title: The headgroup (a)symmetry strongly determines the aggregation behavior of single-chain phenylene-modified bolalipids and their miscibility with classical phospholipids.
abstract: In the present work, we describe the synthesis of two single-chain phenylene-modified bolalipids, namely PC-C17pPhC17-PC and PC-C17pPhC17-OH, with either symmetrical (phosphocholine) or asymmetrical (phosphocholine and hydroxyl) headgroups using a Sonogashira cross-coupling reaction as key step. The temperature-dependent aggregation behavior of both bolalipids in aqueous suspension was studied using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, small angle neutron scattering (SANS), and X-ray scattering. We show that different headgroup symmetries lead to a change in the aggregation behavior: Whereas PC-C17pPhC17-PC forms nanofibers with a diameter of 5.7 nm that transform into small ellipsoidal micelles at 23 °C, the PC-C17pPhC17-OH self-assembles into lamellae with bolalipid molecules in an antiparallel orientation up to high temperatures. Furthermore, the mixing behavior of both bolalipids with bilayer-forming phospholipids (DPPC and DSPC) was studied by means of DSC and TEM. The aim was to stabilize bilayer membranes formed of phospholipids in order to improve these mixed lipid vesicles for drug delivery purposes. We show that the symmetrical PC-C17pPhC17-PC is miscible with DPPC and DSPC; however, closed lipid vesicles are not observed, and elongated micelles and bilayer fragments are found instead. In contrast, the asymmetrical PC-C17pPhC17-OH shows no miscibility with phospholipids at all.
authors.affiliation: Institute of Pharmacy, Martin-Luther-Universitaet (MLU) Halle-Wittenberg , Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Drescher
authors.forename: Bob-Dan
authors.initials: BD
authors.lastname: Lechner
authors.forename: Vasil M
authors.initials: VM
authors.lastname: Garamus
authors.forename: László
authors.initials: L
authors.lastname: Almásy
authors.forename: Annette
authors.initials: A
authors.lastname: Meister
authors.forename: Alfred
authors.initials: A
authors.lastname: Blume
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D010767:Phosphorylcholine / Q000138:chemical synthesis* / Q000737:chemistry; D013499:Surface Properties
chemical_list: D001555:Benzene Derivatives; D008055:Lipids; D010767:Phosphorylcholine