Molecular Mechanism for the Unprecedented Metal-Independent Hydroxyl Radical Production from Thioureas and H₂O₂

Abstract

The most well-known hydroxyl radical ( • OH)-generating system is the classic iron-mediated Fenton reaction. Thiourea has been considered as an efficient • OH scavenger and is frequently used to study the role of • OH in various biochemical and medical research studies. Here we found that the highly reactive • OH can be produced from thiourea and H 2 O 2 through a metal-independent pathway, as measured by electron spin resonance (ESR) secondary radical spin-trapping and fluorescent methods. The major reaction intermediates from thiourea/H 2 O 2 were identified as formamidinesulfenic acid and formamidinesulfinic acid, with urea and sulfate as the major final products. Taken together, the underlying molecular mechanism for the unprecedented • OH production from thiourea/H 2 O 2 was proposed: thiourea is initially attacked by H 2 O 2 to produce the transient intermediates formamidinesulfenic acid and then formamidinesulfinic acid, which further react with H 2 O 2 to produce their corresponding hydroperoxyl intermediates, which can decompose homolytically to generate • OH and the final products. Analogous • OH production and oxidative DNA damage were also observed with other thiourea derivatives and H 2 O 2 . This is the first report on metal-independent • OH production from the well-known • OH scavenging thioureas and H 2 O 2, which may have important biochemical, environmental, and medical implications for future study of thiourea compounds.