Pushing technique boundaries to probe conformational polymorphism

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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
16 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)7217-7230
Number of pages14
JournalCrystal Growth and Design
Volume23
Issue number10
Early online date30 Aug 2023
DOIs
Publication statusPublished - 4 Oct 2023

Keywords

  • polymorphism
  • chlorpropamide
  • crystal structure calculation
  • milling
  • gels
  • spray drying

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