects of psychoactive substances. In this study, a set of UiO-66-type zirconium frameworks modified with distinct linker substituents was examined to determine how these variations alter their response toward mephedrone (4-MMC). The selected functional groups introduced changes in polarity and acidity that significantly affected the behaviour of the materials in media of different composition. The framework bearing a sulfonic acid group rapidly removed nearly all detectable 4-MMC from aqueous solution, whereas derivatives containing amino-based functionalities performed more effectively under conditions resembling physiological fluids. These findings emphasise the combined influence of linker chemistry and medium composition on the uptake process. Electronic-structure calculations were used to gain deeper insight into the origin of these trends. The analysis showed that frameworks containing sulphur-based substituents form particularly stable host-guest configurations through cooperative contributions from dispersive, electrostatic, and partially covalent interactions. Aromatic stacking interactions were present but contributed less significantly than charge-related interactions. Biological evaluation confirmed that the modified frameworks exhibit minimal intrinsic toxicity and can attenuate several harmful effects produced by 4-MMC in both cell models and zebrafish larvae. Among the studied materials, the amino-functionalized derivative provided the clearest protective effect, reducing behavioural disturbances and developmental abnormalities triggered by the drug. This work demonstrates that rational modification of UiO-66 linkers offers an effective route to control the bioavailable fraction of 4-MMC, highlighting the potential of such materials for future detoxification strategies involving synthetic cathinones.