In the last decades, free radical processes delineated an interdisciplinary field linking chemistry to biology and medicine. Free radical mechanisms became of importance as molecular basis of physiological and pathological conditions. Lipids, in particular, unsaturated fatty acids, are susceptible of free radical attack. The reactivity of the double bond toward free radicals is well known, in particular the reversible addition of radical species to this functionality determines thecis–transdouble bond isomerization. Since the prevalent geometry displayed by unsaturated fatty acids in eukaryotes iscis, the occurrence of thecis–transisomerization by free radicals corresponds to the loss of an important structural information linked to biological activity. The formation oftransisomers can have important meaning and consequences connected to radical stress. Free radical isomerization of membrane fatty acids has been the subject of research coupling the top-down approach by model studies, such as biomimetic chemistry in liposomes, with the bottom-up approach dealing with the examination of cell membrane lipidome in living systems under several physiopathological conditions. Methodologies and molecular libraries have been settled, for both liposome experiments and the examination of the radical stress in biological membranes. This chapter will give an overview of the current procedures used for liposome models and thecis–transisomerization experiments, in order to build-up a library oftransgeometrical fatty acid isomers.
