Covalent Organic Frameworks for Drug Delivery

Gregor J. Lauter, Alessandro Calzolari, Ganna Gryn’ova

Covalent organic frameworks (COFs) are highly ordered porous two- or three-dimensional polymers consisting of regularly connected nodes and linkers and characterised with diverse topologies, compositions, and properties.[1] Voids inside the frameworks can be constructed to the desired dimensions and can accommodate a variety of guests: photons and excitons, electrons and holes, ions and molecules, enabling their uses as catalysts, chemosensors, and nanocarriers for biologically active targets.[2] In this work we focus on capture, transport, storage, and release of drugs in/by COFs – a research avenue promising targeted delayed- release delivery of therapeutics by customisable, responsive, and biocompatible materials. We aim to develop a computational approach for predicting the encapsulation and uptake of drug molecules within the cavities of COFs, leveraging their structural characteristics. Our approach combines force field (FF)-based Molecular Dynamics, Density Functional Theory, and Grand Canonical Monte Carlo simulations. To further analyse the non-covalent interactions (NCIs) between the host COFs and the guest molecules, we are also developing dedicated NCI descriptors and structural fingerprints. Overall, these tools will allow not only the design of novel materials but also the rapid pre-assessment of their efficacy in applications related to the sequestration of small molecules.

Figure 1. Schematic workflow for the generation of NCI descriptors and structural fingerprints.

1. Côté, Benin, Ockwig, O’Keeffe, Matzger, Yaghi, Science 2005, 310, 1166.
2. Huang, Wang, Jiang, Nature Rev. Mater. 2016, 1, 16068.

 Gregor J. Lauter