Synthesis, characterization and thermotropic phase behavior of a homologous series of N-acyl-l-alaninols and interaction of N-myristoyl l-alaninol with dimyristoylphosphatidylcholine

Abstract

N-acylethanolamines (NAEs) and their precursors, N-acylphosphatidylethanolamines are present in the cell membranes of a variety of species and exhibit interesting biological properties. N-acyl-l-alaninols (NAAOHs) are chiral homologues of NAEs and reduced forms of N-acyl-l-alanines (NAAs) and were reported to induce apoptosis in human lymphocytes. In the present study, we have synthesized and characterized a homologous series of N-acyl-l-alaninols (n = 9 - 20). In DSC studies in the dry as well as hydrated states NAAOHs with different chain lengths showed single sharp transitions similar to N-acyl-l-alanines. Transition enthalpies (ΔHt) and entropies (ΔSt) of NAAOHs are linearly dependent on the acyl chain length in both dry and hydrated states. Powder X-ray diffraction studies showed that the d-spacings of NAAOHs exhibit linear dependence on the chain length and the incremental increase in the d values suggest that they may be packed in a tilted bilayer pattern. Studies on the interaction of N-myristoyl l-alaninol (NMAOH) with DMPC revealed that the two amphiphiles mix well up to 45 mol% of NMAOH, whereas phase separation is observed at higher contents of the alaninol. Transmission electron microscopic studies show that the NMAOH:DMPC (45:55, mol/mol) mixture forms unilamellar vesicles of about 120-150 nm in diameter.