Radical Model of Arsenic(III) Toxicity: Theoretical and EPR Spin Trapping Studies

Arsenic is one of the most environmentally significant pollutants and a great global health concern. Although a growing body of evidence suggests that reactive oxygen species (ROS) mediate the mechanism of arsenic toxicity, the exact mechanism remains elusive. In this study, we examine the capacity of trivalent arsenic species arsenous acid (iAsIII), monomethylarsonous acid (MMAIII), and dimethylarsinous acid (DMAIII) to generate ROS through a theoretical analysis of their structures, redox properties, and their reactivities to various ROS using a density functional theory (DFT) approach at the B3LYP/6-31+G**//B3LYP/6-31G* level of theory and by employing electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Results show that the oxidized forms (AsIV) are structurally more stable compared to the reduced forms (AsII) that impart elongated As–O bonds leading to the formation of AsIII and hydroxide anion. Enthalpies of one-electron reduction...