Nonclassical Odd–even Alternation in Mixed-Chain Diacylethanolamines: Implications of Polymorphism

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.