Role of headgroup structure in the phase behaviour of N-acylethanolamine phospholipids: hydrogen-bonding ability and headgroup size

The physical properties of aqueous dispersions of N-acylphosphatidylethanolamine from natural origin with long N-acyl chain (NAPE) and headgroup modified analogues have been studied. N-Acylation of PE causes a significant increase in the gel-to-liquid crystalline lamellar phase transition temperature in contrast with saturated N-acyl(dipalmitoyl) PEs, and in addition it does not restrict the headgroup rotational mobility in gel phase. The results agree with the increase of hydration of the phosphate group compared with that in PE and suggest the formation of hydrogen bonds between amide groups. The modifications introduced modulate the headgroup size and their hydrogen bonding capability. An increasing number of methylene groups between the phosphate and amide groups does not modify the phase behaviour observed. N-methylation of the amide group, which prevents the possibility of intermolecular hydrogen bond formation, decreases the melting temperature and the cooperativity of the phase transition and does not change the phase behaviour, while the hydration at the ester carbonyl groups level is decreased. On the other hand, the addition of N-ethyl substituent to the amide group or substitution of an ester group for this group increases its tendency to form structures with inverted geometries. The behaviour of these compounds suggests that hydration forces must be more important than considerations of the lipid dynamic shape in predicting the relative stabilities of lamellar vs. non-lamellar phases for NAPEs with long saturated N-acyl chain.