Structure and Thermotropic Phase Behavior of a Homologous Series of N-Acylglycines: Neuroactive and Antinociceptive Constituents of Biomembranes

Abstract

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.

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

“…In the case of N-acylglycines, the incremental increase in dspacing per additional CH 2 group in the acyl chain was obtained from PXRD studies as 2.645Å, which suggested that the acyl chains in them should be perpendicular to the plane of the bilayer [43]. Consistent with this, single-crystal X-ray diffraction studies on N-myristoylglycine and N-palmitoylglycine showed that the alltrans acyl chains in them have tilt angles of 0.03 • and 0.84 • , respectively, with respect to the bilayer normal, which are negligible when compared with the tilt angle estimated for the NAAs from PXRD measurements.…”

Interplay of noncovalent interactions in antiseptic quaternary ammonium surfactant Miramistin

“…Chloride ions and water molecules form a hydrogen-bonded anionic zigzag chain core along the a crystal axis. This feature of MR is in contrast to neutral amides, including the long-chain alkyl derivatives, which are typical coformers of the N-HÁ Á ÁO C hydrogen-bonded supramolecular synthons in onedimensional chain aggregates (Ramakrishnan & Swamy, 1999;Reddy et al, 2014;Masuda et al, 2005;Dastidar, 2008;Bastiat & Leroux, 2009). 2).…”

Differential scanning calorimetric and powder X-ray diffraction studies on a homologous series of N-acyl-L-alanine esters with matched chains (n = 9-18)

“…In previous work, we have synthesized and characterized the self assembly, supramolecular organization and thermotropic phase behavior of N -acylalanines and N -acylglycines. 7,13 While N -acylation of glycine and alanine yields anionic amphiphiles, esterification of these amino acids with long chain alcohols would give cationic amphiphiles which may find use in developing catanionic lipid based drug delivery systems. Therefore, we have also synthesized a homologous series of L-alanine alkyl esters and characterized them with respect to aggregation properties in aqueous dispersion, 3-dimensional structure as well as interaction with sodium dodecyl sulfate.…”

“…The product obtained was recrystallized from dichloromethane at −20 • C. Overall yields of different NAAEs ranged around 80-90%. The final product thus obtained was filtered and dried by vacuum desiccation, and characterized by FTIR, 1 H-NMR, 13 C-NMR and HRMS.…”

“…Representative FTIR, 1 H-NMR, 13 C-NMR and HRMS spectra of N -decanoyl-L-alanine decyl ester are given in Figures S1-S4. Corresponding spectral data for all NAAEs (n = 9-18) are given in tables S1-S4.…”