Molecular and crystal structure of a self-assembling pyridinium cationic lipid

Molecular insights into cationic lipid assemblies are relatively hard to reveal due to intrinsic mobility of the structural elements, hydration of the polar head and counterion, etc. Using X-ray diffraction of 4,6-dimethyl-2-tetradecyl-1-(2-tetradecanoyloxyethyl)pyridinium hexafluorophosphate (1) single crystals we succeeded in visualizing the molecular assembly of this amphiphile, in particular its U-shape structure and the impact of various structural parameters, including the counterion. The two alkyl chains lie parallel in orthogonal planes, and that the pyridinium cationic rings appear closely to the hexafluorophosphate anions. The whole assembly has therefore nonpolar zones alternating with polar cationic–anionic channel-zones. The relevance of this molecular and crystal structure to the gene transfection ability of this cationic lipid is also discussed.