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Direct Observation of Templated Two-Step Nucleation Mechanism during Olanzapine Hydrate Formation

Warzecha, M; Guo, R; Bhardwaj, RM; Reutzel-Edens, SM; Price, SL; Lamprou, DA; Florence, AJ; (2017) Direct Observation of Templated Two-Step Nucleation Mechanism during Olanzapine Hydrate Formation. Crystal Growth & Design , 17 (12) pp. 6382-6393. 10.1021/acs.cgd.7b01060. Green open access

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Abstract

Investigating crystal nucleation at the nanoscale is of significant interest, in particular, as more complex, nonclassical routes have roused questions about the classical view of homo- and heteronucleation processes. Here, we report the direct observation of a two-step nucleation mechanism during the transformation of anhydrous olanzapine to olanzapine dihydrate. Atomic force microscopy studies of the dominant (100)OZPNI face of olanzapine form I single crystals in contact with water show the formation and growth of dense nanodroplets concentrated at the steps. In unstirred solution, apparent ordering and crystallization from these droplets occur with olanzapine dihydrate D produced by the templating effect of the underlying olanzapine I lattice. In contrast, under stirred conditions a kinetic dihydrate polymorph, dihydrate B, nucleates probably due to the detachment of nanodroplets from the surface during stirring and a consequent loss of template effect. Computational modeling of the binding of olanzapine growth units on crystal step reveals many strongly bound dimer positions unrelated to either crystal structure. This impedes surface integration and contributes to the growth of disordered clusters at the ledge site. Nanocrystal modeling shows that the (100)OZPNI surface favors the nucleation of dihydrate D over the kinetic form. This work gives an important insight into heterogeneous two-step nucleation where the first step, the formation of a prenucleation droplet, can in the second step, bifurcate, either to produce the stable form by templating, or the kinetic form on detachment of the nanodroplets.

Type: Article
Title: Direct Observation of Templated Two-Step Nucleation Mechanism during Olanzapine Hydrate Formation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.cgd.7b01060
Publisher version: https://doi.org/10.1021/acs.cgd.7b01060
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Physical Sciences, Technology, Chemistry, Multidisciplinary, Crystallography, Materials Science, Multidisciplinary, Chemistry, Materials Science, ATOMIC-FORCE MICROSCOPY, HETEROGENEOUS NUCLEATION, SELECTIVE NUCLEATION, LUMAZINE SYNTHASE, SIZE DISTRIBUTION, GERM-FORMATION, CRYSTALS, CRYSTALLIZATION, CLUSTERS, EPITAXY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: http://discovery.ucl.ac.uk/id/eprint/10049608
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