Antiradical activity of N'-(1-(2,4-dioxochroman-3-yl)ethyl)-4-hydroxybenzohydrazide-thermodynamic DFT study

In the plant world, coumarins are highly represented heterocyclic compounds. This large class of compounds have found use in the treatment of numerous diseases due to one of its the most important property, and that is a strong antioxidative activity. In this paper, the antioxidative properties of newly synthesized N'-(1-(2,4-dioxochroman-3-yl)ethyl)-4-hydroxybenzohydrazide against the six selected reactive oxygen species (ROS) were investigated. To estimate antioxidative activity, DFT calculations are performed at M06-2X/6-311++G(d,p) level of theory. All calculations are accomplished in the gas phase, and the Gaussian09 software package was utilized. Analysis of the obtained thermodynamic parameters indicate single electron transfer - proton transfer (SET-PT) as not operative mechanism of free radical scavenging. On the other hand, the operative mechanistic pathways for free radical scavenging of all investigated radical species are HAT (hydrogen atom transfer) and SPLET (sequential proton loss electron transfer). One fact is interesting to note, and that is that inactivation of investigated radical species are more favourable when –NH group participates inactivating of mentioned radicals, in regard to –OH group. The difference in ΔG_BDE values between the –NH and –OH group is around 40 kJ, and the difference in ΔG_PA values is around 15 kJ in favour of –NH group, regardless of radical that is being inactivated. The radical scavenging capacity of N'-(1-(2,4-dioxochroman-3-yl)ethyl)-4-hydroxybenzohydrazide decreases in the following order ^•OH > ^•O(CH₃)₃ > ^•OCH₃ > ^•OOH > ^•OOCH₃ > ^•OOCH₃CH₂.