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

Abstract

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.