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

• A homologous series of N-acylalanines (NAAs, n = 8–20) have been synthesized.
• The CMCs of NAAs in the protonated and ionized states differ significantly.
• Phase transitions of dry and fully hydrated NAAs were characterized by DSC.
• ΔHt, ΔSt, and Tt of NAAs exhibit odd–even alternation in dry and hydrated states.
• PXRD studies suggest that the NAAs most likely form tilted bilayer structures.

N-Acyl conjugates of amino acids, found in mammalian brain and other tissues, act as agonists and antagonists to receptors. In the present study, we synthesized and investigated the self-assembly, thermotropic phase transitions, and supramolecular organization of a homologous series of N-acyl-l-alanines (NAAs) containing saturated acyl chains (n = 8–20). The critical micellar concentrations (CMCs) of NAAs with shorter chains (n = 8–15) were determined by fluorescence spectroscopy, monitoring changes in the spectral characteristics of 8-anilinonapthalene-1-sulfonate. Differential scanning calorimetric (DSC) studies yielded the transition temperatures (Tt), enthalpies (ΔHt), and entropies (ΔSt) for the NAAs under dry and fully hydrated states. For longer chain length NAAs, under both dry and hydrated conditions, both ΔHt and ΔSt exhibit linear dependence on the chain length. Linear least squares analysis yielded the incremental values, ΔHinc and ΔSinc, contributed by each CH2 unit to ΔHt and ΔSt and their end contributions, ΔHo and ΔSo. Interestingly, NAAs with odd acyl chains show higher phase transition temperatures, enthalpies and entropies as compared to NAAs with even acyl chains. Powder X-ray diffraction studies showed that the d-spacings of NAAs increase linearly with chain length with an increment of 1.905 Å/CH2, suggesting that the molecules are packed in a tilted bilayer format. The present results provide a thermodynamic basis for understanding how NAAs function in their parent tissues.

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