Synthesis and spectral properties of fluorescent linear alkylphosphocholines labeled with all-(E)-1,6-diphenyl-1,3,5-hexatriene

A synthetic method has been designed to produce alkylphosphatidylcholine lipid molecules with the fluorescent group all-(E)-1,6-diphenyl-1,3,5-hexatriene (DPH) incorporated to the end of a polymethylene chain of variable length. The resulting compounds may be viewed as single-chain fluorescent lipid probes terminated with a phosphocholine (PHC) polar head-group. The method was applied to the synthesis of two lipids with different alkyl chain length, PHC-C4-DPH (1) and PHC-C6-DPH (2), as well as the corresponding alcohols OH-C4-DPH (8) and OH-C6-DPH (9). The absorption and fluorescence properties of these compounds in fluid solution were very similar to those of the well-known lipid probe propionic acid-DPH (PA-DPH). In addition, it was observed that the alkylphosphocholines were easily incorporated into unilamellar lipid vesicles, in which the DPH group would be positioned most likely near the centre of the bilayer. In these conditions, 1 shows a fluorescence quantum yield of 0.4 ± 0.1 and a relatively simple decay time, with τav close to 5.0 ns. Fluorescence polarization experiments also indicate that the reorientational motions of the DPH group of phosphocholine 1 are sensitive to the fluidity changes that accompany the main thermal phase transition of the bilayer. As a result, both compounds may be of utility as novel fluorescent lipid probes, characterized by a biomimetic zwitterionic polar head-group.