Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers

Monika Warzecha, Lakshmanji Verma, Blair F. Johnston, Jeremy C. Palmer, Alastair J. Florence, Peter G. Vekilov

Research output: Contribution to journalArticle

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, which is complemented by dimerization on the surface and expedites dimer incorporation into growth sites.
Original languageEnglish
Number of pages37
JournalNature Chemistry
DOIs
Publication statusAccepted/In press - 4 Aug 2020

Keywords

  • dimers
  • Olanzapine
  • AFM imaging
  • crystal growth
  • molecular dynamic simulation

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    Data for: "Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers"

    Warzecha, M. (Creator), Verma, L. (Contributor), Johnston, B. (Supervisor), Palmer, J. (Supervisor), Florence, A. (Supervisor) & Vekilov, P. G. (Supervisor), University of Strathclyde, 14 Sep 2020

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    Prizes

    Gordon Conference Travel Award

    Warzecha, Monika (Recipient), 20 Jun 2019

    Prize: Prize (including medals and awards)

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