Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
Biomolecular NMR Spectroscopy Platform, Department of Biology, Swiss Federal Institute of Technology, Hönggerbergring 64, 8093, Zürich, Switzerland.
Angew Chem Int Ed Engl. 2018 Jul 20;57(30):9528-9533. doi: 10.1002/anie.201802620. Epub 2018 May 16.
Fluorine chemistry has taken a pivotal role in chemical reaction discovery, drug development, and chemical biology. NMR spectroscopy, arguably the most important technique for the characterization of fluorinated compounds, is rife with highly inconsistent referencing of fluorine NMR chemical shifts, producing deviations larger than 1 ppm. Herein, we provide unprecedented evidence that both spectrometer design and the current unified scale system underpinning the calibration of heteronuclear NMR spectra have unintentionally led to widespread variation in the standardization of F NMR spectral data. We demonstrate that internal referencing provides the most robust, practical, and reproducible method whereby chemical shifts can be consistently measured and confirmed between institutions to less than 30 ppb deviation. Finally, we provide a comprehensive table of appropriately calibrated chemical shifts of reference compounds that will serve to calibrate F spectra correctly.
氟化学在化学反应发现、药物开发和化学生物学中起着关键作用。核磁共振波谱学可以说是氟化合物特性描述最重要的技术，但其中氟核磁共振化学位移的参照极不一致，导致偏差超过 1ppm。在此，我们提供了前所未有的证据，证明无论是光谱仪设计还是异核核磁共振光谱校准所依据的现行统一标度系统，都在无意中导致了 F 核磁共振光谱数据标准化的广泛变化。我们证明，内部参照提供了最可靠、最实用且可重复的方法，可以在机构之间始终如一地测量和确认化学位移，偏差小于 30ppb。最后，我们提供了一份经过适当校准的参考化合物化学位移的综合表格，这些数据将有助于正确校准 F 谱。
