US-Nigeria Cooperative Research: Transition States for Thiophosphoryl Transfer from Phosphinothioates and Related Compounds

Utah State University, Logan UT

Investigators

Abstract

0217688 Hengge This award supports a three-year collaborative research project between Professor Alvan Hengge, with the Department of Chemistry and Biochemistry at Utah State University, and Professor Ikenna Onyido, with the Department of Chemistry at the University of Agriculture, in Makurdi, Nigeria. They will study the reaction mechanisms of phosphonothioates. Phosphoryl group transfer from a variety of phosphorylated compounds is involved in energy transport and control mechanisms in biological systems, and is critical to genetic engineering techniques. For a complete understanding of enzymatic catalysis of phosphoryl transfer, it is necessary to know the characterization of the transition state for the reaction. The investigators will measure linear free energy relationships and heavy-atom kinetic isotope effects in order to delineate the hydrolysis mechanisms of a family of thiophosphonic esters, of the general formula compounds Me2P(S)-OAr, MePhP(S)-OAr, and Ph2P(S)-OAr. The results are expected to reveal how the hydrolytic mechanism depends upon the basicity of the leaving group, as well as the comparative behavior of a group of substrates that function as, or are structurally related to, pesticides and neurotoxins. This project is at the interface of chemistry and biology, and the results are expected to advance the current knowledge about biological phosphoryl transfer at the molecular level. It combines Professor Hengge's knowledge of enzymatic and nonenzymatic phosphoryl transfer mechanisms, and Professor Onyido's expertise in the areas of mechanistic analysis and linear free energy relationships. The Office of International Science and Engineering and the Division of Chemistry are jointly providing support for this project.