Investigating the Therapeutic Activity of C ₄ N as a Targeted Drug Delivery System for Acetaminophen and Thioguanine through DFT Simulations

The targeted drug delivery systems (TDDS) minimize the adverse side effects of traditional drug delivery methods on healthy tissues. In the current study, the C₄N nanocarrier for antipyretic and anticancer drugs acetaminophen (APAP) and thioguanine (TG), respectively, is investigated by using density functional theory (DFT) simulations. The interactions between APAP/TG drugs and the C₄N surface are analyzed by using interaction energies, NCI, QTAIM, EDD, NBO, FMO, and Dipole moment analyses at the ωB97XD/6-31G (d,p) level of theory. The adsorption energies in both gas and solvent phases, including BSSE corrections, were slightly higher for APAP@C₄N as compared to TG@C₄N. The NCI analysis revealed that non-covalent interactions, dominated by van der Waals forces, play a significant role in drug-surface interactions. QTAIM analysis provides further details of the noncovalent interactions. Charge transfer between the C₄N surface and APAP/TG drugs is quantified through EDD and NBO analysis. The greater decrease in the energy gap (E_HOMO-LUMO) of the C₄N surface from 6.47 to 5.19 eV after complexation with thioguanine indicates its higher reactivity. The release behavior of the drug will show a change in dipole moment under different pH levels. The low pH, which simulates the tumor microenvironment, favors desorption of thioguanine from the C₄N carrier. To complement DFT calculations, molecular docking, and molecular dynamics (MD) simulations are carried out to assess the binding and dynamic stability of the complexes. The study characterizes C₄N as a potential drug delivery carrier with high prospects for controlled release at the target site.