Theoretical insights into the interaction of 6-Thioguanine anticancer drug with β-Cyclodextrin as a pharmaceutical Nanocarrier via density functional theory

In this study, the absorption and interaction effects of the anticancer drug 6-Thioguanine in various orientations on the β-cyclodextrin nanocarrier were theoretically investigated and optimized using Gaussian 09 software. Quantum mechanical calculations, based on Density Functional Theory with the B3LYP functional and the 6-31G* basis set, were employed to examine the influence of electronic instability, steric repulsion, and dipole-dipole interactions on the electronic properties, chemical structure, and reactivity of 6-Thioguanine in the presence of the β-cyclodextrin nanocarrier. Natural Bond Orbital analysis was conducted to evaluate dipole-dipole interactions and electronic transitions, along with calculations of the electronic properties. Density of States (DOS) diagrams illustrating the energy gaps were also generated at the same theoretical level. To further explore the molecular structure, intermolecular interactions, and dynamic behaviors, overlap parameters were calculated using the Gauge-Independent Atomic Orbital method. These calculations informed discussions on NMR and UV spectral results. Notably, the maximum wavelength shifted from 299 nm for the free 6-Thioguanine drug to 308 nm in the drug-nanocarrier complex. QTAIM analysis, ELF, and LOL evaluations demonstrated strong correlations between 6-Thioguanine and β-cyclodextrin. The findings indicate that β-cyclodextrin nanocarriers effectively facilitate the delivery of 6-Thioguanine to targeted sites, potentially minimizing associated complications. • Interaction of 6-Thioguanine with β-cyclodextrin was theoretically studied. • Electronic effects on 6-Thioguanine in β-cyclodextrin were analyzed. • Spectral results confirm drug-nanocarrier complex formation. • β-Cyclodextrin enhances 6-Thioguanine delivery to target sites.