Hydrophobic vs hydrophilic: Ionic competition in remacemide salt structures

G.R. Lewis, G. Steele, L. McBride, A.J. Florence, A.R. Kennedy, N. Shankland, W.I.F. David, S.J. Teat

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Abstract

Remacemide[2-amino-N-(1-methyl-1,2-diphenylethyl)-acetamide] was developed as a potential antagonist for epilepsy, Parkinsonism, and Huntington's disease. This paper investigates hydrophilic and hydrophobic intermolecular interactions that occur within the series of crystal structures comprising remacemide 1 and six of its salts [2 = chloride; 3 = nitrate; 4 = acetate (C2H3O2-); 5 = hydrogenfumarate (C4H3O4-); 6 = naphthalene-2-sulfonate (napsilate, C10H7O3S-); 7 = 1-hydroxynaphthalene-2-carboxylate (xinafoate, C11H7O3-)]. The hydrophilic interactions are described through graph set analyses of the hydrogen bond motifs and networks. The lattice of 1 comprises unidirectional, one-dimensional chains of molecules parallel to the c-axis. In 2, the cation-anion hydrogen bonding imposes a well-defined hydrophilic stratum structure on the lattice. As the cation itself is amphiphilic, a natural consequence of this is the creation of two-dimensional stacked layers with alternating hydrophilic and hydrophobic character (lattice bilayers). This tendency to form bilayers within the lattice is also observed in structures 3-5 (polar anions) and structures 6-7 (amphiphilic anions). Relatively few well-directed intermolecular interactions are observed between aromatic rings, either in 1 or in the hydrophobic layers of 2-7. Therefore, it is concluded that it is the hydrophilic hydrogen bond interactions that dominate the crystal packing and drive the segregation into lattice bilayers in the salt crystal structures.
Original languageEnglish
Pages (from-to)427-438
Number of pages11
JournalCrystal Growth and Design
Volume5
Issue number2
DOIs
Publication statusPublished - 26 Jan 2005

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Keywords

  • Remacemide
  • antagonist
  • epilepsy
  • Parkinsonism
  • Huntington's disease
  • hydrophilic
  • hydrophobic
  • crystal structures
  • chloride
  • nitrate
  • acetate
  • hydrogenfumarate
  • naphthalene-2-sulfonate
  • 1-hydroxynaphthalene-2-carboxylate

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