Radical scavenging mechanism of aryl carbamate: a computational case study using 3-morpholinopropyl phenyl carbamate

Abstract

A systematic computational mechanistic and kinetics investigation has been performed on the antioxidant activity of phenyl carbamate, namely 3-morpholinopropyl phenyl carbamate (3-MPPC), against HO^• and HOO^• radicals. The standard density functional theory (DFT) method (M062X) is used for electronic structure calculation, and conventional transition state theory and Marcus theory are used for H-transfer and electron transfer kinetics, respectively. Four types of possible reaction mechanisms, such as hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer followed by proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) have been considered here for investigation. 3-MPPC showed excellent HO^• radical scavenging activity in the gas phase (k_overall = 1.58 × 10¹¹ M⁻¹ s⁻¹), water (k_overall = 3.0 × 10⁹ M⁻¹ s⁻¹) and pentyl ethanoate solvents (k_overall = 3.8 × 10⁹ M⁻¹ s⁻¹). In the case of HOO^• radical scavenging activity, endothermic reactions with quite high activation energy are observed irrespective of the type of mechanisms. It was found that HAT is the most possible mechanism as it contributes approximately 97% and 93% to the overall rate (k_overall) in the gas phase and the lipid medium, respectively. The RAF mechanism has a minor contribution to the scavenging of HO^• radical in all the studied environments. In contrast, the SET mechanism is favorable in aqueous solution. The detailed theoretical studies will be helpful for better understanding the antioxidant activities of carbamate compounds and for further designing new potential antioxidants.