Switching Polymorph Stabilities with Impurities: A Thermodynamic Route to Benzamide Form III

10.26434/chemrxiv.13138964.v1 ◽

2020 ◽

Author(s):

Weronika Kras ◽

Andrea Carletta ◽

Riccardo Montis ◽

Rachel Sullivan ◽

Aurora J. Cruz-Cabeza

Keyword(s):

Solid Solutions ◽

Polymorphic Behavior ◽

Polymorphic Forms

We investigate the polymorphic behavior of benzamide, the first compound known to exhibit polymorphism, in the presence of small amounts of nicotinamide in the crystallization environment. A previous study by Emmerling et al.<sup>1</sup> showed that the presence of nicotinamide promotes the transformation of the thermodynamic polymorph I of benzamide into its metastable polymorph III via mechanochemistry. We show that this transformation is the result of a thermodynamic switch between these two polymorphic forms driven by the formation of solid solutions with a small amount of nicotinamide. The presence of nicotinamide in the crystallization environment promotes the robust and exclusive crystallization of the elusive form III. These results represent a promising route to the synthesis and utilization of elusive polymorphs of pharmaceutical interest.

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Switching polymorph stabilities with impurities provides a thermodynamic route to benzamide form III

Communications Chemistry ◽

10.1038/s42004-021-00473-7 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Weronika Kras ◽

Andrea Carletta ◽

Riccardo Montis ◽

Rachel A. Sullivan ◽

Aurora J. Cruz-Cabeza

Keyword(s):

Solid Solutions ◽

Polymorphic Forms

AbstractAlmost 200 years ago, benzamide was reported as polymorphic with two of its forms (II and III) found to be difficult to crystallise. In a recent study, it was shown that benzamide form I can easily convert into benzamide form III using mechanochemistry in the presence of nicotinamide. Here we show, experimentally and computationally, that this transformation is the result of a thermodynamic switch between these two polymorphic forms driven by the formation of solid solutions with small amounts of nicotinamide. The presence of nicotinamide in the crystallisation environment promotes the robust and exclusive crystallisation of the elusive form III. These results represent a promising route to the synthesis and utilisation of elusive polymorphs of pharmaceutical interest.

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Polymorphic phase transition of a membrane protein - analysis of continuous diffuse electron diffraction intensity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142451 ◽

1986 ◽

Vol 44 ◽

pp. 166-167

Author(s):

Douglas L. Dorset ◽

Andrew K. Massalski

Keyword(s):

Molecular Sieve ◽

Three Dimensional ◽

Pore Geometry ◽

Two Dimensional ◽

Diffraction Intensity ◽

Polymorphic Phase Transition ◽

E Coli ◽

Crystallographic Study ◽

Hexagonal Form ◽

Polymorphic Forms

Matrix porin, the ompF gene product of E. coli, has been the object of a electron crystallographic study of its pore geometry in an attempt to understand its function as a membrane molecular sieve. Three polymorphic forms have been found for two-dimensional crystals reconstituted in phospholipid, two hexagonal forms with different lipid content and an orthorhombic form coexisting with and similar to the hexagonal form found after lipid loss. In projection these have been shown to retain the same three-fold pore triplet geometry and analyses of three-dimensional data reveal that the small hexagonal and orthorhombic polymorphs have similar structure as well as unit cell spacings.

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