Nonclassical odd-even alternation in mixed-chain diacylethanolamines: Implications of polymorphism

Abstract

N,O-Diacylethanolamines (DAEs), derived by the O-acylation of bioactive N-acylethanolamines (NAEs), are most likely present in biological membranes. In the present study, a homologous series of mixed chain DAEs with an N-palmitoyl chain and varying O-acyl chains (n = 6-16) have been synthesized and characterized. Differential scanning calorimetry (DSC) studies revealed a nonclassical type of odd-even alternation in the enthalpy and entropy of melting, with the odd-even effect becoming more prominent with increase in the O-acyl chain length. This was rationalized by analyzing the 3-dimensional structures of several DAEs. In most cases, two types of packing polymorphs (α and β) were observed; while the α polymorph is characterized by a mixed type of chain packing, in the β polymorph the chain packing is symmetric. Analysis of the crystal structures revealed that the odd-even effect is manifested through differences in the packing of acyl chains, with the packing being closer when both chains are even. A possible role of polymorphism in the odd-even effect has also been considered, and it was suggested that the nonclassical behavior observed in the alternation could be attributed to the presence of different fractions of the α and β forms in the bulk mixture. Similar nonclassical odd-even effects and polymorphism may exist in other mixed chain systems, which adopt an "L" shape. © 2012 American Chemical Society.