a theoretical study of the separation of enantiomers of the drug modafinil by nanotubes: molecular docking simulations and density functional theory

The separation of drug enantiomers is crucial in the pharmaceutical industry, as each enantiomer can exhibit different biological activities. modafinil is a racemic drug, with the r enantiomer being primarily responsible for its pharmacological effects. the main objective of this study was to identify a suitable carbon nanotube (cnt) structure to effectively separate the enantiomers of modafinil. molecular docking simulations were performed to investigate the binding of modafinil enantiomers with various chiral cnts (7,6), (8,7), (9,8), and (10,9) with lengths ranging from 11 to 15 angstroms. molecular docking simulations showed that the cnt (8,7) with a length of 15 angstroms could effectively separate the s and r enantiomers of modafinil. the r enantiomer was adsorbed on the surface of the cnt, with a binding energy of -3.49 kcal/mol, while the s enantiomer was located inside the nanotube, with a binding energy of -4.34 kcal/mol. density functional theory (dft) calculations at the b3lyp/6-31g level were then employed to optimize the structures and investigate the interactions of the drug enantiomers with the selected cnt. density functional theory (dft) calculations revealed that the r enantiomer had a higher binding energy compared to the s enantiomer, indicating better stability upon adsorption on the cnt surface. further analysis of electronic properties, including frontier orbital energies, reactivity descriptors, mulliken atomic charges, dipole moments, and molecular electrostatic potentials, provided insights into the differences in the behavior and interactions of the two modafinil enantiomers with the cnt. in conclusion, this study demonstrates that the chiral carbon nanotube (8,7) with a length of 15 angstroms can effectively separate the s and r enantiomers of the drug modafinil, with the r enantiomer being the preferred form for adsorption and separation.