Pharmaceutical Polymorph Control in a Drug-Mimetic Supramolecular Gel

Foster, Jonathan A.; Damodaran, Krishna K.; Maurin, Antoine; Day, Graeme M.; Thompson, Hugh P.G.; Cameron, Gary J.; Bernal, Jenifer Cuesta; Steed, Jonathan W.

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 experimetns give the yellow form. Conformational and crystal structure prediction methods have been used to propose the structure of the gel and shows that the templation of the red form by the targetted gel results from conformational matching of the gelator to the ROY substrate coupled with overgorwth of ROY onto the the local periodic structure of the gel fibres.

Citation

Foster, J. A., Damodaran, K. K., Maurin, A., Day, G. M., Thompson, H. P., Cameron, G. J., …Steed, J. W. (2017). Pharmaceutical Polymorph Control in a Drug-Mimetic Supramolecular Gel. Chemical Science, 8(1), 78-84. https://doi.org/10.1039/c6sc04126d

• Journal Article Type: Article
• Acceptance Date: Oct 6, 2016
• Online Publication Date: Oct 7, 2016
• Publication Date: Jan 1, 2017
• Deposit Date: Oct 10, 2016
• Publicly Available Date: Oct 10, 2016
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Electronic ISSN: 2041-6539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• Pages: 78-84
• DOI: https://doi.org/10.1039/c6sc04126d
• Public URL: https://durham-repository.worktribe.com/output/1403160