ABSTRACT
This study focuses on the effects of the bromine atom on the molecular structure parameters in the main tautomeric forms of 5-bromouracil (5BrU), and as well, its effect on hydration and on the Watson-Crick (WC) pairs as compared to uracil molecule. The influence of the bromine atom was studied in several environments. The hydration effect on the molecular structure and energies of the main tautomeric forms of 5BrU was analyzed by considering a variable number of water molecules in explicit form up to 30 to simulate the first and second hydration shells. The 'mutagenic' 2-hydroxy-4-oxo (U2) enol tautomer of 5BrU, but not of uracil, was absolutely favored over the keto form in clusters with more than 20 water molecules. For all calculations, B3LYP and M06-2X Methods were used. The effect of the bromine atom when it was inserted into the natural and reverse WC pairs uridine-adenosine was also determined, and counterpoise (CP) corrected interaction energies were calculated. The effect of the bromine atom was analyzed in several DNA:RNA hybrid microhelices. Different backbone and helical parameters were calculated and compared. The bromine atom destabilizes its base pair, with a remarkable increase in the rise parameter (Dz) corresponding to the microhelix, and to a slight increase in the diameter (d). Molecular docking calculations were also carried out with 5BrU for targeted proteins associated with diabetes, hepatocellular carcinoma and breast and lung cancers. The molecular docking analysis confirms that the 5BrU molecule may play an important role as a promising inhibitor against breast cancer.Communicated by Ramaswamy H. Sarma.
