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Keywords:

  • Amphiphiles;
  • Crystal structure;
  • Microphase separation;
  • Sodium benzoate;
  • Potassium benzoate;
  • Food ingredient

Abstract

In the pharmaceutical industry many new active pharmaceutical ingredients (APIs) are marketed as carboxylic salts because of enhanced solubility and dissolution rates. These salts are, however, often hard to crystallize and/or exhibit a low degree of crystallinity. The reason may be found in the largely differing sizes of small inorganic cations and large organic anions in conjunction with the 1:1 stoichiometry, which makes it difficult to satisfy the coordination needs of the cations. Even rather small amphiphilic molecules like the widely used preservatives sodium benzoate (NaBz) and potassium benzoate (KBz) suffer of the same obstacle to crystallization. Both of these industrial products are marketed in semi-crystalline forms and no crystal structures were known up to now despite their industrial relevance. By applying long term annealing at 420 °C for 5 months we obtained tiny needle-like crystals of NaBz, which were nevertheless suitable for single crystal structure determination. Interestingly, the number of symmetry independent units in the crystal structure is exceptionally high (Z′ = 5), reflecting the difficulties in satisfying the coordination. Moreover, the small amphiphilic molecule undergoes a microphase separation into tubes with a hydrophilic core and a hydrophobic corona made up by the phenyl moieties. The tubes are arranged into a distorted hexagonal dense packing. Such microphases are well established with surfactants and block-copolymers, and it seems that even small amphiphilic molecules follow the same modes of crystallization. Interestingly, simply by changing the cation to KBz a competing microphase structure is realized. KBz crystallizes in a lamellar arrangement.