Iowa Superfund Basic Research Program
Semi-volatile PCBs: Sources, Exposures, Toxicities
The Synthesis Core is responsible for the synthesis, purification and characterization of individual PCB congeners and PCB metabolites required for all research projects. This includes the development of new synthetic approaches for the preparation of PCB derivatives and their characterization by x-ray crystallography. In addition, the Synthesis Core will provide the Analytical Core with analytical PCB standard mixtures that are based on individual PCB congeners (and not technical Aroclors). These mixtures will significantly contribute to the high quality of the PCB analysis needed by most research projects.
Polychlorinated biphenyls (PCBs) are hydroxylated by cytochrome P450 enzymes and can be further metabolized to PCB quinones. Further reactions of glutathione (GSH) with PCB quinones having different degrees of chlorination on the quinone ring were examined. Electron paramagnetic resonance (EPR) spectroscopy and LC-MS revealed two types of reactions yielding different products: (1) a non-enzymatic, nucleophilic displacement of chlorine on the quinone ring yielding a glutathionyl conjugated quinone; and (2) Michael addition of GSH to the quinone, a two-electron reduction, yielding a glutathionyl conjugated hydroquinone (Scheme 1). Scheme 1: Pathways for the formation of GSH conjugates from chlorinated quinones via chlorine-substitution and Michael addition reactions. |
Core Leader: Hans-Joachim Lehmler, PhD
Dr. Lehmler is an experienced synthetic organic chemist with seven years
ofexperience in the synthesis of polychlorinated biphenyls and their metabolites
using the Suzuki coupling. He is currently appointed as Research Scientist
in the UI Department of Occupational and Environmental Health. Previously,
he was Core Project Co-Leader of a similar Research Support Core of the
University of Kentucky Superfund Basic Research Program. As Core Leader
he will oversee and coordinate the chemical synthesis and the chemical characterization
of synthetic compounds.
Core Co-Leader: Larry W. Robertson, PhD, MPH
Dr. Robertson has over twenty five years of experience in the synthesis
of polychlorinated biphenyls, their metabolites and other environmental
contaminants. His expertise in the synthesis of individual PCB congeners
using the Cadogan and Ullmann coupling as well as the Sandmeyer reaction
is an especially important asset for the Synthesis Core.
Technology Transfer efforts
The Synthesis Core has a long history of supporting researchers worldwide (especially from other superfund basic research programs) by providing individual PCB congeners as well as PCB metabolites. The Synthesis Core endeavors to continue this support as part of our research translation efforts and, whenever possible, will make test compounds available to other research programs at no or reduced cost.
Contact
Please e-mail any inquiries relating to the Synthesis Core to Hans-Joachim Lehmler at hans-joachim-lehmler@uiowa.edu.