title: (1)H and (13)C NMR chemical shift assignments and conformational analysis for the two diastereomers of the vitamin K epoxide reductase inhibitor brodifacoum.
abstract: Proton and (13)C NMR chemical shifts and (1)H-(1)H scalar couplings for the two diastereomers of the potent vitamin K epoxide reductase (VKOR) inhibitor brodifacoum have been determined at 293 K from acetone solutions containing both diastereomers. To facilitate difficult assignments, homo- and heteronuclear correlation spectra were acquired at 750 and 900 MHz over 268-303 K temperature range. Conformations of both diastereomers inferred from the scalar couplings and 1-D NOE measurements reveal that one diastereomer (SS/RR) adopts a strained geometry in the cyclohexene ring system of the tetralin group. The NMR spectra also show evidence of line broadening due to conformational exchange at room temperature for the SR/RS diastereomer. These assignments and conformational analyses may be useful in studies of biomolecular interactions of brodifacoum with target proteins such as VKOR and in source determination of brodifacoum.
authors: Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors: John R
authors: JR
authors: Cort
authors: Herman
authors: H
authors: Cho
mesh_terms: D015110:4-Hydroxycoumarins / Q000032:analysis*; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D011522:Protons; D012015:Reference Standards; D013237:Stereoisomerism; D064417:Vitamin K Epoxide Reductases
chemical_list: D015110:4-Hydroxycoumarins; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; D011522:Protons; C013418:bromfenacoum; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases