Mechanisms of curcumin adsorption in metal-substituted MOF-74 frameworks using DFT and MD simulations

This study integrates Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations to elucidate the adsorption mechanisms and diffusion dynamics of curcumin within a series of M-MOF-74 frameworks (M = Mg, Zn, Ni, Mn, Co). DFT calculations reveal that the 4-hydroxy-3-methoxyphenyl moiety of curcumin serves as the principal electron donor (HOMO), while the heptadienone chain acts as the electron acceptor (LUMO). Electrostatic potential (ESP) mapping and reduced density gradient (RDG) analyses further identify the key noncovalent interaction sites that govern host-guest binding. Validated MD simulations demonstrate that the metal node identity profoundly influences adsorption capacity, kinetics, and binding energetics. Among the investigated systems, Co-MOF-74 exhibits the most rapid adsorption kinetics, whereas Mn-MOF-74 achieves the highest saturation capacity (59 curcumin molecules). Thermodynamic analysis establishes the binding affinity order of Mg > Mn > Co > Ni > Zn, consistent with the observed adsorption performance. Mean square displacement (MSD) analyses indicate that Zn-MOF-74 allows the highest curcumin mobility, while Mg-MOF-74 provides the strongest confinement effect. Further DFT + U calculations dissect the coordination environments at the metal open sites, linking the d-orbital electronic configurations (e.g., high-spin d⁵ for Mn²⁺ and d⁸ for Ni²⁺) to variations in Metal-O (curcumin) bond strength and covalency. Collectively, these results establish a structure-activity relationship that underscores the pivotal role of metal node selection in modulating curcumin loading, diffusion, and release behaviors in MOF-74 frameworks. This work provides mechanistic insights to guide the rational design of MOF-based drug delivery systems with tailored host-guest interactions.