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.

Self-assembly, supramolecular organization, and phase transitions of a homologous series of N-acyl-l-alanines (n=8–20)

“…However, this type of odd-even alteration was observed earlier with phosphatidylcholines bearing -tertiary-butyl fatty acyl chains and phosphatidylcholines containing dl-methyl anteisobranched fatty acyl chains in the hydrated state [34,35]. The enthalpy and entropy data for NAAs of even and odd acyl chain lengths could be fit well to expressions (2) and (3) [29] given below as observed previously with N-acylethanolamines, Nacyldopamines, and N-acylserotonins with even and odd acyl chain lengths, O-acylcholines with even chain lengths as well as N-,Odiacylethanolamines with matched as well as mixed acyl chains [31][32][33][36][37][38][39].…”

Synthesis, physicochemical characterization and membrane interactions of a homologous series of N-acylserotonins: Bioactive, endogenous conjugates of serotonin with fatty acids

“…The odd-even alternation seen in the transition enthalpies, transition entropies and transition temperatures of NASTs is similar to the alternation observed previously in the thermodynamic properties of a number of other amphiphilic molecules such as long-chain hydrocarbons, fatty acids, N-acylethanolamines, N-, O-diacylethanolamines with matched as well as mixed chains, and N-acyldopamines in the solid state [26,[30][31][32][33][34]. This could be explained on the basis of differences in the packing of hydrocarbon chains.…”

Same or different – that is the question: identification of crystal forms from crystal structure data

“…In all cases, the PXS is above 0.965. For the third pair, DAWFUE-DAWFUE01, 76 the PXS is close to the limit usually chosen for differentiating structures (0.972). Simulated PXRDs for the pairs are plotted in Fig.…”