Assessing the antioxidant potential of thiamazole through the HAT, SETPT, and SPLET antiradical mechanisms of hydrogen abstraction using DFT.

CONTEXT: Regarding the importance of employing antioxidants for dealing with the wild free radicals in the human body system, we performed this work for exploring a potential antioxidant compound. The major HAT, SETPT, and SPLET antiradical mechanisms for exploring the antioxidant potential of thiamazole were assessed through the hydrogen abstraction from all hydrogen involving atomic sites of chemical structure. The hydrogen abstraction from the C-H, N-H, and S-H groups of thio and thiol tautomeric conformers of thiamazole (T1 and T2) were considered to assess the antiradical mechanisms. The evaluated results demonstrated the suitability of models for the hydrogen abstraction from the N-H and S-H groups rather than the C-H group but with a limitation of targeting S-H group in the case of supplying an enthalpic barrier of T2 formation. Additionally, the HAT mechanism was found as the best pathway of antiradical mechanism for thiamazole and the SETPT and SPLET mechanisms were placed in the next levels of preference. As a remarkable conclusion, thiamazole could be considered for working as a potential antioxidant regarding the meaningful thermochemical features of antiradical mechanism; however, the kinetic features and clinical limitations are still major concerns to be resolved before proposing for a real practical use.

METHODS: Density functional theory (DFT) calculations were performed using the B3LYP functional and the 6-311 +  + G** and 6-311G** basis sets as implemented in the Gaussian 16 software.