Self-Assembly, Supramolecular Organization, and Phase Behavior of l‑Alanine Alkyl Esters (n = 9–18) and Characterization of Equimolar l‑Alanine Lauryl Ester/Lauryl Sulfate Catanionic Complex

A homologous series of l-alanine alkyl ester hydrochlorides (AEs) bearing 9–18 C atoms in the alkyl chain have been synthesized and characterized with respect to self-assembly, supramolecular structure, and phase transitions. The CMCs of AEs bearing 11–18 C atoms were found to range between 0.1 and 10 mM. Differential scanning calorimetric (DSC) studies showed that the transition temperatures (T t), enthalpies (ΔH t) and entropies (ΔS t) of AEs in the dry state exhibit odd–even alternation, with the odd-chain-length compounds having higher T t values, but the even-chain-length homologues showing higher values of ΔH t and ΔS t. In DSC measurements on hydrated samples, carried out at pH 5.0 and pH 10.0 (where they exist in cationic and neutral forms, respectively), compounds with 13–18 C atoms in the alkyl chain showed sharp gel-to-liquid crystalline phase transitions, and odd–even alternation was not seen in the thermodynamic parameters. The molecular structure, packing properties, and intermolecular interactions of AEs with 9 and 10 C atoms in the alkyl chain were determined by single crystal X-ray diffraction, which showed that the alkyl chains are packed in a tilted interdigitated bilayer format. d-Spacings obtained from powder X-ray diffraction studies exhibited a linear dependence on the alkyl chain length, suggesting that the other AEs also adopt an interdigitated bilayer structure. Turbidimetric, fluorescence spectroscopic, and isothermal titration calorimetric (ITC) studies established that in aqueous dispersions l-alanine lauryl ester hydrochloride (ALE·HCl) and sodium dodecyl sulfate (SDS) form an equimolar complex. Transmission electron microscopic and DSC studies indicate that the complex exists as unilamellar liposomes, which exhibit a sharp phase transition at ∼39 °C. The aggregates were disrupted at high pH, suggesting that the catanionic complex would be useful to develop a base-labile drug delivery system. ITC studies indicated that ALE·HCl forms a strong complex with DNA, suggesting that the AEs may find use in DNA therapeutics as well.