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

Marko Antonijević,Zoran Marković,Zorica Petrović,Edina Avdović,Dejan Milenković,Dušica Simijonović,Žiko Milanović,Jelena Đorović Jovanović

doi:10.3390/ecsoc-24-08372

Abstract

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 ΔGBDE values between the –NH and –OH group is around 40 kJ, and the difference in ΔGPA 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.

Highlights

Molecular oxygen is an indispensable element for the life of aerobic organisms because it enables different metabolic processes
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 structure is based on the coumarin on which is bonded to p-hydroxybenzoic acid residue by hydrazide bridge

Summary

Introduction

Molecular oxygen is an indispensable element for the life of aerobic organisms because it enables different metabolic processes This molecule is the most important electron acceptor in process of oxidative phosphorylation in the living organisms, but, by nature of its bi-radical properties, it enables a formation of partially reduced chemical species known as reactive oxygen species (ROS). Free radicals can be involved in starting a radical-chain reaction that could be potentially dangerous for the cell [1]. They are constantly forming within the cells upon exposure to drugs, pollutants, ultraviolet rays, smoke, and some endogenous metabolites of the redox and respiratory chain during the transfer of electrons [2]. Excessive exposure to free radicals can lead to the state known as oxidative stress [3]

Methods

Results

Conclusion