N-Acylglycines (NAGs) with different acyl chains have been found in the mammalian brain and other tissues. They exhibit significant biological and pharmacological properties and appear to play important roles in communication and signaling pathways within and between cells. In view of this, a homologous series of NAGs have been synthesized and characterized in the present study. Differential scanning calorimetric (DSC) studies show that the transition enthalpies and entropies of dry as well as hydrated NAGs exhibit a linear dependence on the acyl chain length. Most of the NAGs show a minor transition below the chain-melting phase transition, suggesting the presence of polymorphism in the solid state. Structures of N-myristoylglycine (NMG) and N-palmitoylglycine (NPG) were solved in monoclinic system with C2/c and P21 space groups, respectively. Analysis of the crystal structures show that NAGs are organized in a bilayer fashion, with head-to-head (and tail-to-tail) arrangement of molecules. The acyl chains in both structures are essentially perpendicular to the bilayer plane, which is consistent with a lack of odd–even alternation in the thermodynamic properties. The bilayer is stabilized by strong hydrogen bonding interactions between −COOH groups of the molecules from opposite leaflets as well as N–H···O hydrogen bonds between the amide groups of adjacent molecules in the same leaflet and dispersion interactions among the acyl chains. Powder X-ray diffraction data show that the d-spacings for the NAGs with different acyl chains (n = 8–20) exhibit a linear dependence on the chain length, suggesting that all the NAGs investigated here adopt a similar packing arrangement in the crystal lattice. These observations are relevant for understanding the role of N-acylglycines in biological membranes.

Lipid-based, base-triggerable systems will be useful for colon specific targeted delivery of drugs and pharmaceuticals. In light of this, a catanionic surfactant system, composed of O-lauroylethanolamine hydrochloride (OLEA·HCl) and sodium dodecyl sulfate (SDS), has been designed. The aggregates formed by near equimolar mixtures of OLEA·HCl-SDS have shown lability at basic pH, indicating that the system may be useful for developing colon specific drug delivery system(s). Turbidimetric and isothermal titration calorimetric studies revealed that OLEA·HCl forms a 1:1 (mol/mol) complex with SDS. The three-dimensional structure of the equimolar OLEA-SDS complex has been solved by single-crystal X-ray diffraction. Analysis of the molecular packing and intermolecular interactions in the crystal lattice revealed a hydrogen bonding belt in the headgroup region of the complex and dispersion interactions among the acyl chains as the main factors stabilizing the complex. These observations will be useful in understanding specific interactions between lipids in more complex systems, e.g., biomembranes.

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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.

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