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.