Computational analysis of B, N, and S-doped coronene as an effective drug delivery system for the anti-cancer drug hydroxyurea

This study presents the investigation of doped-Coronene as a carrier for the delivery of the anticancer drug, Hydroxyurea. The efficacy of doped-Coronene as a carrier was examined through the analysis of various physicochemical and electronic properties, using density functional theory (DFT). All the geometries including drug, carriers and their complexes were optimized using the B3LYP functional with the 6–311++G(d,p) basis set. Here two different types of doped-Coronene were investigated against the Hydroxyurea drug: BN-doped Coronene ($C_{18}{H}_{12}{B}_3{N}_3$) and BNS-doped Coronene ($C_{21}{H}_{12}\mathrm{BNS}$). Both $C_{18}{H}_{12}{B}_3{N}_3$ and $C_{21}{H}_{12}\mathrm{BNS}$ physisorbed Hydroxyurea, with adsorption energies of −82.97 kJ/mol and −80.42 kJ/mol, respectively. Frontier molecular orbitals (FMO) analysis revealed that charge was transferred from the Hydroxyurea to the carrier during the complex formation process. The analogous properties of the Hydroxyurea drug were further validated by electron localization function (ELF) and electrostatic potential (ESP) measurement. Moving further, the charge decomposition analysis (CDA) was explored to provide a more detailed understanding of charge-transfer mechanism. Non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses identified weak van der Waals forces, attractive interactions, and low electron density at bond critical points, supporting easy drug detachment at the target site. In the solvent phase, adsorption energies decreased significantly, −35.55 kJ/mol for $\mathrm{HU}@C_{18}{H}_{12}{B}_3{N}_3$ and −35.10 kJ/mol for $\mathrm{HU}@C_{21}{H}_{12}\mathrm{BNS}$. This indicates that Hydroxyurea is likely to be released more easily in a physiological environment. Global reactivity descriptors and dipole moment values yielded favorable stability and reactivity for drug delivery applications. Overall, our computational analysis suggests that doped-Coronene could be a potential candidate for the delivery of Hydroxyurea.