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.