Project Summary (2010-2015)

The Synthesis Core directly supports the research function of the University of lowa SBRP research program (isbrp) by providing PCB exposure mixtures as well as individual PCB congeners and PCB metabolites.

Specific Aim 1 of the Core is the maintenance of PCB mixtures and the preparation/maintenance of analytical standards. The Synthesis Core serves as a repository for technical PCB mixtures (e.g., Aroclors 1242 and 1254) and a synthetic PCB mixture that approximates the average PCB profile found in Chicago air. In addition, the Synthesis Core maintains analytical standards that are developed in close collaboration with the Analytical Core from pure PCB/PCB metabolites.

Specific Aim 2 is the synthesis of PCB congeners for use with the in vitro and in vivo studies of the research of Drs. Schnoor, Robertson, and Goswami. These PCB congeners will also be available to the Analytical Core for the preparation of analytical and quality control/assurance standards.

Specific Aim 3 is the synthesis of methoxylated and hydroxylated PCB metabolites. Hydroxylated PCB metabolites will be used by Drs. Schnoor, Robertson, Goswami, and Duffel for in vitro and in vivo studies. Both the hydroxylated and methoxylated PCB derivatives will also be provided to the Analytical Core as analytical standards for the identification and quantification of (unknown) metabolites.

Specific Aim 4 encompasses the synthesis of miscellaneous compounds for the isbrp, including PCB quinones, PCB glutathione/N-acetyl cysteine conjugates, PCB immunogens and PCB sulfates. The Synthesis Core also provides diazomethane as derivatization agent as part of this Aim. All compounds are synthesized, if necessary in large (gram) quantities, with straight forward synthetic approaches that are well established at the University of lowa. Drawing on their extensive experience with the synthesis of organohalogen compounds, Synthesis Core staff is able to synthesize every compound of interest to the individual Research Projects.