Research Support Core: Synthesis Core

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SUMMARY: Synthesis Core The Superfund Research Program at The University of Iowa (ISRP) supports investigations of the consequences of sources and exposures to all airborne polychlorinated biphenyls (PCBs), an important class of Superfund chemicals. ISRP biomedical and environmental research projects require a variety of study compounds ranging from technical and synthetic PCB mixtures to pure PCB congeners and their metabolites for studies of the volatilization, transport, exposure, toxicity, and remediation of these PCB congeners. A major obstacle for these studies is the large number of 209 PCB congeners plus the large number of 837 possible mono-hydroxylated (OH-PCBs), sulfated (PCB sulfates), glucuronidated (PCB glucuronides) and other PCB metabolites. Many of these PCB derivatives are not available from commercial sources or have never been synthesized before. Obtaining PCB mixtures or individual PCB congeners from commercial sources can also be expensive, especially if large quantities are needed for animal studies. Moreover, information about their synthesis is typically not available from commercial sources. To facilitate the innovative studies proposed by individual ISRP research projects, there is a critical need to make sufficient quantities of PCBs and their metabolites available for studies investigating the volatilization, transport, exposure, toxicity, and remediation of PCBs. To address this critical need, the major objective of the Synthesis Core is to provide a large variety of well-authenticated and highly-pure PCB derivatives in a timely and cost-efficient manner to ISRP and, as time and resources allow, other researchers. To attain this objective, the Synthesis Core will synthesize and maintain a broad range of PCB derivatives and employ rigorous guidelines for the authentication of these key chemicals. At the same time, the Synthesis Core will continue to develop novel synthetic strategies for the synthesis of PCB congeners and PCB metabolites as needed by ISRP researchers. The Specific Aims of the ISRP Synthesis Core are to: 1) maintain and prepare PCB mixtures and pure PCB congeners; 2) prepare hydroxylated PCB derivatives; 3) synthesize PCB sulfate metabolites; and 4) prepare miscellaneous compounds, such as: PCB hydroquinones, PCB catechols, PCB quinones, and PCB glutathione and N- acetylcysteine conjugates. The timely availability of PCB mixtures, individual OH-PCBs, PCB sulfates and other PCB metabolites will greatly enhance and, if the respective PCB metabolites are unavailable from commercial sources, enable the innovative studies proposed by ISRP Research Projects. Moreover, the use of well-authenticated test compounds across several ISRP research projects will greatly enhance the rigor and reproducibility of ISRP research.