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1H AND 13C NMR STUDY OF BRODIFACOUM STEREOCHEMISTRY AND STRUCTURE


EMSL Project ID
36393

Abstract

Brodifacoum is a lipid-soluble warfarin derivative that inhibits vitamin K epoxide reductase (VKOR) and exhibits potent anticoagulant activity. Because of its chemical stability and use in numerous popular pesticides, brodifacoum has drawn the attention of environmental regulatory agencies as a long-lived threat to non-targeted mammals and birds. As a widely produced chemical of extreme toxicity, brodifacoum is also a material of national security concern in the U.S. In evaluating the toxicological evidence and the ecological impacts of brodifacoum use, the relative amounts of brodifacoum stereoisomers in commercial products and the role of molecular structure in the binding to VKOR are pertinent questions for investigation. NMR spectroscopy has proven to be indispensible for its ability to elucidate brodifacoum's structures and conformations, particularly in hydrophobic environments, and recently we have published a complete assignment of the 1H and 13C NMR spectra of both brodifacoum diastereomers. Further analysis on EMSL 500 (4 weeks) and 750 MHz (1 week) NMR spectrometers is needed to: (1) acquire data on stereochemically pure samples (i.e., samples containing only a single brodifacoum diastereomer); and (2) determine variability in relative diastereomer concentrations of commercial brodifacoum products.

Project Details

Project type
Exploratory Research
Start Date
2010-01-15
End Date
2011-01-16
Status
Closed

Team

Principal Investigator

John Cort
Institution
Pacific Northwest National Laboratory

Team Members

Danny Mitchell
Institution
Washington State University Tri-Cities

Herman Cho
Institution
Pacific Northwest National Laboratory

Related Publications

Measurement and analysis of diastereomer ratios for forensic characterization of brodifacoum John R. Cort, Paul J. Alperin, Herman Cho 0379-0738/$ – see front matter  2011 Published by Elsevier Ireland Ltd. doi:10.1016/j.forsciint.2011.08.003