The hydrogen-bonded complexes of the 5-fluorouracil with the DNA purine bases: a comprehensive quantum chemical study

In this research work, various hydrogen-bonded complexes of 5-fluorouracil (FU), as a simplest organic anticancer drug, with the adenine and guanine purine bases were investigated. First, the molecular electrostatic potentials (MEP) of all monomers (FU, A, and G) are explored and their active sites for hydrogen-bonded interactions identified. Then, the selected plausible coplanar complexes were optimized and their complexation energies obtained. Our results reveal that the FU-G complexes are more stable than the FU-A ones. Also, the most stable structures of both series were recognized, which is consistent with the MEP results of monomers. Additionally, we estimated the strengths of the individual hydrogen bonds of the benchmark systems by energetic, geometric, spectroscopic, topological, and molecular orbital descriptors. The acceptable linear correlations between the complexation energies and some of the mentioned descriptors are observed. Finally, several aromatic indices (HOMA, ATI, NICS (0), and NICS (1)) were applied to evaluate the significant of π-electron delocalization (π-ED) of 5/6 membered rings. These results show that the π-ED of the benchmark systems increases with the formation or strengthening of the HB, which is in line with the resonance-assisted hydrogen bond theory.