marketplace for club goers. The rationale for investigating materials using pressure
to this point was to find new polymorphs of pharmaceuticals, but the area of illicit
materials had been overlooked despite the unregulated nature of production of these
materials; the potential for the discovery of new forms was and is still very high.
Mephedrone was one of the ‘legal highs’ of choice hence we investigated the
hydrogen sulphate salt of this material [141]. We observed that mephedrone hydrogen sulphate was quite polymorphic on compression and that the phase transitions to
the two new high-pressure polymorphs were single-crystal to single-crystal which
enabled ease of characterisation. The first phase transformation was between 0.5 and
0.88 GPa and was isomorphous with a compression of the unit cell volume by 10%.
This was enabled by the change in the orientation of the sulphate chains, whilst there
was a small shift in the organic counterion. The second phase transition occurs
between 3.56 and 4.8 GPa with a reduction in the symmetry to P-1 and increase in Z
0
to 4 which made the refinement of the model challenging. This phase transition is
characterised by a marked reorientation in the sulphate chains but also in the
torsional angles in the mephedrone molecule itself. In many of the studies at pressure
we have observed that hydrogen bonding lengths are limited to the ambient pressure
values in the CSD but this case we were able to demonstrate that this in also the case
for phenyl-phenyl interactions. Prior to the phase transition, the phenyl groups of the
mephedrone molecule are compressed to the lower limits observed in the database
before the transition. After the transition two out of the four interactions move
substantially away from the limit.
We followed with a study of 3,4-methylenedioxymethamphetamine hydrochloride or MDMA [129]. Disappointingly, there were no phase transitions observed in
this system; however, one of the key findings was that due to the orientation of the
molecules with respect to each other, there was a correlation with respect to the
principal axis of strain where the compression of one axis limited the compression
along another like a wine rack effect which had been observed previously in relation
to metal-organic framework materials [142]. Furthermore, the orientation of the
hydrogen bonds allowed for the structure to be compressed easily in that direction
as they acted like a spring which may have attributed to the system not showing any
polymorphism with pressure. We have recently noted this spring-like effect in the
compression of two high-pressure polymorphs of ε-caprolactam [139]. The two
forms have similar hydrogen-bonded chains; however, the interconnectivity of
neighbouring chains is different. We noted a large compressibility along the chains
where the neighbours were not intercalated, but this was reduced by half in the
polymorph where there was intercalation.
Overall, we see a wide range of behaviours in organic molecular compounds
under high-pressure conditions. The overriding message from this is that the interaction of the PTM can have a huge impact on the ability to observe new phases of
molecular forms. Hence the planning and preparation for high-pressure studies is
crucial for a successful outcome. The high degree of flexibility can create issues for
the molecular transformations, and the kinetics of such can be very slow or
suppressed completely. Whilst we have only provided a few examples of molecular
materials at high pressure, these have been largely focussed on single-crystal
Crystallography Under High Pressures
177
to this point was to find new polymorphs of pharmaceuticals, but the area of illicit
materials had been overlooked despite the unregulated nature of production of these
materials; the potential for the discovery of new forms was and is still very high.
Mephedrone was one of the ‘legal highs’ of choice hence we investigated the
hydrogen sulphate salt of this material [141]. We observed that mephedrone hydrogen sulphate was quite polymorphic on compression and that the phase transitions to
the two new high-pressure polymorphs were single-crystal to single-crystal which
enabled ease of characterisation. The first phase transformation was between 0.5 and
0.88 GPa and was isomorphous with a compression of the unit cell volume by 10%.
This was enabled by the change in the orientation of the sulphate chains, whilst there
was a small shift in the organic counterion. The second phase transition occurs
between 3.56 and 4.8 GPa with a reduction in the symmetry to P-1 and increase in Z
0
to 4 which made the refinement of the model challenging. This phase transition is
characterised by a marked reorientation in the sulphate chains but also in the
torsional angles in the mephedrone molecule itself. In many of the studies at pressure
we have observed that hydrogen bonding lengths are limited to the ambient pressure
values in the CSD but this case we were able to demonstrate that this in also the case
for phenyl-phenyl interactions. Prior to the phase transition, the phenyl groups of the
mephedrone molecule are compressed to the lower limits observed in the database
before the transition. After the transition two out of the four interactions move
substantially away from the limit.
We followed with a study of 3,4-methylenedioxymethamphetamine hydrochloride or MDMA [129]. Disappointingly, there were no phase transitions observed in
this system; however, one of the key findings was that due to the orientation of the
molecules with respect to each other, there was a correlation with respect to the
principal axis of strain where the compression of one axis limited the compression
along another like a wine rack effect which had been observed previously in relation
to metal-organic framework materials [142]. Furthermore, the orientation of the
hydrogen bonds allowed for the structure to be compressed easily in that direction
as they acted like a spring which may have attributed to the system not showing any
polymorphism with pressure. We have recently noted this spring-like effect in the
compression of two high-pressure polymorphs of ε-caprolactam [139]. The two
forms have similar hydrogen-bonded chains; however, the interconnectivity of
neighbouring chains is different. We noted a large compressibility along the chains
where the neighbours were not intercalated, but this was reduced by half in the
polymorph where there was intercalation.
Overall, we see a wide range of behaviours in organic molecular compounds
under high-pressure conditions. The overriding message from this is that the interaction of the PTM can have a huge impact on the ability to observe new phases of
molecular forms. Hence the planning and preparation for high-pressure studies is
crucial for a successful outcome. The high degree of flexibility can create issues for
the molecular transformations, and the kinetics of such can be very slow or
suppressed completely. Whilst we have only provided a few examples of molecular
materials at high pressure, these have been largely focussed on single-crystal
Crystallography Under High Pressures
177