Interaction of 5-fluorouracil anticancer drug with nucleobases: insight from DFT, TD-DFT, and AIM calculations

In this study, the interaction of 5-fluorouracil (5FU) drug with adenine (A), guanine(G), cytosine(C), uracil (U), and thymine (T) nucleobases of DNA and RNA are surveyed at the omega B97XD/LANL2DZ, M06-2X/6-31G (d, p), MPW1PWQ1/6-31G(d, p), PBEPBE/6-31(d, p) and omega B97XD/6-31G(d, p) levels of density functional theory (DFT). The considered complexes of 5FU drug with nucleobases are optimized at the above level of theories. Max Force and RMS of optimization criteria are 0.00035 (Ha), and 0.0003 respectively. From optimized structures, the adsorption energy, thermodynamic parameters in gas and solvent media, quantum theory atom in molecule (QTAIM), electron localized function (ELF), and reduced density gradient (RDG) are calculated at omega B97XD/LANL2DZ and M06-2X/6-31G (d, p) level of DFT theory. The QTAIM, ELF, and RDG results confirm that the nature of bonding between 5FU drug with A, C, G, U, and T nucleobases is electrostatic or hydrogen bond type. The adsorption and thermodynamic energy results demonstrate that the interaction of the 5FU drug with C and G nucleobases is stronger than other nucleobases. The results of this study can be suggested the mechanism of interaction of the 5FU drug with nucleobases of DNA and RNA. Communicated by Ramaswamy H. Sarma

Automated summary

In this study, the interaction between the 5-fluorouracil (5FU) drug and the nucleobases of DNA and RNA (A, G, C, U, and T) was investigated using density functional theory (DFT). The optimized complexes at different levels of DFT theory were analyzed for adsorption energy, thermodynamic parameters, and molecular properties. The results suggest that the bonding between the 5FU drug and the nucleobases is mainly electrostatic or hydrogen bond type, and the interactions with C and G nucleobases are stronger than with other nucleobases. This study provides insights into the mechanism of interaction between the 5FU drug and nucleobases of DNA and RNA.