Multivariate Metal–Organic Frameworks for Dialing-in the Binding and Programming the Release of Drug Molecules

We report the control of guest release profiles by dialing-in desirable interactions between guest molecules and pores in metal-organic frameworks (MOFs). The interactions can be derived by the rate constants that were quantitatively correlated with the type of functional group and its proportion in the porous structure; thus the release of guest molecules can be predicted and programmed. Specifically, three probe molecules (ibuprofen, rhodamine B, and doxorubicin) were studied in a series of robust and mesoporous MOFs with multiple functional groups [MIL-101(Fe)-(NH₂)_x, MIL-101(Fe)-(C₄H₄)_x, and MIL-101(Fe)-(C₄H₄)_x(NH₂)_1-x]. The release rate can be adjusted by 32-fold [rhodamine from MIL-101(Fe)-(NH₂)_x], and the time of release peak can be shifted by up to 12 days over a 40-day release period [doxorubicin from MIL-101(Fe)-(C₄H₄)_x(NH₂)_1-x], which was not obtained in the physical mixture of the single component MOF counterparts nor in other porous materials. The corelease of two pro-drug molecules (ibuprofen and doxorubicin) was also achieved.