Background: Many synthetic and natural uracil derivatives have biological activity. Furthermore,
many of these derivatives have pro- and antioxidant properties, but the mechanism of these
processes is far from being understood.
Methods: Oxygen-uptake kinetics and computational methods (CBS-QB3, M062X/MG3S and SMDM05/
MG3S) were combined to study the reaction of peroxyl radicals with five organic-soluble derivatives:
5-amino- and 5-hydroxy-1,3-dimethyluracil, 5-amino- and 5-hydroxy-1,3,6-trimethyluracil, and
5-hydroxy-1,3-dimethyl-6-phenyluracil in chlorobenzene.
Results: The studied uracil derivatives should be classified as inhibitors of medium reactivity kin =
(1-10) × 10-4 M-1 s-1. The methyl group in the 6-position of the pyrimidine ring increases the rate constant
of the reaction with peroxyl radicals by 3-4 times and the stoichiometric coefficient of inhibition.
The calculation of the reaction barrier heights at the SMD-M05/MG3S level of theory for the hydrogen
abstraction is in good agreement with experimental data.
Conclusion: 1,3-Dimethyl-5-aminouracil is transformed by the addition of a methyl group at the
6-position into a favic-like pyrimidine, while the 5-hydroxy derivative becomes a more effective antioxidant.
The bound dissociation energy (O-H or N-H) and the IP for the reactivity forecasting of uracil
derivatives were used, but it was found that this methodology did not lead to good correlation between
experimental and theoretical results. The SMD-M05/MG3S method provided the most accurate calculations
of the reaction barrier heights for hydrogen abstraction from uracil derivatives by peroxyl radical.