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Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.

ABSTRACT: To further our understanding of the role of solution chemistry in directing nucleation processes new experimental and computational data are presented on the solution and crystallisation chemistry of tolfenamic acid (TA), a benchmark polymorphic compound. With these, and previously published data, we were able to establish that TA is rapidly fluctuating between conformers in solution with either solvated monomers or dimers present depending on the solvent. Hence, despite the fact that conformational polymorphs can be obtained from crystallisations in ethanol, we found no links between solution chemistry and crystallisation outcomes. We discuss the implications of these conclusions for the nature of the nucleation pathway via dimers and clusters and raise experimental questions about how best to undertake relevant crystallisation studies.

SUBMITTER: Du W

PROVIDER: S-EPMC5814770 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.

Du W W Cruz-Cabeza A J AJ Woutersen S S Davey R J RJ Yin Q Q

Chemical science 20150417 6

To further our understanding of the role of solution chemistry in directing nucleation processes new experimental and computational data are presented on the solution and crystallisation chemistry of tolfenamic acid (TA), a benchmark polymorphic compound. With these, and previously published data, we were able to establish that TA is rapidly fluctuating between conformers in solution with either solvated monomers or dimers present depending on the solvent. Hence, despite the fact that conformati ...[more]

PMID: 29511513

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