Progress in the synthesis of fluorinated phosphatidylcholines for biological applications

The synthesis and biophysical studies of fluorinated phospholipids have attracted a lot of interest over the past 40 years. Mono- and polyfluorinated phospholipids, containing 1-4 fluorine atoms, are designed mostly with the goal of developing new model membranes. The fluorine atoms are herein used as probes, mainly in 19F-NMR spectroscopy, to study biomolecule complexes. In this case, the spectroscopic features of the fluorine atom and the preservation of the parent lipid properties are of primary importance. On the other hand, highly fluorinated phospholipids, which contain a perfluorinated segment in alkyl chains, are mainly developed as drug-delivery devices and oxygen carriers. Here, the particular chemical characteristics of fluorine are used to form more stable and less toxic lipid vesicles/emulsions. This review will focus on describing the synthetic pathways for mono-, poly- and highly fluorinated phosphatidylcholines. We will also discuss, though not thoroughly, their properties and potential applications.