Structural organization of N-acyl derivatives of egg phosphatidylethanolamine into bilayers: Polymorphic and thermotropic studies

The present paper focuses on the thermotropic and polymorphic behaviour of a series of N-acylphosphatidylethanolamines of natural origin. Headgroup and N-acyl chain modifications have been introduced, and the miscibility of the synthesized compounds with the main membrane phospholipids phosphatidylcholine and phosphatidylethanolamine has been studied. The compounds N-oleoylphosphatidylethanolamine and N-stearoylphosphatidylethanolamine of natural origin, and two different types of structural analogues have been synthesized and studied: N-oleoylphosphatidylpropanolamine with one extra methylene group between the phosphate and amino groups, and the N-alkyl derivative N-methyl-N-oleoylphosphatidylethanolamine. The N-acylation of transphosphatidylated phosphatidylethanolamine (PE) with saturated acyl chains caused a significant increase in the gel-to-liquid-crystalline phase transition temperature, determined by differential scanning calorimetric analysis, but all the N-oleoyl-containing glycerophospholipids assayed showed lower transition temperatures than their precursor aminophospholipids. The presence of a third hydrophobic chain, the possibility of intermolecular hydrogen bonding between the amide groups of N-acyl PEs and the loss of the hydrogen binding ability of aminophospholipids would account for this thermotropic behaviour. The miscibility of the N-acylphospholipids with egg phosphatidylcholine and transphosphatidylated egg yolk phosphatidylcholine has also been shown by these calorimetric studies, although non-ideal mixing of these phospholipid molecules has been revealed. P-31 NMR studies have shown that the ability of the different N-acylated analogues to adopt lamellar structures is significantly different. When the N-acylation reactions were carried out with unsaturated acyl chains, the tendency to form nonlamellar phases was dramatically increased. Analysis of the P-31 NMR spectra of mixtures of the different N-acylglycerophospholipids with the main membrane constituents phosphatidylcholine and phosphatidylethanolamine has shown that these lipid molecules are miscible, in agreement with the calorimetric data.