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Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts

  • Thomas Martin , Paul Niemietz , Dominik Greim , Philipp Ectors , Jürgen Senker EMAIL logo , Dirk Zahn EMAIL logo und Josef Breu EMAIL logo
Veröffentlicht/Copyright: 17. August 2016
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Zeitschrift für Kristallographie - Crystalline Materials
Aus der Zeitschrift Zeitschrift für Kristallographie - Crystalline Materials Band 232 Heft 1-3

Abstract

The amphiphilic nature of benzoic acid, benzoates and benzamide causes an unexpected rich polymorphism. Featuring rather rigid and small molecular structures these compounds are ideal model systems for gaining a more fundamental understanding of molecular polymorphism by systematic and concerted investigations. The hydrophilic head allows for hydrogen bonding while the phenyl moiety gives rise to various π-stacking modes. Variations of hydrogen bonding versus π-stacking modes give rise to four polymorphs of benzamide. The central synthon in all phases is a dimer where hydrophilic units form double hydrogen bonds. As suggested by MD simulations of the nucleation process, variations of the crystallization conditions trigger whether the first self-assembly occurs via the hydrophilic head or the hydrophophic tail groups. Based on NMR crystallographic investigations for the co-crystallization of benzamide with benzoic acid, we observed yet another variation of the balance of the two dominating intermolecular interactions leading to the formation of a 1:1 co-crystal. The average crystal structure resembles the packing motive of pure benzoic acid with alternating ribbons of homogenous benzamide and benzoic acid dimers. For alkali-benzoate salts a coordination dilemma arises that is of general importance for many active pharmaceutical ingredients (APIs). A 1:1 stoichiometry requires condensation of coordination polyhedra of small inorganic cations which in turn causes steric stress that varies with the relative volumes of cation and anion. Interestingly, one way of resolving the dilemma is microphase separation which is directly related to the amphiphilic character of benzoate.

Keywords: amphiphilic molecules; benzamide; benzoate; benzoic acid; co-crystal; crystal structure; polymorphism

Acknowledgments

This work was financially supported by the Deutsche Forschungsgemeinschaft (SPP1415).

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Supplemental Material:

The online version of this article (DOI: 10.1515/zkri-2016-1977) offers supplementary material, available to authorized users.

Received: 2016-6-10
Accepted: 2016-8-2
Published Online: 2016-8-17
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Graphical Synopsis
  3. Editorial
  4. Synthesis and characterization of metastable transition metal oxides and oxide nitrides
  5. Control of organic polymorph formation: crystallization pathways in acoustically levitated droplets
  6. Thermal annealing of natural, radiation-damaged pyrochlore
  7. The formation of CdS quantum dots and Au nanoparticles
  8. Crystalline chalcogenido metalates – synthetic approaches for materials synthesis and transformation
  9. Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts
  10. A density-functional theory approach to the existence and stability of molybdenum and tungsten sesquioxide polymorphs
  11. The ZIF system zinc(II) 4,5-dichoroimidazolate: theoretical and experimental investigations of the polymorphism and crystallization mechanisms
  12. Element allotropes and polyanion compounds of pnicogenes and chalcogenes: stability, mechanisms of formation, controlled synthesis and characterization
  13. Structure and ion dynamics of mechanosynthesized oxides and fluorides
  14. Scaled-up solvothermal synthesis of nanosized metastable indium oxyhydroxide (InOOH) and corundum-type rhombohedral indium oxide (rh-In2O3)
  15. Development and application of novel NMR methodologies for the in situ characterization of crystallization processes of metastable crystalline materials
  16. Phase formation and stability in TiOx and ZrOx thin films: Extremely sub-stoichiometric functional oxides for electrical and TCO applications
  17. Investigations on the growth of bismuth oxido clusters and the nucleation to give metastable bismuth oxide modifications
  18. Divalent metal phosphonates – new aspects for syntheses, in situ characterization and structure solution
  19. Type-I silicon clathrates containing lithium
  20. Experimental and theoretical investigation of the chromium–vanadium–antimony system
  21. Synthesis and crystal structure of three new bismuth(III) arylsulfonatocarboxylates
  22. Snapshots of calcium carbonate formation – a step by step analysis
https://doi.org/10.1515/zkri-2016-1977
Schlagwörter für diesen Artikel
amphiphilic molecules; benzamide; benzoate; benzoic acid; co-crystal; crystal structure; polymorphism

Artikel in diesem Heft

  1. Frontmatter
  2. Graphical Synopsis
  3. Editorial
  4. Synthesis and characterization of metastable transition metal oxides and oxide nitrides
  5. Control of organic polymorph formation: crystallization pathways in acoustically levitated droplets
  6. Thermal annealing of natural, radiation-damaged pyrochlore
  7. The formation of CdS quantum dots and Au nanoparticles
  8. Crystalline chalcogenido metalates – synthetic approaches for materials synthesis and transformation
  9. Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts
  10. A density-functional theory approach to the existence and stability of molybdenum and tungsten sesquioxide polymorphs
  11. The ZIF system zinc(II) 4,5-dichoroimidazolate: theoretical and experimental investigations of the polymorphism and crystallization mechanisms
  12. Element allotropes and polyanion compounds of pnicogenes and chalcogenes: stability, mechanisms of formation, controlled synthesis and characterization
  13. Structure and ion dynamics of mechanosynthesized oxides and fluorides
  14. Scaled-up solvothermal synthesis of nanosized metastable indium oxyhydroxide (InOOH) and corundum-type rhombohedral indium oxide (rh-In2O3)
  15. Development and application of novel NMR methodologies for the in situ characterization of crystallization processes of metastable crystalline materials
  16. Phase formation and stability in TiOx and ZrOx thin films: Extremely sub-stoichiometric functional oxides for electrical and TCO applications
  17. Investigations on the growth of bismuth oxido clusters and the nucleation to give metastable bismuth oxide modifications
  18. Divalent metal phosphonates – new aspects for syntheses, in situ characterization and structure solution
  19. Type-I silicon clathrates containing lithium
  20. Experimental and theoretical investigation of the chromium–vanadium–antimony system
  21. Synthesis and crystal structure of three new bismuth(III) arylsulfonatocarboxylates
  22. Snapshots of calcium carbonate formation – a step by step analysis
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