Molecular simulation of drug adsorption and diffusion in bio-MOFs

Abstract

As the novel drug carriers, bio-metal-organic frameworks (bio-MOFs) have attracted much attention recently. As a branch of MOFs, bio-MOFs have features of low density, large specific area, and tunable structures. Bio-MOFs can be biological compatible, thus they have great potential in drug delivery and other biomedical applications. Compared with experiment, it is generally believed that molecular simulation is an efficient way for investigating the fundamental mechanisms of drug delivery in MOFs. In this work, molecular simulation studies were carried out in three bio-MOFs (bio-MOF-1, bio-MOF-11, bio-MOF-100) and one MOF (UMCM-1) to investigate the adsorption and diffusion behaviors of ibuprofen in them. To develop a reliable force field for describing the interactions between bio-MOFs and drug molecules, Gaussian 03 software was used to study the influence of basic sets and algorithms on the calculation of atomic charges of bio-MOFs atoms. Then a combined Monte Carlo and molecular dynamics (MD) simulations were carried out. Canonical Monte Carlo (NVT-MC) and Grand-canonical Monte Carlo (GCMC) simulations were employed to calculate the adsorption of ibuprofen in bio-MOFs studied. Equilibrium molecular dynamics (MD) simulations were carried out in the canonical (NVT) ensemble to investigate the diffusion behaviors of ibuprofen. The effects of the structures of bio-MOFs, the force field, and the electric charges on the adsorption and diffusion behaviors of ibuprofen in the MOFs adopted were studied systematically. In addition, the space configurations of ibuprofen in the selected bio-MOFs were analyzed. Our results show the influence of the structures of bio-MOFs on the adsorption and diffusion properties of ibuprofen molecules is big. The entry and diffusion of guest molecules are influenced greatly by pore diameters of bio-MOFs and the loading and self-diffusion coefficients of ibuprofen are proportional to the porosity of materials. Electrostatic potential enhances the adsorption towards ibuprofen molecules. In addition, we found ibuprofen molecules were preferably adsorbed around the metal ions clusters of MOFs and different optimal configurations of ibuprofen in different materials were found. The information obtained in this work is expected to apply to other theoretical and experimental studies about bio-MOFs related systems in the future.