TY - JOUR
T1 - Understanding the agglomerate crystallisation of hexamine through X-ray microscopy and crystallographic modelling
AU - Nguyen, Thai T.H.
AU - Gajjar, Parmesh
AU - Sun, Jun
AU - Hammond, Robert B.
AU - Murnane, Darragh
AU - Tordoff, Benjamin
AU - Lauridsen, Erik
AU - Withers, Philip J.
AU - Roberts, Kevin J.
N1 - Funding Information:
This work forms part of the research from the INFORM2020 consortium, which was funded through EPSRC grant EP/N025075/1 “Molecules to manufacture: Processing and Formulation Engineering of Inhalable Nanoaggregates and Micro-particles”. We are gratefully acknowledge James Carr and Berzah Yavuzyegit for technical assistance with LabDCT and acknowledge additional funding for this study by Carl Zeiss Microscopy. This work also builds upon research on morphological modelling supported by EPSRC grant EP/I028293/1 “HABIT – Crystal morphology from crystallographic and growth environment factors” and the related Synthonic Engineering programme supported by Pfizer, Boeringer-Ingellheim, Novartis and Syngenta. PG acknowledges support from EP/M010619/1. Beamtime was kindly provided by the Henry Moseley X-ray Imaging Facility (HMXIF), which was established through EPSRC grants EP/F007906/1, EP/I02249X/1 and EP/F028431/1, which is now part of the National Research facility in X-ray CT funded through EPSRC grant EP/T02593X/1. HMXIF is also a part of the Henry Royce Institute for Advanced Materials which was established through EPSRC grants EP/R00661X/1, EP/P025498/1 and EP/P025021/1.
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/2/1
Y1 - 2023/2/1
N2 - The detailed molecular-scale mechanism of the growth of organic crystals underpins a diversity of phenomena, such as the isolation and purification of high-quality materials for the pharmaceutical and fine chemical sectors. Recent advances in X-ray Microscopy (XRM) and complementary diffraction contrast tomography (DCT) have enabled the detailed characterisation of the micro-structure of hexamine agglomerates. Detailed XRM analysis of the growth history and micro-structure of such agglomerates reveals a highly orientated epitaxial inter-relationship between their constituent micro-crystallites. This is found to be consistent with a secondary nucleation growth mechanism associated with re-growth at the 3-fold corner sites within the crystals’ dominant {1 1 0} dodecahedral morphology. The agglomeration appears to heal upon further growth as the aligned agglomerated micro-crystals connect and fuse together but, in doing so, pockets of inter-crystallite mother liquor become trapped forming a symmetric pattern of solvent inclusions. The mechanistic origin of this phenomenon is rationalised with respect to historical data together with an analysis of the solid-state chemistry of the compound through the development of a ‘snow flake’ model. The latter draws upon hexamine's propensity for edge growth instabilities with increasing crystal size as well as its tendency for unstable growth at the facet corners along the 〈1 1 1〉 directions, a situation compounded by the lack of growth-promoting dislocations at the centers of the {1 1 0} habit surfaces. The agglomerative mechanism presented here could apply to other high symmetry crystal systems, particularly those whose crystal structures involve centred Bravais lattices and where the dominant inter-molecular interactions are angled towards the facet edges.
AB - The detailed molecular-scale mechanism of the growth of organic crystals underpins a diversity of phenomena, such as the isolation and purification of high-quality materials for the pharmaceutical and fine chemical sectors. Recent advances in X-ray Microscopy (XRM) and complementary diffraction contrast tomography (DCT) have enabled the detailed characterisation of the micro-structure of hexamine agglomerates. Detailed XRM analysis of the growth history and micro-structure of such agglomerates reveals a highly orientated epitaxial inter-relationship between their constituent micro-crystallites. This is found to be consistent with a secondary nucleation growth mechanism associated with re-growth at the 3-fold corner sites within the crystals’ dominant {1 1 0} dodecahedral morphology. The agglomeration appears to heal upon further growth as the aligned agglomerated micro-crystals connect and fuse together but, in doing so, pockets of inter-crystallite mother liquor become trapped forming a symmetric pattern of solvent inclusions. The mechanistic origin of this phenomenon is rationalised with respect to historical data together with an analysis of the solid-state chemistry of the compound through the development of a ‘snow flake’ model. The latter draws upon hexamine's propensity for edge growth instabilities with increasing crystal size as well as its tendency for unstable growth at the facet corners along the 〈1 1 1〉 directions, a situation compounded by the lack of growth-promoting dislocations at the centers of the {1 1 0} habit surfaces. The agglomerative mechanism presented here could apply to other high symmetry crystal systems, particularly those whose crystal structures involve centred Bravais lattices and where the dominant inter-molecular interactions are angled towards the facet edges.
KW - A1. Computer simulation
KW - A1. Morphological stability
KW - A1. Supersaturated solutions
KW - A1. X-Ray computed tomography
KW - A2. Growth from solutions
UR - http://www.scopus.com/inward/record.url?scp=85145550926&partnerID=8YFLogxK
U2 - 10.1016/j.jcrysgro.2022.126986
DO - 10.1016/j.jcrysgro.2022.126986
M3 - Article
AN - SCOPUS:85145550926
VL - 603
JO - Journal of Crystal Growth
JF - Journal of Crystal Growth
SN - 0022-0248
M1 - 126986
ER -