Targeted Drug Delivery of Anticancer Agents Using C5N2 Substrate: Insights from Density Functional Theory

Cancer has a threatening impact on human health, and it is one of the primary causes of fatalities worldwide. Different conventional treatments have been employed to treat cancer, but their non-specific nature reduces their therapeutic efficacy. This study employs a C5N2-based targeted drug carrier to study the delivery mechanism of anticancer drugs, particularly cisplatin, carmustine, and mechlorethamine, using density functional theory (DFT). The geometries of the drugs, the C5N2 substrate, and the drug@C5N2 complexes were optimized at the PBE0-D3BJ/def2SVP level of theory. Interaction energy was computed for the complexes which follow the trend, i.e., cisplatin@C5N2 (−27.60 kcal mol−1) > carmustine@C5N2 (−19.69 kcal mol−1) > mechlorethamine@C5N2 (−17.79 kcal mol−1). The non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses confirmed the presence of van der Waals forces between the carmustine@C5N2 and mechlorethamine@C5N2 complexes, while weak hydrogen bonding has also been observed between the cisplatin@C5N2 complex. Electron localization function (ELF) analysis was performed to analyze the degree of delocalization of electrons within the complexes. The electronic properties of the analytes and the C5N2 substrate confirmed the enhanced reactivity of the complexes and illustrated electron density shift between the drugs and the C5N2 sheet. Recovery time was determined to assess the biocompatibility and the desorption behavior of the drugs. Moreover, negative solvation energies and increased dipole moments in a solvent phase manifested enhanced solubility and easy circulation of the drugs in biological media. Subsequently, this study illustrates that cisplatin@C5N2, carmustine@C5N2, and mechlorethamine@C5N2 complexes can be utilized as efficient drug delivery systems.