Pushing Technique Boundaries to Probe Conformational Polymorphism.

Ward, Martin R; Taylor, Christopher R; Mulvee, Matthew T; Lampronti, Giulio I; Belenguer, Ana M; Steed, Jonathan W; Day, Graeme M; Oswald, Iain D H

Abstract

We present an extensive exploration of the solid-form landscape of chlorpropamide (CPA) using a combined experimental-computational approach at the frontiers of both fields. We have obtained new conformational polymorphs of CPA, placing them into context with known forms using flexible-molecule crystal structure prediction. We highlight the formation of a new polymorph (ζ-CPA) via spray-drying experiments despite its notable metastability (14 kJ/mol) relative to the thermodynamic α-form, and we identify and resolve the ball-milled η-form isolated in 2019. Additionally, we employ impurity- and gel-assisted crystallization to control polymorphism and the formation of novel multicomponent forms. We, thus, demonstrate the power of this collaborative screening approach to observe, rationalize, and control the formation of new metastable forms.

Citation

Ward, M. R., Taylor, C. R., Mulvee, M. T., Lampronti, G. I., Belenguer, A. M., Steed, J. W., …Oswald, I. D. H. (2023). Pushing Technique Boundaries to Probe Conformational Polymorphism. Crystal Growth and Design, 23(10), 7217-7230. https://doi.org/10.1021/acs.cgd.3c00641

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2023
• Online Publication Date: Aug 30, 2023
• Publication Date: Oct 1, 2023
• Deposit Date: Oct 25, 2023
• Publicly Available Date: Oct 25, 2023
• Journal: Crystal Growth and Design
• Print ISSN: 1528-7483
• Electronic ISSN: 1528-7505
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 10
• Pages: 7217-7230
• DOI: https://doi.org/10.1021/acs.cgd.3c00641
• Public URL: https://durham-repository.worktribe.com/output/1807777
• PMID: 37808905