The polar group conformation of a lysophosphatidylcholine analogue in solution: A high-resolution nuclear magnetic resonance study

Abstract

The 1H and 13C resonances of 3-lauroyl-propandiol-1-phosphorylcholine in C 2H 3O 2H and 2H 2O have been assigned. LPPC ‡ ‡ Abbreviations used: LPPC, 3-lauroyl-propandiol-1-phosphorylcholine; n.m.r., nuclear magnetic resonance; p.p.m., parts per million. is present as monomers in methanol whereas it forms small micelles in water consisting of about 65 molecules. The vicinal 1H 1H, 1H 13C and 1H 31P spin coupling constants of the polar group resonances were derived from computer simulations of the 1H, 13C and 31P high-resolution nuclear magnetic resonance spectra. From an analysis of these vicinal coupling constants rotamer populations for the CC and CO bonds of the propandiol-3-phosphorylcholine moiety of LPPC were computed using a Karplus treatment (Becker, 1969). In both solvents used there is a preferred conformation in the phosphorylcholine fragment of LPPC whereas the propandiol part is flexible, as is evident from nearly equally populated rotamers around the two CC bonds of propandiol. The motionally averaged conformation of the phosphorylcholine group is characterized by an almost exclusively synclinal conformation of the choline residue (torsion angle α 5, OCCN) and by predominantly antiperiplanar conformations about the CCOP bond (torsion angle α 1) and the POCC bond (torsion angle α 4). Within the error of our conformational analysis there is good agreement between the motionally averaged conformation in solution and the crystal structure of LPPC. The average conformation in solution is independent of the solvent used and of the state of aggregation suggesting that it is mainly determined by intramolecular forces. Electrostatic interaction between the positively charged nitrogen and the anionic phosphate oxygen is responsible for stabilizing the ± synclinal conformation of the choline group. In contrast to the preferred conformation of the phosphorylcholine group, the number of possible conformations in the propandiol group is not restricted. Since, for both torsion angles θ 1 and θ 3 the three staggered conformations are equally populated, there are essentially nine possible conformational combinations for the propandiol moiety of LPPC. Since the interconversion between these different conformations is rapid on the n.m.r. time scale the LPPC molecule must have considerable flexibility about the two CC bonds of the propandiol fragment. This result indicates that there cannot be any stringent requirements for the packing of the propandiol group or the hydrocarbon chains in LPPC micelles imposing any serious constraints on the segmental motion of that group. In this respect LPPC differs markedly from diacyl phospholipids. Under comparable experimental conditions the latter class of lipids has been reported to have preferred conformations about the two CC bonds of the glycerol (torsion angles θ 1 and θ 3, Hauser et al., 1978 a, 1980). The conformational preference in that part of the molecule is a consequence of the parallel alignment of the two hydrocarbon chains optimizing hydrophobic interactions both intra- and intermolecularly. Apparently, intermolecular chain-stacking in the LPPC micelle does not restrict the number of possible rotamers in the propandiol part of the LPPC molecule.