The focus of this research is to design artificial nucleases based on quinone methides which hydrolyse the DNA phosphate backbone under mild conditions. To determine the mechanistic details of action of quinone methides, natural products, such as mitomycin C and daunamycin, will be investigated by electrochemical studies, Nernst-Clark plots, pH rate profiles and product studies. Cyclopropyl quinone methides will be investigated by spectroscopic studies. Aziridinyl hydroquinones will be studied to obtain a structure activity relationship for fate and nucleophile selectivity of reduced aziridinyl quinones. With this award, the Synthetic Organic Program is supporting the research of Dr. Edward B. Skibo of the Department of Chemistry and Biochemistry at Arizona State University. Professor Skibo will focus his work on the study of the formation and fate of reactive species such as quinone methides.These studies will impact areas including natural product chemistry and the design of artificial DNA cleaving agents.
