Molecular Mechanism for the Unprecedented Metal-Independent Hydroxyl Radical Production from Thioureas and H 2 O 2 .

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.