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Pharmaceutical polymorph control in a drug-mimetic supramolecular gel.

ABSTRACT: We report the synthesis of a bis(urea) gelator designed to specifically mimic the chemical structure of the highly polymorphic drug substance ROY. Crystallization of ROY from toluene gels of this gelator results in the formation of the metastable red form instead of the thermodynamic yellow polymorph. In contrast, all other gels and solution control experiments give the yellow form. Conformational and crystal structure prediction methods have been used to propose the structure of the gel and show that the templation of the red form by the targeted gel results from conformational matching of the gelator to the ROY substrate coupled with overgrowth of ROY onto the local periodic structure of the gel fibres.

SUBMITTER: Foster JA

PROVIDER: S-EPMC5304659 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Pharmaceutical polymorph control in a drug-mimetic supramolecular gel.

Foster Jonathan A JA Damodaran Krishna K KK Maurin Antoine A Day Graeme M GM Thompson Hugh P G HPG Cameron Gary J GJ Bernal Jenifer Cuesta JC Steed Jonathan W JW

Chemical science 20161007 1

We report the synthesis of a bis(urea) gelator designed to specifically mimic the chemical structure of the highly polymorphic drug substance ROY. Crystallization of ROY from toluene gels of this gelator results in the formation of the metastable red form instead of the thermodynamic yellow polymorph. In contrast, all other gels and solution control experiments give the yellow form. Conformational and crystal structure prediction methods have been used to propose the structure of the gel and sho ...[more]

PMID: 28451150

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