Chlorination and nitration of soy isoflavones

Diets enriched in soy foods containing a high concentration of isoflavonoid s are associated with a decrease in the incidence of several chronic inflam matory diseases. Studies with experimental models of diseases, such as athe rosclerosis, suggest that these effects can be ascribed to the biological p roperties of the isoflavones. Since the isoflavones and tyrosine have struc tural similarities and modifications to tyrosine by inflammatory oxidants s uch as hypochlorous acid (HOCl) and peroxynitrite (ONOO-) have been recentl y recognized, we hypothesized that the isoflavones also react with HOCl and ONOO-. Using an in vitro approach, we demonstrate in the present study tha t the isoflavones genistein, daidzein, and biochanin-A can be chlorinated a nd nitrated by these oxidants. These reactions were investigated using high performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. In the reaction with HOCl, both mono- and dichlorinated derivati ves of genistein and biochanin-A are formed, whereas with daidzein only a m onochlorinated derivative was detected. The reaction between genistein or d aidzein and ONOO- yielded a mononitrated product. However, no nitrated prod uct was detected with biochanin-A. Furthermore, the reaction between genist ein and sodium nitrite and HOCl yielded a chloronitrogenistein derivative, as well as a dichloronitrogenistein derivative. These results indicate that the ability of the isoflavones to react with these oxidant species depends on their structure and suggest that they could be formed under conditions where these reactive species are generated under pathological conditions. ( C) 1999 Academic Press.