Design of a new drug delivery platform based on surface functionalization 2D covalent organic frameworks

The adsorption mechanism of doxorubicin (DOX) on pristine covalent organic frameworks (COF) and functionalized COF (F-COF) is investigated by using molecular dynamics (MD) and Metadynamics simulations. MD simulations are performed to explore the loading of DOX into the COFs. To evaluate this process, a set of descriptors, including interaction energies, radial distribution function, and square mean displacement, the number of hydrogen bonds (HB) are calculated throughout the simulation trajectories. It is determined that HB interactions are the most important factors in stability of the investigated systems. The MD results show that the drug molecules move toward the COFs and form the stable complexes. Functionalization of COF with six and three hydroxyl groups increases its interaction energy with DOX from -16.87 to -264.95 and -139.87 kJ/ mol, respectively. In this study, the free energy surface (FES) is also calculated by well-tempered metadynamics simulation technique. The PES landscapes confirm that the global minimum could be typically relevant to formation of the HB. The free energy values for the COF/DOX complexes in pristine and functionalization of COFs at their global minima are reached about -229.7, -260.46 (for six OH groups), and -243.37 (for three OH groups) kJ/mol, respectively. In addition, at the acidic condition, protonation of DOX causes that the interactions between DOXs and the COFs become weaker and drug molecules could release from the nanocarrier cavities. (c) 2021 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.