Efficient log P determination by automated, spatially encoded 19F NMR spectroscopy

Abstract

We report a straightforward method for direct determination of log P by slice-selective ¹⁹F NMR spectroscopy utilising a single NMR sample. Our technique uses a partitioned NMR sample of n-octanol/water containing the compound of interest, a modern NMR spectrometer equipped with ¹⁹F-observation and Z-axis pulsed-field gradient capabilities in addition to automation programs to measure solute distribution between solvent layers. The approach is validated using a range of fluorinated compounds with known experimental log P values. Details of our experimental method development and implementation processes are reported in supporting data and the benefits of using this approach for experimental log P determination are highlighted.