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

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 H₂O₂ 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/H₂O₂ 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/H₂O₂ was proposed: thiourea is initially attacked by H₂O₂ to produce the transient intermediates formamidinesulfenic acid and then formamidinesulfinic acid, which further react with H₂O₂ 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 H₂O₂. This is the first report on metal-independent ^•OH production from the well-known ^•OH scavenging thioureas and H₂O₂, which may have important biochemical, environmental, and medical implications for future study of thiourea compounds.