Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers
Warzecha, Monika and Verma, Lakshmanji and Johnston, Blair F. and Palmer, Jeremy C. and Florence, Alastair J. and Vekilov, Peter G. (2020) Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers. Nature Chemistry, 12 (10). pp. 914-920. ISSN 1755-4330 (https://doi.org/10.1038/s41557-020-0542-0)
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Abstract
The symmetries of a crystal are notoriously uncorrelated to those of its constituent molecules. This symmetry breaking is typically thought to occur during crystallization. Here we demonstrate that one of the two symmetry elements of olanzapine crystals, an inversion centre, emerges in solute dimers extant in solution prior to crystallization. We combine time-resolved in situ scanning probe microscopy to monitor the crystal growth processes with all-atom molecular dynamics simulations. We show that crystals grow non-classically, predominantly by incorporation of centrosymmetric dimers. The growth rate of crystal layers exhibits a quadratic dependence on the solute concentration, characteristic of the second-order kinetics of the incorporation of dimers, which exist in equilibrium with a majority of monomers. We show that growth by dimers is preferred due to overwhelming accumulation of adsorbed dimers on the crystal surface, where it is complemented by dimerization and expedites dimer incorporation into growth sites. [Figure not available: see fulltext.].
ORCID iDs
Warzecha, Monika ORCID: https://orcid.org/0000-0001-6166-1089, Verma, Lakshmanji, Johnston, Blair F. ORCID: https://orcid.org/0000-0001-9785-6822, Palmer, Jeremy C., Florence, Alastair J. ORCID: https://orcid.org/0000-0002-9706-8364 and Vekilov, Peter G.;-
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Item type: Article ID code: 73815 Dates: DateEvent23 September 2020Published4 August 2020AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Strategic Research Themes > Advanced Manufacturing and MaterialsDepositing user: Pure Administrator Date deposited: 15 Sep 2020 09:58 Last modified: 25 Nov 2024 02:10 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/73815