Defect-engineered modulation of metal–oxygen coordination environments in metal–organic frameworks for flavonoid delivery

A defect-engineering strategy was applied to construct a highly efficient flavonoid carrier based on zirconium-thiophenedicarboxylate framework (DUT-67). By utilizing 2-thiophenecarboxylic acid (2-TC) as a secondary modulator (acetic acid as a primary one), defective DUT-67 with abundant available zirconium sites was synthesized, achieving an optimized defect extent and high specific surface area (1237 m² g⁻¹). The optimized DUT-67-B demonstrated exceptional adsorption capacities of 246.1 mg g⁻¹ for quercetin (Que) and 116.3 mg g⁻¹ for kaempferol (Kae), outperforming most reported metal-organic frameworks and conventional adsorbents. The adsorptions of Que and Kae both follow Langmuir isotherm and pseudo-second-order kinetics models, and the kinetics behavior can be well described by intraparticle diffusion model. The adsorbent retains 90.2% of its initial capacity after four consecutive cycles, using cool acidic methanol as the eluent. The loaded Kae and Que molecules are selectively released in simulated gastric fluid rather than under neutral physiological conditions (normal human tissue); moreover, Kae is released more readily than Que owing to its weaker Zr–oxygen coordination interaction. Mechanistic studies combining experimental characterizations with theoretical calculations revealed that chemisorption via Zr–phenol coordination dominates the adsorption process, and acidic media disrupt this interaction, thereby triggering drug release. Additionally, Que exhibits significantly stronger affinity than Kae due to its terminal dual-phenol structure enabling bidentate coordination with two adjacent zirconium sites (binding energy nearly double that of Kae monodentate binding). This work highlights the critical role of defect-engineered open metal sites in modulating flavonoid adsorption/release, and offers a design principle for constructing high-performance drug-delivery carriers.