Synergistic Potential of Zidovudine Drug Encapsulating in g-C3N4 Nanosheet: A Quantum Mechanical Investigation for Enhanced HIV/AIDS Therapy

In this research, two-dimensional nanocarriers are employed to deliver zidovudine (AZT) in HIV treatment by using DFT calculations. Due to their outstanding biological compatibility and least cytotoxicity, two-dimensional nanomaterials, especially graphitic carbon nitride (g-C3N4), have gained attention as nanocarriers to improve the effectiveness and delivery of drugs at targeted regions. To examine the drug off-loading potential of the g-C3N4 molecule, electronic and quantum characteristics of AZT, g-C3N4, and AZT@g-C3N4 complex in both gas and solvent phases have been investigated. In the gas phase, when the AZT drug adsorbed on the g-C3N4 nanocarrier, it showed two non-covalent interactions such as N–H and O–H bond among nanocarrier and drug during AZT@g-C3N4 complex formation. The AZT@g-C3N4 complex has adsorption energy in the gas and solvent phase having values of − 2.54 eV and − 0.21 eV respectively. FMO analysis showed that HOMO appears on AZT drug whereas LUMO is dispersed on the g-C3N4 nanocarrier, revealing that transfer of charges will occur from drug to nanocarrier. The BSSE corrected adsorption energy is determined for AZT@g-C3N4 complex in the gas phase having values of − 54.64 kcal/mol, confirming that the complex formation is exothermic and spontaneous. The electrostatic potential (ESP) diagrams confirmed the electrophilic nature of hydrogen atoms and the nucleophilic nature of nitrogen and oxygen atoms in the AZT@g-C3N4 complex. Photo-induced electron transfer (PET) study illustrates the visual representation of electronic excitation from the drug to the nanocarrier and demonstrates that the drug behaves as electron (donor) orbitals while the g-C3N4 nanocarrier exhibits hole (acceptor) orbitals. QTAIM and NCI analysis both confirm the existence of weak Vander Waals forces and H-bonding among the drug and nanocarrier in AZT@g-C3N4 complex, and these non-covalent interactions cause the successful release of AZT drug towards the targeted area. The distribution of charges on anionic (AZT@g-C3N4−1) and cationic (AZT@g-C3N4+1) complexes has also been estimated using the atomic dipole moment corrected Hirshfeld (ADCH) charge analysis, which can help to identify active regions of the complexes and trigger further chemical reactions. Electron localization function (ELF) plots clearly show the significant variations in electron density observed in g-C3N4 carriers during complex formation with AZT drug. Furthermore, the intermolecular charge transfer mechanism and electronic transition from the g-C3N4 nanocarrier to the AZT drug and from the AZT drug to the g-C3N4 carrier are also supported by the outcomes of NBO analysis. The recovery time of AZT drug is around 0.26 s in gas phase, so it is favorable for drug desorption. This theoretical work will encourage researchers to inquire about different two-dimensional nanomaterials enabling drug delivery applications.