BACKGROUND: Several epidemiological studies indicate that moderate consumption of red wine decreases both the incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are polyphenols present in relatively large concentrations in red wine and may play a role in this cardioprotective phenomenon. The precise mechanisms of cardioprotection remain unclear but may involve the action of these polyphenols as antioxidants, which attenuate the tissue injury that results from the production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction products by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates were detected for both quercetin and the glycoside derivative, rutin, which suggests that both the conjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants toward oxidative modification of low-density lipoproteins and ABTS radical formation than the unmodified form. CONCLUSIONS: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated derivates, which exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.