concentrations the Form III or the dihydrate could be isolated. The latter observation
of the dihydrate is interesting as the lower concentration enabled precipitation at
higher pressure to isolate the hydrated form. They had to crystallise the solvent as
ice-VI at 1.6 GPa before decompression to remove ice and heat annealing of the
piracetam powder. Paracetamol dihydrate and piracetam dihydrate can both be
formed through the crystallisation of the solvent before decompression to reveal a
powder that can be annealed. In each of these cases, ice-VI could be acting as a
nucleator and templating the hydrate. This is supported to some extent by the
crystallisation of Form IV using more concentrated aqueous solution that precipitates at lower pressures. Alternatively, in a study of γ-aminobutyric acid, Fabbiani
and co-workers were able to provide computational evidence to support the
stabilisation of the hydrate over the pure compound; hence, the hydrate is the
favoured product at pressure [45]. This idea is certainly worth exploring given
γ-aminobutyric acid hydrate is recoverable to ambient pressure and hydration may
be a route to provide stable forms of pharmaceutical products. The tuning of
experimental conditions in this way demonstrates the complexity of the highpressure recrystallisation experiment and the potential to realise novel polymorphs
and solvates of materials under these conditions.
2.2.4 Compression
The previous topics have described how the compound or solvent can be manipulated to isolate new solid forms of materials at fairly low pressures. They have been
limited to lower pressures due to the melting point of the compound of study or the
freezing pressures of the solvent in which the solute has been dissolved. Compression studies have been the standard method to investigate materials at high pressure.
These studies can provide evidence of how intermolecular interactions evolve over a
pressure range or whether the physical properties of a material may change. The
changes to the experimental set-up for these experiments are limited to the geometry
of the sample environment. The gasket hole size and thickness of gasket are altered
depending on the pressures that need to be achieved. The choice of PTM is also
critical to ensure hydrostaticity of compression, but it can play a large role in how the
compound of study reacts to pressure changes. In this section, we would like to
highlight two recent studies that have demonstrated that compression studies are not
routine and that changing PTM can alter the behaviour of molecular materials at
pressure. This will be explored further in Sect. 4.5 highlighting metal-organic
materials at high pressure.
Collings and Hanfland have recently investigated 4-hydroxycyanobenzene in
relation to charge transport properties for semiconductors and how pressure can
play a role in changing the intermolecular interactions and hence the properties of the
material [49]. In their study they noticed that the PTM was playing a role in the
formation of new host-guest phases of 4-hydroxycyanobenzene. The insertion of
PTMs into the crystal structure is quite unusual for organic structures that do not
possess a channel structure, but it is well-known in metal-organic framework
Crystallography Under High Pressures
151
of the dihydrate is interesting as the lower concentration enabled precipitation at
higher pressure to isolate the hydrated form. They had to crystallise the solvent as
ice-VI at 1.6 GPa before decompression to remove ice and heat annealing of the
piracetam powder. Paracetamol dihydrate and piracetam dihydrate can both be
formed through the crystallisation of the solvent before decompression to reveal a
powder that can be annealed. In each of these cases, ice-VI could be acting as a
nucleator and templating the hydrate. This is supported to some extent by the
crystallisation of Form IV using more concentrated aqueous solution that precipitates at lower pressures. Alternatively, in a study of γ-aminobutyric acid, Fabbiani
and co-workers were able to provide computational evidence to support the
stabilisation of the hydrate over the pure compound; hence, the hydrate is the
favoured product at pressure [45]. This idea is certainly worth exploring given
γ-aminobutyric acid hydrate is recoverable to ambient pressure and hydration may
be a route to provide stable forms of pharmaceutical products. The tuning of
experimental conditions in this way demonstrates the complexity of the highpressure recrystallisation experiment and the potential to realise novel polymorphs
and solvates of materials under these conditions.
2.2.4 Compression
The previous topics have described how the compound or solvent can be manipulated to isolate new solid forms of materials at fairly low pressures. They have been
limited to lower pressures due to the melting point of the compound of study or the
freezing pressures of the solvent in which the solute has been dissolved. Compression studies have been the standard method to investigate materials at high pressure.
These studies can provide evidence of how intermolecular interactions evolve over a
pressure range or whether the physical properties of a material may change. The
changes to the experimental set-up for these experiments are limited to the geometry
of the sample environment. The gasket hole size and thickness of gasket are altered
depending on the pressures that need to be achieved. The choice of PTM is also
critical to ensure hydrostaticity of compression, but it can play a large role in how the
compound of study reacts to pressure changes. In this section, we would like to
highlight two recent studies that have demonstrated that compression studies are not
routine and that changing PTM can alter the behaviour of molecular materials at
pressure. This will be explored further in Sect. 4.5 highlighting metal-organic
materials at high pressure.
Collings and Hanfland have recently investigated 4-hydroxycyanobenzene in
relation to charge transport properties for semiconductors and how pressure can
play a role in changing the intermolecular interactions and hence the properties of the
material [49]. In their study they noticed that the PTM was playing a role in the
formation of new host-guest phases of 4-hydroxycyanobenzene. The insertion of
PTMs into the crystal structure is quite unusual for organic structures that do not
possess a channel structure, but it is well-known in metal-organic framework
Crystallography Under High Pressures
151