Integrated Experimental and Computational Insights into the Systematic Synthesis of Cyclodextrin-based MOF

Edible cyclodextrin-based metal organic frameworks (CD-MOFs) represent a sustainable platform for green synthesis. Yet, their reproducible synthesis remains a challenge for the MOF community. In this work, we explored the reproducibility of CD-MOF synthesis and resulting structural variations through five independent sample sets, each repeated three times via a controlled methanol vapor diffusion method. Increasing reaction temperature from 25 to 50 °C enhanced the thermodynamical favorability of γ-CD-MOF crystallization, as confirmed by Density Functional Theory (DFT) calculations. After identifying the optimized synthesis conditions that produced uniform cubic crystals with a high yield (83%), the resulting γ-CD-MOFs were tested for curcumin adsorption. The maximum loading capacity of curcumin reached 24.6%, with an equilibrium uptake of 1.5 mg/g at low concentrations, consistent with Langmuir monolayer adsorption. DFT calculations and molecular simulations revealed that hydrogen bonding, hydrophobic interactions, and strong host–guest affinity (∼65 kcal/mol) govern the adsorption process, predicting a maximum theoretical uptake capacity of 195.6 mg curcumin/g γ-CD-MOF. These results establish reproducible synthesis parameters and demonstrate the enhanced curcumin loading and stabilization capability of γ-CD-MOFs, underscoring their potential as efficient carriers for bioactive molecules.