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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Martin T, Niemietz P, Greim D, Ectors P, Senker J, Zahn D, Breu J
Zeitschrift: Zeitschrift für Kristallographie
Jahr der Veröffentlichung: 2017
Band: 232
Heftnummer: 55-67
ISSN: 0044-2968


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 \textgreekp-stacking modes. Variations of hydrogen bonding versus \textgreekp-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.


FAU-Autoren / FAU-Herausgeber

Ectors, Philipp Dr.
Lehrstuhl für Theoretische Chemie
Zahn, Dirk Prof. Dr.
Professur für Theoretische Chemie


Zusätzliche Organisationseinheit(en)
Exzellenz-Cluster Engineering of Advanced Materials


Autor(en) der externen Einrichtung(en)
Universität Bayreuth


Zitierweisen

APA:
Martin, T., Niemietz, P., Greim, D., Ectors, P., Senker, J., Zahn, D., & Breu, J. (2017). Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts. Zeitschrift für Kristallographie, 232(55-67). https://dx.doi.org/10.1515/zkri-2016-1977

MLA:
Martin, Thomas, et al. "Fundamental theoretical and practical investigations of the polymorph formation of small amphiphilic molecules, their co-crystals and salts." Zeitschrift für Kristallographie 232.55-67 (2017).

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Zuletzt aktualisiert 2019-16-03 um 18:23