Cation-pi interaction: A strategy for enhancing the performance of graphene-based drug delivery systems

Abstract

• The obtained results indicated that the G-Be-DOX and G-Li-DOX systems show good stability and are more stable than the G-DOX complex. • G-Be-DOX complex has more interatomic interactions than the other complexes. • Drug uptake on the carrier is enhanced non-covalent interactions. To enhance the therapeutic properties of doxorubicin (DOX), a series of novel drug delivery systems (DDS) based on the cation-π complex is designed. The effect of Li, Na, K, Be, and Mg cations on the uptake of doxorubicin on the graphene (G) nanosheet has been investigated using density functional theory (DFT) calculations. Here, to design complexes, each of these cations is individually sandwiched between the graphene and DOX. All of the studied systems are fully optimized at the M06-2X/6-31G** level of theory. The obtained results indicated that the G-Be-DOX and G-Li-DOX systems show good stability and are more stable than the G-DOX complex. The adsorption energy in the most stable complex (G-Be-DOX) is about −391.089 kJ/mol. The atoms in molecules (AIM) and natural bond orbital analyses show that there are several interatomic interactions between the cations, graphene, and the drug. Furthermore, the reduced density gradient confirms the AIM results and indicates the G-Be-DOX complex has more interatomic interactions than the other complexes. In addition, molecular dynamics simulations are performed to evaluate the stability of the complexes under biological conditions. Then, an electric field with a strength of 5 V/nm was applied to the simulation systems to control drug release.