A f-19 and deuterium nmr-study of two novel fluorosterols and their properties in model membranes and high-density-lipoprotein

Fluorine-19 nuclear magnetic resonance at 235 MHz has been used to characterize the NMR properties of two novel fluorinated sterols, 6,6-difluorocholestanol and 7,7-difluorocholestanol, and various 3-ester derivatives. F-19-F-19 and F-19-H-1 coupling constants in chloroform are reported. H-2-NMR studies of side-chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) prove that the two unesterified fluorosterols affect model membrane dynamical properties in a manner analogous to cholesterol. In aqueous detergent the F-19 chemical shifts of both 6,6- and 7,7-difluorocholestanols are perturbed about 1 ppm upfield by esterification at the 3-position, suggesting that F-19-NMR may be a useful monitor of enzyme catalyzed sterol acylation in vitro. Finally 6,6-difluorocholestanol oleate has been incorporated into human high density lipoprotein (HDL) and its F-19 signals observed in this environment. The appearance of the spectrum, and the results of lipophilic relaxation probe experiments, indicate that the acyl sterol partitions into at least two environments, and exhibits slightly different chemical shift and homonuclear scalar coupling characteristics in each.