Solid state phase studies via 3D electron and high pressure X-ray diffraction
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Date
10/06/2022Author
Broadhurst, Edward
Metadata
Abstract
The study of crystals and associated phase transitions has numerous
applications in areas such as energy storage, optoelectronics and
pharmaceuticals. Understanding and characterizing these crystals is central to
any solid-state research activity and the screening of different polymorphs is
an expensive and time-consuming activity. Recent improvements to hardware
and software have fuelled developments in electron crystallography, where
crystal structures from crystals with dimensions of less than 1 micron is
possible. Presently, there are over 150 small molecular structures deposited on
the Cambridge Structural Database and this number is rapidly increasing. An
attractive feature of electron diffraction is the strong interaction of electrons
with matter which allows characterization of sub-micron sized crystals as well
as routine location of H atoms in the resulting Fourier difference map. One
drawback is that as result of this strong interaction, the diffraction patterns can
exhibit dynamical effects caused by multiple scattering events.
Chapter 2 outlines a comprehensive and detailed workflow for
collecting 3D electron diffraction (3D ED) data via the continuous rotation
method on a Tecnai F20 transmission electron microscope. This
developmental chapter describes sample preparation, data collection, and
hardware and software usage. Successful data collection is detailed as well as
structure refinement. Further developments and upgrades are also proposed
to optimise the platform for routine data collection on micron and sub-micron
crystallites.
Chapter 3 details how 3DED has been used to follow polymorph
evolution in the crystallization of glycine from aqueous solution. The three
polymorphs of glycine which exist under ambient conditions follow the
stability order β < α < γ. The least stable β polymorph forms within the first
three minutes, but this begins to yield the α-form after only one minute more.
Both structures could be determined from continuous rotation electron
diffraction data collected in less than 20 seconds on crystals of thickness ∼100
nm. Even though the γ-form is thermodynamically the most stable
polymorph, kinetics favours the α-form, which dominates after prolonged
standing. In the same sample, some β and one crystallite of the γ polymorph
were also observed.
Chapter 4 details how time-resolved carbamazepine crystallization
from wet (‘bench‘) ethanol has been monitored using a combination of
cryoTEM and 3D ED. Carbamazepine is shown to crystallize exclusively as a
dihydrate after 180 seconds. When the timescale was reduced to 30 seconds,
three further polymorphs could be identified. At 20 seconds, the development
of early-stage carbamazepine dihydrate was observed through phase
separation. This work reveals two possible crystallization pathways present in
this active pharmaceutical ingredient.
Chapter 5 is a study of the crystal structure of Blatter’s radical (1,3-
diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) investigated between
ambient pressure and 6.07 GPa. The sample remains in a compressed form of
the ambient pressure phase up to 5.34 GPa, the largest direction of strain being
parallel to direction of π-stacking interactions. The bulk modulus is 7.4(6) GPa,
with a pressure derivative equal to 9.33(11). As pressure increases, the phenyl
groups attached to the N1 and C3 positions of the triazinyl moieties of
neighbouring pairs of molecules approach each other, causing the former to
begin to rotate between 3.42 to 5.34 GPa. The onset of the phenyl rotation may
be interpreted as a second order phase transition which introduces a new
mode for accommodating pressure. It is premonitory to a first order,
isosymmetric phase transition which occurs on increasing pressure from 5.34
to 5.54 GPa. Although the phase transition is driven by volume minimisation,
rather than relief of unfavourable contacts, it is accompanied by a sharp jump
in the orientation of the rotation angle of the phenyl group. DFT calculations
suggest that the adoption of a more planar conformation by the triazinyl
moiety at the phase transition is owed to relief of intramolecular H∙∙∙H contacts
at the transition. Although no dimerization of the radicals occurs, the π-
stacking interactions are compressed by 0.341(3) Å between ambient pressure
and 6.07 GPa.
Chapter 6 details the response of two different polymorphs of Blatter’s
radical derivatives to increasing pressure. The polymorphs’ principal
differences are centred around how the π-stacks are formed from their
respective symmetry elements, causing differences in the distribution of voids.
Under increasing pressure, there is continuous change in the lattice
parameters, with substantial compression via the π-stacks present in both
polymorphs. Further analyses of the interacting dimers and unit-cell volume
partitioning via Monte Carlo procedures reveal a subtle second order phase
transition at 2.84 GPa. Preliminary calculations suggest the π-stacks’
compressibility in both polymorphs is due to the volume minimisation and
hence free energy contribution.