Engineering Host-Guest Interactions in Organic Framework Materials for Drug Delivery

Metal-organic frameworks (MOF) and covalent organic frameworks (COFs) are promising nanocarriers for targeted drug delivery. Noncovalent interactions between frameworks and drugs play a fundamental role in the therapeutic uptake and release of the latter. However, the scope of framework functionalizations and deliverable drugs remains underexplored. Using a multilevel approach combining molecular docking and density functional theory, we show for a range of drugs and frameworks that experimentally reported release metrics are in good agreement with the in silico computed host-guest interaction energies. Functional groups within the framework significantly impact the strength of these host-guest interactions, while a given framework can serve as an efficient delivery agent for drugs beyond the prototypical few. Our findings identify the interaction energy as a reliable and relatively easy to compute descriptor of organic framework materials for drug delivery, able to facilitate their high-throughput screening and targeted design towards extended-release times.

Automated summary

Metal-organic frameworks (MOF) and covalent organic frameworks (COFs) have potential as nanocarriers for targeted drug delivery. Noncovalent interactions between frameworks and drugs play a crucial role in drug uptake and release. This study demonstrates a good agreement between experimentally measured release metrics and in silico computed host-guest interaction energies for a range of drugs and frameworks. The findings suggest that framework functional groups significantly impact the strength of host-guest interactions and that a given framework can be an efficient delivery agent for various drugs beyond the typical ones.