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Serendipitous isolation of a disappearing conformational polymorph of succinic acid challenges computational polymorph prediction

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Abstract

A conformational polymorph (γ) of succinic acid was discovered in an attempt to purify a leucine dipeptide by cocrystallization from a methanol solution in the presence of various impurities, such as trifluoroacetic acid. The new γ-form was found to have crystallized concomitantly with the most stable β form. In light of this situation, a crystal structure prediction study was undertaken to examine the polymorph landscape. These studies reveal that the γ polymorph is thermodynamically competitive with the other observed polymorphs; having a more stable folded conformation than the planar crystalline conformation in the β form, but being stabilized less by the intermolecular interactions. Simulations and experiment show that the folded conformation is dominant in solution, but that trapping long-lived crystals of the new metastable polymorph may be challenging. Thus the γ polymorph provides a stringent test of theories for predicting which thermodynamically plausible structures may be practically important polymorphs.

Graphical abstract: Serendipitous isolation of a disappearing conformational polymorph of succinic acid challenges computational polymorph prediction

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Publication details

The article was received on 18 Apr 2018, accepted on 30 May 2018 and first published on 30 May 2018


Article type: Paper
DOI: 10.1039/C8CE00625C
Citation: CrystEngComm, 2018, Advance Article
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    Serendipitous isolation of a disappearing conformational polymorph of succinic acid challenges computational polymorph prediction

    P. Lucaioli, E. Nauha, I. Gimondi, L. S. Price, R. Guo, L. Iuzzolino, I. Singh, M. Salvalaglio, S. L. Price and N. Blagden, CrystEngComm, 2018, Advance Article , DOI: 10.1039/C8CE00625C

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