Perfluorooctyl bromide has limited membrane solubility and is located at the bilayer center. Locating small molecules in lipid bilayers through paramagnetic enhancements of NMR relaxation

There is considerable interest in the use of perfluorocarbons as oxygen carriers in clinical settings; however, little is known regarding the molecular interactions made by these apolar compounds with biological membranes or their effect on membrane structure. NMR spectroscopy was used to investigate the interaction of perfluorooctyl bromide (PFOB) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. 19 F NMR spectra demonstrate that PFOB partitions into POPC bilayers but that it saturates at a remarkably low membrane concentration of approximately 2 mol %. 19 F chemical shifts indicate that this membrane-bound PFOB experiences a local environment similar in polarity to that of hexane, suggesting that the compound resides within the hydrocarbon core of the lipid bilayer. This hydrocarbon location was refined by measuring paramagnetic enhancements of 19 F nuclear relaxation for membrane-bound PFOB produced by Gd 3+ and O 2 . The data clearly localize PFOB to the center of the membrane hydrocarbon and show how paramagnetic enhancements of nuclear relaxation produced by O 2 may be used to localize small molecules within bilayers. 2 H and 31 P NMR experiments demonstrate that PFOB produces no significant changes in either acyl chain or headgroup structure even at saturating membrane concentrations.