Biophysical characterization of long chain O-acyl-β-alaninols and equimolar O-myristoyl-β-alaninol/sodium dodecyl sulfate complex

O-Acyl-β-alaninols (OABAOHs) are interesting amphiphiles in view of their ability to strongly inhibit N-acylethanolamine hydrolyzing acid amidase. In the present work, we synthesized and characterized long-chain OABAOHs bearing 14–20 C atoms in the acyl chain. Differential scanning calorimetric (DSC) studies showed that OABAOHs exhibit odd-even alternation in the solid-liquid phase transition enthalpies (ΔHt) and entropies (ΔSt). However, the odd- and even- chain length series independently showed linear dependence on the chain length (n) and values for the even chain length series are slightly higher than for the odd chain length series. Such odd-even alternation was not observed upon hydration, although ΔHt and ΔSt exhibited linear dependence on the chain length. Crystal structures of O-myristoyl-β-alaninol and O-palmitoyl-β-alaninol have been solved in triclinic crystal system with P-1 space group. In both structures, hydrocarbon chains of the amphiphiles are organized in a tail-to-tail format in a tilted bilayer. Powder X-ray diffraction data revealed odd-even alternation in the d-spacings of all OABAOHs, suggesting that the odd-even alternation observed in the thermodynamic properties most likely originates from differences in the crystal packing. A number of C-H⋯O and N-H⋯Cl hydrogen bonds between OABAOH molecules from adjacent and opposite layers stabilize the overall supramolecular organization of the self-assembled bilayer system. In aqueous solution, turbidimetric and isothermal titration calorimetric studies established that O-myristoyl-β-alaninol and sodium dodecyl sulfate form an equimolar complex. Transmission electron microscopic, dynamic light scattering and DSC studies indicate that the complex forms unilamellar liposomes of ∼150–160 nm diameter, which undergo a sharp thermotropic phase transition. These results provide a thermodynamic and structural basis for further investigations on OABAOHs including biomedical applications, e.g. in developing liposomal drug-delivery systems. [Display omitted] •O-Acyl-β-alaninols (OABAOHs) inhibit N-acylethanolamine hydrolyzing acid amidase (NAAA).•Biophysical and structural studies were carried out on long-chain OABAOHs.•Phase transition enthalpy and entropy of OABAOHs exhibit odd-even alternation.•The odd-even alternation originates from differences in crystal packing.•Equimolar mixtures of OMBAOH and SDS form catanionic liposomes.