Ethylenethiourea S-Oxidation Products: Preparation, Degradation, and Reaction with Proteins

Article abstract of DOI:10.1021/jf00057a039

Ethylenethiourea (ETU) is carcinogenic degradation product of major ethylene bis(dithiocarbamate) fungicides with biological activity attributed to poorly characterized oxidation products.The reaction of ETU with H2O2 was examined in aqueous medium at pH percent, 7, and 9 by 1H NMR spectroscopy giving five principal products: sequential formation of sulfenic, suflinic, and sulfonic acids as well as imidazoline and ethyleneurea.Maximum yields with 2 equiv of H2O2 at optimal pH were 10, 71, 5, 53, and 100percent, respectively.Oxidation proceeds mainly through the sulfinic acid to imidazoline in acidic medium and the S-oxide to ethyleneurea in basic medium. 1H NMR of urine from mice treated with ETU revealed ETU and imidazoline (no ethyleneurea or S-oxidation products).Albumin was radiolabeled in ca.17percent yield by a 10-fold excess of <14C>ETU/H2O2 oxidation products (primatily the sulfenic and sulfinic acids), and such protein modification aould be prevented by glutathione.Keywords: Ethylenethiourea; ethylenethiourea S-oxidation products; hydrogen peroxide; imidazoline; protein adducts; sulfenic acid