Jeff Jones

 

Address
 

Fulmer 455
Pullman, WA 99164-4630

(509) 335-5983
email: jpj@wsu.edu
Jones Group Research Page
 

Education
  • PhD Medicinal Chemistry, 1987
    University of Washington, Seattle, WA
  • BS Medicinal Chemistry, 1982
    University of Michigan, Ann Arbor, MI
 

Research

Professor Jones received his PhD in 1987 from the University of Washington, where he worked with Professor William Trager in the Department of Medicinal Chemistry. After postdoctoral work with Professor Trager and with Professor W. W. Cleland at the University of Wisconsin, he joined the Faculty of the Department of Pharmacology and Physiology at the University of Rochester. He was promoted to Associate Professor in 1996. He joined the WSU Department of Chemistry in August, 1998. We have two major projects in my laboratory. One is to develop benign synthetic pathways for the oxidation of hydrocarbons. Our second project is to predict the metabolic disposition of drugs and environmental contaminants in humans. Towards these goals, we use a combination of experimental and computational methods. Experimental methods include site-directed mutagenesis, crystallography, and kinetics. Our theoretical methods include 3-dimensional quantitative structure-activity relationships, quantum-chemical methods and molecular dynamics. A major component of either project is to understand in detail the mechanisms of enzyme mediated reactions. To this end, we make extensive use of linear free energy relationships and kinetic isotope effects. The publications listed below provide a sample of problems, methods, and approaches we use in these projects. The cytochrome P450 family of enzymes mediate the oxidation of hydrocarbons to alcohols. These reactions are extremely difficult to reproduce using conventional organic synthetic methods and most oxidation reactions generate environmentally unkind waste streams. It is our goal to harness the oxidative power of the P450 enzyme family to regio- and stereo-selectively produce alcohols from hydrocarbons. We hope to build a family of new enzymes that can be used as a starting point for the design of selective catalysts for industrially important reactions. The enzymatic reactions should be environmentally friendly and have the potential of reducing the toxicity of the products. For example, 2-ethylhexanoic acid is used in large amounts in resins, baking enamels, plasticizers and stabilizers of PVC polymers. The (R)-enantiomer of this compound is a much more potent teratogen than the (S)-enantiomer. Thus, one of our goals is to develop a biosynthetic process that produces an enantiomeric excess of the (S)-enantiomer in an environmentally friendly way. With the application of combinatorial chemistry, the pharmaceutical industry has been overwhelmed with potential drugs. While in the past the rate limiting step in drug development was synthesis and new lead compound discovery, now a large number of potential drugs are available and assessment of the absorption, distribution, metabolism and elimination (ADME) has become a potentially rate limiting component of new drug development. Our studies into the mechanism and rates of cytochrome P450 mediated reactions has allowed us to develop computational methods to rapidly determine sites of metabolism of new drug candidates. These methods can be used to help in the design of compounds with better ADME characteristics. At present we have a good model for hydrogen atom abstraction and we are attempting to incorporate other reactions, such as aromatic oxidation to phenols, into the model.

 

Publications