journal article·2023-10-04Open access

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

Crystal Growth & Design· Volume 23· Issue 10

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Crystallography and molecular interactions · Crystallization and Solubility Studies · Machine Learning in Materials Science

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, U.K.

Computational Systems Chemistry, School of Chemistry, University of Southampton, Southampton SO17 1BJ, U.K.

Department of Chemistry, Durham University, South Road, Durham DH1 3LE, U.K.

Department of Materials Science & Metallurgy, University of Cambridge, 27 Charles Babbage Rd, Cambridge CB3 0FS, U.K.

Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Funding

Engineering and Physical Sciences Research Council

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