Heteroatom (B, N, P, and S)-Doped Cyclodextrin as a Hydroxyurea (HU) Drug Nanocarrier: A Computational Approach

[Image: see text] Theoretical examination of hydroxyurea adsorption capabilities toward the cyclodextrin surface for proper drug delivery systems was carried out utilizing DFT simulations. The study aims to assess the efficacy of doped cyclodextrin (doped with boron, nitrogen, phosphorus, and sulfur atoms) in increasing its stability and efficiency in intermolecular interactions, hence facilitating optimal drug delivery. The adsorption energies were found to follow a decreasing order of B@ACD-HU>N@ACD-HU>P@ACD-HU>S@ACD-HU with energies of −0.046, −0.0326, −0.015, and 0.944 kcal/mol, respectively. The S@ACD-HU complex, unlike previous systems, had a physical adsorption energy. The N@ACD-HU and B@ACD-HU complexes had the shortest bond lengths of 1.42 Å (N122-C15) and 1.54 Å (B126-C15), respectively. The HOMO and LUMO values were also high in identical systems, −6.367 and −2.918 eV (B@ACD-HU) and −6.278 and −1.736 eV (N@ACD-HU), respectively, confirming no chemical interaction. The N@ACD-HU has the largest energy gap of 4.54 eV. For the QTAIM analysis and plots, the maximum electron density and ellipticity index were detected in B@ACD-HU, 0.600 au (H70-N129) and 0.8685 au (H70-N129), respectively, but N@ACD-HU exhibited a high Laplacian energy of 0.7524 a.u (H133-N122). The fragments’ TDOS, OPDOS, and PDOS exhibited a strong bond interaction of greater than 1, and they had different Fermi levels, with the highest value of −8.16 eV in the N@ACD-HU complex. Finally, the NCI analysis revealed that the complexes were noncovalent. According to the literature, the van der Waals form of interactions is used in the intermolecular forces of cyclodextrin cavities. The B@ACD-HU and N@ACD-HU systems were more greenish in color with no spatial interaction. These two systems have outperformed other complexes in intermolecular interactions, resulting in more efficient drug delivery. They had the highest negative adsorption energies, the shortest bond length, the highest HOMO/LUMO energies, the highest energy gap, the highest stabilization energy, the strongest bonding effect, the highest electron density, the highest ellipticity index, and a strong van der Waals interaction that binds the drug and the surface together.