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Zeitschrift für Kristallographie - Crystalline Materials

Editor-in-Chief: Pöttgen, Rainer

Ed. by Antipov, Evgeny / Boldyreva, Elena V. / Friese, Karen / Huppertz, Hubert / Jahn, Sandro / Tiekink, E. R. T.

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Volume 232, Issue 1-3

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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 / Dirk Zahn / Josef Breu
Published Online: 2016-08-17 | DOI: https://doi.org/10.1515/zkri-2016-1977

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.

This article offers supplementary material which is provided at the end of the article.

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

References

  • [1]

    J. Bernstein, Polymorphism of dyes and pigments, in Polymorph. Mol. Cryst., Oxford University Press, Oxford, p. 257, 2007.Google Scholar

  • [2]

    K. Kadish, R. Guilard, K. M. Smith, The Porphyrin Handbook: Applications of Phthalocyanines, Elsevier Science, 2012.Google Scholar

  • [3]

    J. M. Oyarzún, Pigment Processing: Physico-Chemical Principles, Vincentz Network GmbH & Co KG, 2000.Google Scholar

  • [4]

    B. Olenik, G. Thielking, Polymorphism and the organic solid state: influence on the Optimization of Agrochemicals, in Mod. Methods Crop Prot. Res., Wiley-VCH, p. 249, 2012.Google Scholar

  • [5]

    R. J. Davey, N. Blagden, G. D. Potts, R. Docherty, Polymorphism in molecular crystals: Stabilization of a metastable form by conformational mimicry. J. Am. Chem. Soc. 1997, 119, 1767.CrossrefGoogle Scholar

  • [6]

    S. R. Hall, P. V. Kolinsky, R. Jones, S. Allen, P. Gordon, B. Bothwell, D. Bloor, P. A. Norman, M. Hursthouse, A. Karaulov, J. Baldwin, M. Goodyear, D. Bishop, Polymorphism and nonlinear optical activity in organic crystals. J. Cryst. Growth 1986, 79, 745.CrossrefGoogle Scholar

  • [7]

    W. Wang, M. Aggarwal, J. Choi, T. Gebre, A. D. Shields, B. G. Penn, D. O. Frazier, Solvent effects and polymorphic transformation of organic nonlinear optical crystal L-pyroglutamic acid in solution growth processes. J. Cryst. Growth 1999, 198–199, 578.Google Scholar

  • [8]

    J. Haleblian, W. McCrone, Pharmaceutical applications of polymorphism. J. Pharm. Sci. 1969, 58, 911.CrossrefGoogle Scholar

  • [9]

    R. Hilfiker, Polymorphism: In the Pharmaceutical Industry, John Wiley & Sons, 2006.Google Scholar

  • [10]

    J. Bernstein, Polymorphism in Molecular Crystals, Oxford University Press, Oxford, 2007.Google Scholar

  • [11]

    J. D. Dunitz, J. Bernstein, Disappearing polymorphs. Acc. Chem. Res. 1995, 28, 193.CrossrefGoogle Scholar

  • [12]

    D.-K. Bučar, R. W. Lancaster, J. Bernstein, Disappearing polymorphs revisited. Angew. Chem. Int. Ed. 2015, 54, 6972.CrossrefGoogle Scholar

  • [13]

    E. Gibney, Software predicts slew of fiendish crystal structures. Nature 2015, 527, 20.CrossrefGoogle Scholar

  • [14]

    W. Ostwald, Studien über die Bildung und Umwandlung fester Körper. 1. Abhandlung: Übersättigung und Überkaltung. Z. Phys. Chem. 1897, 22, 289.Google Scholar

  • [15]

    U. Kolb, T. Gorelik, C. Kübel, M. T. Otten, D. Hubert, Towards automated diffraction tomography: part I – Data acquisition. Ultramicroscopy 2007, 107, 507.CrossrefGoogle Scholar

  • [16]

    U. Kolb, T. Gorelik, M. T. Otten, Towards automated diffraction tomography. Part II – Cell parameter determination. Ultramicroscopy 2008, 108, 763.CrossrefGoogle Scholar

  • [17]

    L. Seyfarth, J. Seyfarth, B. V. Lotsch, W. Schnick, J. Senker, Tackling the stacking disorder of melon–structure elucidation in a semicrystalline material. Phys. Chem. Chem. Phys. 2010, 12, 2227.CrossrefGoogle Scholar

  • [18]

    C. Martineau, J. Senker, F. Taulelle, NMR crystallography, annual reports on NMR spectroscopy. Annu. Reports NMR Spectrosc. 2014, 82, 1.Google Scholar

  • [19]

    M. Schmidt, C. S. Zehe, R. Siegel, J. U. Heigl, C. Steinlein, H.-W. Schmidt, J. Senker, NMR-crystallographic study of two-dimensionally self-assembled cyclohexane-based low-molecular-mass organic compounds. CrystEngComm 2013, 15, 8784.CrossrefGoogle Scholar

  • [20]

    M. Schmidt, J. J. Wittmann, R. Kress, D. Schneider, S. Steuernagel, H.-W. Schmidt, J. Senker, Crystal structure of a highly efficient clarifying agent for isotactic polypropylene. Cryst. Growth Des. 2012, 12, 2543.CrossrefGoogle Scholar

  • [21]

    F. Wöhler, J. F. von Liebig, Untersuchungen über das Radikal der Benzoesäure. Ann. Der Pharm. 1832, 3, 249.CrossrefGoogle Scholar

  • [22]

    B. R. Penfold, J. C. B. White, The crystal and molecular structure of benzamide. Acta Crystallogr. 1959, 12, 130.CrossrefGoogle Scholar

  • [23]

    J. Thun, L. Seyfarth, J. Senker, R. E. Dinnebier, J. Breu, Polymorphism in benzamide: Solving a 175-year-old riddle. Angew. Chem. Int. Edit. 2007, 46, 6729.CrossrefGoogle Scholar

  • [24]

    P. Ectors, D. Ectors, D. Zahn, Structure and interactions in benzamide molecular crystals. Mol. Simul. 2013, 39, 1079.CrossrefGoogle Scholar

  • [25]

    J. Thun, M. Schoeffel, J. Breu, Crystal structure prediction could have helped the experimentalists with polymorphism in benzamide. Mol. Simul. 2008, 34, 1359.CrossrefGoogle Scholar

  • [26]

    D. M. Benoit, P. Ectors, P. Duchstein, J. Breu, D. Zahn, A new polymorph (IV) of benzamide: structural characterization and mechanism of the I↔IV phase transition. Chem. Phys. Lett. 2011, 514, 274.CrossrefGoogle Scholar

  • [27]

    C. Butterhof, T. Martin, P. Ectors, D. Zahn, P. Niemietz, J. Senker, J. Breu, Thermoanalytical evidence of metastable molecular defects in form I of benzamide. Cryst. Growth Des. 2012, 12, 5365.CrossrefGoogle Scholar

  • [28]

    P. Giannozzi, S. Baroni, N. Bonini, M. Calandra, R. Car, C. Cavazzoni, D. Ceresoli, G. L. Chiarotti, M. Cococ-cioni, I. Dabo, A. Dal Corso, S. de Gironcoli, S. Fabris, G. Fratesi, R. Gebauer, U. Gerstmann, C. Gougous-sis, A. Kokalj, M. Lazzeri, L. Martin-Samos, N. Marzari, F. Mauri, R. Mazzarello, S. Paolini, A. Pasquarello, L. Paulatto, C. Sbraccia, S. Scandolo, G. Sclauzero, A. P. Seitsonen, A. Smogunov, P. Umari, R. M. Wentzcovitch, QUANTUM ESPRESSO: a modular and open-source software project for quantum simu-lations of materials. J. Phys. Condens. Matter 2009, 21, 395502.CrossrefGoogle Scholar

  • [29]

    P. Ectors, D. Zahn, Analysis of the molecular interactions governing the polymorphism of benzamide – a guide to syntheses? Phys. Chem. Chem. Phys. 2013, 15, 9219.CrossrefGoogle Scholar

  • [30]

    K. E. Johansson, J. van de Streek, Revision of the crystal structure of the first molecular polymorph in history. Cryst. Growth Des. 2016, 16, 1366.CrossrefGoogle Scholar

  • [31]

    W. I. F. David, K. Shankland, C. R. Pulham, N. Blagden, R. J. Davey, M. Song, Polymorphism in benzamide. Angew. Chem. Int. Edit. 2005, 44, 7032.CrossrefGoogle Scholar

  • [32]

    P. Ectors, P. Duchstein, D. Zahn, Nucleation mechanisms of a polymorphic molecular crystal: solvent-dependent structural evolution of benzamide aggregates. Cryst. Growth Des. 2014, 14, 2972.CrossrefGoogle Scholar

  • [33]

    J. Anwar, D. Zahn, Uncovering molecular processes in crystal nucleation and growth by using molecular simulation. Angew. Chem. Int. Ed. 2011, 50, 1996.CrossrefGoogle Scholar

  • [34]

    A. Kawska, J. Brickmann, R. Kniep, O. Hochrein, D. Zahn, An atomistic simulation scheme for modeling crystal formation from solution. J. Chem. Phys. 2006, 124, 024513.CrossrefGoogle Scholar

  • [35]

    P. Ectors, P. Duchstein, D. Zahn, From oligomers towards a racemic crystal: molecular simulation of DL -norleucine crystal nucleation from solution. CrystEngComm. 2015, 17, 6884.CrossrefGoogle Scholar

  • [36]

    P. Ectors, J. Anwar, D. Zahn, Two-step nucleation rather than self-poisoning: an unexpected mechanism of asymmetrical molecular crystal growth. Cryst. Growth Des. 2015, 15, 5118.CrossrefGoogle Scholar

  • [37]

    T. Milek, P. Duchstein, G. Seifert, D. Zahn, Motif reconstruction in clusters and layers: benchmarks for the kawska-zahn approach to model crystal formation. ChemPhysChem. 2010, 11, 847.CrossrefGoogle Scholar

  • [38]

    J. Bernstein, R. J. Davey, J.-O. Henck, Concomitant polymorphs. Angew. Chem. Int. Ed. 1999, 38, 3440.CrossrefGoogle Scholar

  • [39]

    J. Thun, L. Seyfarth, C. Butterhof, J. Senker, R. E. Dinnebier, J. Breu, Wöhler and Liebig revisited: 176 years of polymorphism in benzamide – and the story still continues! †. Cryst. Growth Des. 2009, 9, 2435.CrossrefGoogle Scholar

  • [40]

    T. Furuhara, T. Maki, Variant selection in heterogeneous nucleation on defects in diffusional phase transformation and precipitation. Mater. Sci. Eng. A 2001, 312, 145.CrossrefGoogle Scholar

  • [41]

    V. I. Levitas, B. F. Henson, L. B. Smilowitz, B. W. Asay, Solid-solid phase transformation via virtual melting significantly below the melting temperature. Phys. Rev. Lett. 2004, 92, 235702.CrossrefGoogle Scholar

  • [42]

    H. G. Brittain, Vibrational spectroscopic studies of cocrystals and salts. 1. The benzamide–benzoic acid system. Cryst. Growth Des. 2009, 9, 2492.CrossrefGoogle Scholar

  • [43]

    C. C. Seaton, A. Parkin, Making benzamide cocrystals with benzoic acids: the influence of chemical structure. Cryst. Growth Des. 2011, 11, 1502.CrossrefGoogle Scholar

  • [44]

    M. H. Levitt, D. M. Grant, R. K. Harris, J. Wiley, Symmetry-Based Pulse Sequences in Magic-Angle Spinning Solid-State NMR, 2002.Google Scholar

  • [45]

    M. Schmidt, J. J. Wittmann, R. Kress, H. Schmidt, J. Senker, Probing self-assembled 1,3,5-benzenetrisamides in isotactic polypropylene by 13C DQ solid-state NMR spectroscopy, Chem. Commun. 2013, 49, 267.CrossrefGoogle Scholar

  • [46]

    T. Gullion, J. Schaefer, Rotational-echo double-resonance NMR. J. Magn. Reson. 2011, 213, 413.CrossrefGoogle Scholar

  • [47]

    T. Gullion, Introduction to rotational-echo, double-resonance NMR. Concepts Magn. Reson. 1998, 10, 277.CrossrefGoogle Scholar

  • [48]

    M. Bak, J. T. Rasmussen, N. C. Nielsen, SIMPSON: a general simulation program for solid-state NMR spectroscopy. J. Magn. Reson. 2000, 147, 296.CrossrefGoogle Scholar

  • [49]

    A. L. Rohl, D. M. P. Mingos, The size and shape of molecular ions and their relevance to the packing of the hexafluorophosphate salts. J. Chem. Soc. Dalt. Trans. 1992, 3541.Google Scholar

  • [50]

    E. Lück, Chemical preservation of food. Zentralblatt für Bakteriol. Mikrobiol. und Hyg. 1. Abt. Orig. B, Hyg. 1985, 180, 311.Google Scholar

  • [51]

    R. Van Deun, J. Ramaekers, P. Nockemann, K. Van Hecke, L. Van Meervelt, K. Binnemans, Alkali-metal salts of aromatic carboxylic acids: liquid crystals without flexible chains. Eur. J. Inorg. Chem. 2005, 2005, 563.CrossrefGoogle Scholar

  • [52]

    C. Butterhof, T. Martin, W. Milius, J. Breu, Microphase separation with small amphiphilic molecules: crystal structure of preservatives sodium benzoate (E 211) and potassium benzoate (E 212). Z. Anorg. Allg. Chem. 2013, 639, 2816.CrossrefGoogle Scholar

  • [53]

    T. W. Martin, T. E. Gorelik, D. Greim, C. Butterhof, U. Kolb, J. Senker, J. Breu, Microphase separation upon crystallization of small amphiphilic molecules: “low” temperature form II of sodium benzoate (E 211). CrystEngComm. 2016, 18, 5811.CrossrefGoogle Scholar

  • [54]

    L. Leibler, Theory of microphase separation in block copolymers. Macromolecules 1980, 13, 1602.CrossrefGoogle Scholar

  • [55]

    H. J. Flammersheim, Physikalisch-chemische Untersuchungen am system Natriumbenzoat/Benzoesäure (III) Untersuchungen an der Tieftemperaturmodifikation des Komplexes 1 Natriumbenzoat · 2 Benzoesäure. Krist. Und Tech. 1974, 9, 313.CrossrefGoogle Scholar

  • [56]

    H. J. Flammersheim, Physikalisch-chemische Untersuchungen am system Natriumbenzoat/Benzoesäure (I) Infrarotspektropische und röntgenografische Untersuchungen bei Raumtemperatur. Krist. Und Tech. 1974, 9, 299.CrossrefGoogle Scholar

  • [57]

    H. J. Flammersheim, Physikalisch-chemische Untersuchungen am system Natriumbenzoat/Benzoesäure. J. Therm. Anal. 1975, 7, 571.CrossrefGoogle Scholar

  • [58]

    A. V. Trask, W. D. S. Motherwell, W. Jones, Solvent-drop grinding: green polymorph control of cocrystallisation. Chem. Commun. 2004, 890.Google Scholar

  • [59]

    C. Butterhof, W. Milius, J. Breu, Co-crystallisation of benzoic acid with sodium benzoate: the significance of stoichiometry. CrystEngComm. 2012, 14, 3945.CrossrefGoogle Scholar

  • [60]

    C. Butterhof, K. Bärwinkel, J. Senker, J. Breu, Polymorphism in co-crystals: a metastable form of the ionic co-crystal 2 HBz·1 NaBz crystallised by flash evaporation. CrystEngComm 2012, 14, 6744.CrossrefGoogle Scholar

  • [61]

    C. Butterhof, W. Milius, J. Breu, Influence of cation size on the co-crystallisation of benzoic acid with different benzoates. Z. Anorg. Allg. Chem. 2013, 639, 308.CrossrefGoogle Scholar

  • [62]

    J. M. Skinner, G. M. D. Stewart, J. C. Speakman, The crystal structure of the acid salts of some monobasic acids. Part III. Potassium hydrogen dibenzoate. J. Chem. Soc. 1954, 180.CrossrefGoogle Scholar

About the article

Received: 2016-06-10

Accepted: 2016-08-02

Published Online: 2016-08-17

Published in Print: 2017-02-01


Citation Information: Zeitschrift für Kristallographie - Crystalline Materials, Volume 232, Issue 1-3, Pages 55–67, ISSN (Online) 2196-7105, ISSN (Print) 2194-4946, DOI: https://doi.org/10.1515/zkri-2016-1977.

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