Head/tail selective deuteration of phospholipids with unsaturated oleoyl or branched phytanoyl fatty acid chains

Phospholipid derivatives with unsaturated or branched fatty acid chains are fundamental to the structure and function of cellular membranes. As a result, there has been increasing interest in the availability of their deuterated forms for many neutron scattering studies, as well as nuclear magnetic resonance and other spectroscopic techniques. Here, we present detailed procedures for straightforward, large-scale synthesis of deuterated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and deuterated 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). The precursors for the synthesis of the deuterated oleic acid chains of DOPC are [D14]azelaic acid and [D17]nonanoic acid, which were obtained by complete deuteration (>98% D) of their ¹H forms by using metal catalysed hydrothermal H/D exchange reactions. The Phytanic acid chains of DPhPC were deuterated directly under similar hydrothermal conditions. The subsequent syntheses of the corresponding phospholipids, selectively deuterated at the tail or head group, are also described. These selectively deuterated lipids are suitable for contrast matching techniques in neutron studies, where one wishes to highlight or mask out the hydrophobic or hydrophilic parts of the bilayer lipid membrane models.