The reactions of phosphodiesters with epoxides : model studies to understanding the interaction of PAH epoxides with nucleic acids

Abstract

The reaction of polycyclic hydrocarbon epoxides with the phosphate group of DNA has been suggested as potentially important in the cancer process initiated by this class of compounds. Herein the chemical reactions of model phosphates with various classes of epoxides are investigated. With aliphatic and non-bay-region type expoxides the reaction occurred by stereospecific trans addition of phosphate on the epoxide. Various physical-chemical aspects of this reaction are investigated. With K-region type epoxides the same reaction gave exclusively phenols. The biological implications of this result are discussed. Finally, bay-region type oxides, on reaction with phosphate, gave phosphotriesters whose stabilities depend on the phosphodiester nucleophile used and on the presence and arrangement of the diol grouping next to the epoxide