Analyzing the impact of substitution on the temperature-sensitive release of doxorubicin in an imine-based covalent organic framework using molecular dynamics AITranslate

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DOI：https://doi.org/10.1016/j.commatsci.2024.112882

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Highlights • This study analyses the stability of COFs at 37 °C and 42 °C and their impact on the binding and interaction energies with DOX. • vdW interactions contribute most to DOX-COF binding energy, while ES and HB interactions were negligible. • The COFs with small polar or non-polar substitutions were unsuitable for DOX release. • COF-HQ with bulky substitution having the highest binding energy, and placement of DOX between the COF substitution layers impeded the temperature effect to release DOX. • DOX release was observed only in COF-OMe at the higher temperature of 42 °C. Nowadays, drug release through temperature control between healthy and cancer cells is also one of the most critical topics in drug delivery. Covalent organic frameworks (COFs) with specific structural units and functional groups can be optimized for efficient smart drug delivery applications. Hence, in the present study, a detailed systematic study on the release of the anticancer drug doxorubicin (DOX) in a temperature-sensitive method from COFs with structural units of 1,3,5-tris(4-aminophenyl)benzene and terephthalaldehyde substituted with hydrogen (COF-H), ethyl (COF-Et), hydroxyl (COF-OH), methoxy (COF-OMe) and 8-hydroxyquinoline (COF-HQ), by molecular dynamics (MD) simulation method at two temperatures of 37 °C and 42 °C was performed. In addition to the stability of COF systems at 37 °C and 42 °C, the results showed that changing the temperature and substitution effectively changes the binding and interaction energies between the DOX and COFs. It was understood that van der Waals (vdW) interactions, in contrast to electrostatic (ES) interactions, have the major contribution to the binding energy ( Δ G bind ° ). Also, hydrogen bonding (HB) can be effective in binding between the DOX and COFs capable of donating and accepting HBs, such as COF-HQ and COF-OH. It was seen that COFs with completely polar substitution (COF-OH) or completely non-polar substitution (COF-Et and COF-H) were unsuitable, because the DOX establishes strong interactions with these COFs by being placed on the inner surface of the cavities of the COF backbone. Also, COF with bulky substitution, COF-HQ, has the highest Δ G bind ° = −45.9108, but it was observed, due to the gradual placement of the DOX between the COF substitution layers, increasing the temperature was not able to release the DOX. Finally, DOX release was observed among the five COF systems in COF-OMe at 42 °C ( Δ G bind ° = −21.0080 kcal/mol). But at 37 °C, due to the absorption of the DOX inside COF-OMe cavities ( Δ G bind ° = −30.9486 kcal/mol), DOX release was not observed. Graphical abstract Download : Download high-res image (188KB) Download : Download full-size image