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 (Δ H t ) and entropies (Δ S t ) 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.