A Luminescent Mg-Metal–Organic Framework for Sustained Release of 5‑Fluorouracil: Appropriate Host–Guest Interaction and Satisfied Acid–Base Resistance

It is important to achieve a moderate sustained release rate for drug delivery, so it is critical to regulate the host–guest interactions for the rational design of a carrier. In this work, a nano-sized biocompatible metal–organic framework (MOF), Mg­(H2TBAPy)­(H2O)3·C4H8O2 (TDL-Mg), was constructed by employing π-conjugated 1,3,6,8-tetrakis­(p-benzoic acid)­pyrene (H4TBAPy) as a ligand and used for 5-fluorouracil (5-FU) loading (28.2 wt %) and sustained slow release. TDL-Mg exhibits a 3D supramolecular architecture featuring a 1D rectangle channel with a size of 6.2 × 8.1 Å2 and a Brunauer–Emmett–Teller surface area of 627 m2·g–1. Channel microenvironment analysis shows that the rigid H2TBAPy2– ligand adopts special torsion to stabilize the channels and offer rich π-binding sites; the partially deprotonated carboxyls not only participate in the formation of strong hydrogen bonds but also create a mild pH buffer environment for biological applications. Suitable host–guest interactions are generated by the synergistic effect of polydirectional hydrogen bonds, multiple π-interactions, and confined channels, which allow 5-FU@TDL-Mg to release 76% of load in 72 h, a medically reasonable rate. Microcalorimetry was used to directly quantify these host–guest interactions with a moderate enthalpy of 22.3 kJ·mol–1, which provides a distinctive thermodynamic interpretation for understanding the relationship between the MOF design and the drug release rate. Additionally, the nano-sized 5-FU@TDL-Mg can be taken up by mouse breast cancer cells (4T1 cells) for imaging based on the dramatic fluorescence change during the release of 5-FU, exhibiting potential applications in biological systems.