Fluorine-19 NMR Chemical Shift Probes Molecular Binding to Lipid Membranes

The binding of amphiphilic molecules to lipid bilayers is followed by ^(19)F NMR using chemical shift and line shape differences between the solution and membrane-tethered states of −CF_3 and −CHF_2 groups. A chemical shift separation of 1.6 ppm combined with a high natural abundance and high sensitivity of ^(19)F nuclei offers an advantage of using ^(19)F NMR spectroscopy as an efficient tool for rapid time-resolved screening of pharmaceuticals for membrane binding. We illustrate the approach with molecules containing both fluorinated tails and an acrylate moiety, resolving the signals of molecules in solution from those bound to synthetic imyristoylphosphatidylcholine bilayers both with and without magic angle sample spinning. The potential in vitro and in vivo biomedical applications are outlined. The presented method is applicable with the conventional NMR equipment, magnetic fields of several Tesla, stationary samples, and natural abundance isotopes.