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

High Resolution Image Download MS PowerPoint Slide The targeted drug delivery systems (TDDS) minimize the adverse side effects of traditional drug delivery methods on healthy tissues. In the current study, the C 4 N 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 C 4 N 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@C 4 N as compared to TG@C 4 N. 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 C 4 N surface and APAP/TG drugs is quantified through EDD and NBO analysis. The greater decrease in the energy gap (E HOMO–LUMO ) of the C 4 N 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 C 4 N 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 C 4 N as a potential drug delivery carrier with high prospects for controlled release at the target site.