British Association For Crystal Growth Annual Conference 2017
Magic-Angle Spinning NMR as an Effective Strategy to Study
Pressure-Induced Co-Crystallization Processes
Colan E. Hughes, Panukorn Phettrakul, P. Andrew Williams & Kenneth D. M. Harris
School of Chemistry, Cardiff University, Cardiff, CF10 3AT, U.K.
[email protected]
Introduction
Magic-angle spinning (MAS) is applied as a standard element in the acquisition of high-resolution solid-state
NMR spectra. A typical sample in a rotor with an outer diameter of 4 mm, spinning at a frequency of 12 kHz,
experiences a pressure at the walls of the rotor on the order of 100 atm. This pressure is typically assumed
to be too low to induce polymorphic transformations. However, with increasing interest in mechanochemistry,
we have identified MAS as a possible way to induce pressure (comparable to the pressures experienced by
a sample during grinding or milling) within an experimental set-up which facilitates in-situ measurement of
both liquid- and solid-state NMR spectra, following the CLASSIC NMR methodology [1]. Not only does this
procedure allow a quantifiable pressure range to be exerted on the sample, but it also provides a sample
environment in which temperature can be properly regulated. These features are in contrast to grinding and
milling processes, for which both pressure and temperature are very difficult to measure and control.
Assuming a rotor spinning at frequency ω and completely filled with a
sample of uniform density (ρ), the pressure at distance r from the
rotation axis of the rotor is given [2] by: p(r) = ½ω2r2ρ. Thus, the
sample experiences a pressure gradient, with ambient pressure at the
centre of the rotor, rising to a maximum pressure at the walls. Although
we may anticipate some redistribution of the powder sample upon
spinning, leading to a non-uniform density within the rotor, the
pressure gradient is expected to give rise to a range of environments
in our studies. We have applied this methodology to explore a number
of processes involving pressure-induced solid-state transformations,
including co-crystallization of different 1-haloadamantanes and cocrystallization of urea with α,ω-dihydroxyalkanes.
Co-Crystallization of 1-Haloadamantanes
A family of non-stoichiometric co-crystals composed of binary mixtures
of 1-haloadamantanes (Figure 1) has been discovered [3]. These cocrystals are solid solutions and have several distinct structure types,
only some of which match the structures of the pure components. In
particular, a 1:2 mixture of 1-Cl-adamantane and 1-I-adamantane
forms a solid solution with a structure type similar to 1-Br-adamantane
and distinct from the structure types of pure 1-Cl-adamantane and
pure 1-I-adamantane. The co-crystals can be produced by
crystallization from solution, from the melt and by mechanical grinding.
Figure 1. 1-Haloadamantane
We have carried out a series of experiments in which powders of two
different 1-haloadamantanes are mixed gently, before placing the
physical mixture in an NMR rotor and subjecting it to MAS. Acquisition
of solid-state 13C NMR spectra reveals the emergence of new peaks
due to formation of the co-crystal phase, as shown in Figure 2.
Co-Crystallization of Urea and α,ω-Dihydroxyalkanes
Figure 2. Part of the in-situ solidA series of co-crystals of urea and α,ω-dihydroxyalkanes of even chain
state 13C NMR spectra recorded
length [HO(CH2)nOH; n = 6, 8, 10, 12, 14, 16] was discovered some
as a function of time during
years ago [4]. Significantly, the crystal structures of these materials
co-crystal formation of
can be categorized into three well-defined structure types, without
1-Br-adamantane and
evidence of polymorphism for any member of the family. Whilst a solid1-I-adamantane under MAS.
state NMR study indicated [5] the transient existence of an
intermediate solid form during crystallization of urea and 1,10-dihydroxydecane from methanol solution, it
was only when milling was applied to physical mixtures of urea and either 1,6-dihydroxyhexane or
British Association For Crystal Growth Annual Conference 2017
1,8-dihydroxyoctane that polymorphism was revealed, with the discovery [6] of new, metastable polymorphs
with the A-P/O structure type, which had previously been observed only for α,ω-dihydroxyalkane/urea cocrystals with longer chain lengths (n = 10, 12, 14, 16) from solution-state crystallization. Table 1 summarizes
the known structure types.
urea +
A-P/A
A-P/O
1,6-dihydroxyhexane
Solution
Milling
1,8-dihydroxyoctane
Milling
1,10-dihydroxydecane
Solution
P/A
P/O
Solution
Table 1. Structure types observed for co-crystallization of urea with three different α,ω-dihydroxyalkanes. A-P
indicates anti-parallel urea ribbons, P indicates parallel urea ribbons, A indicates an acute angle between the
urea ribbon and the alkyl chain, O indicates an obtuse angle between the urea ribbon and alkyl chain. The
structure types are shown in Figure 3. Longer chains (n = 12, 14 and 16) give the A-P/O structure from solution
co-crystallization.
Figure 3. Schematic of the four well-defined structure types
observed for α,ω-dihydroxyalkane/urea co-crystals.
Figure 4. In-situ
1H
→ 13C CP NMR
As a transient intermediate solid form was observed by in-situ
spectra recorded as a function of time
solid-state NMR during the solution-state co-crystallization of
during co-crystallization of urea and
13C-urea and 1,10-dihydroxydecane, we wanted to see if new
1,6-dihydroxyhexane (with cooling from
70 °C to 20 °C during the first 8.2 hours).
polymorphs or other forms could be observed by mixing powder
samples of 13C-urea and α,ω-dihydroxyalkanes in an NMR rotor
and applying MAS (whilst acquiring in-situ 13C NMR spectra), under the expectation that the pressure
exerted by sample spinning may mimic the effects of milling. The results of one such experiment are shown
in Figure 4, in which a physical mixture of urea and 1,6-dihydroxyhexane was heated to melt the
1,6-dihydroxyhexane, then cooled while subjecting the sample to magic-angle spinning. Three peaks are
observed, one on the right due to pure urea and two overlapping peaks on the left due to urea in two distinct
polymorphs of the 1,6-dihydroxyhexane/urea co-crystal.
References
[1] C. E. Hughes, P. A. Williams & K. D. M. Harris, Angew. Chem. Int. Ed. 2014, 53, 8939.
[2] C. E. Hughes, P. A. Williams, V. L. Keast, V. G. Charalampopoulos, G. R. Edwards-Gau & K. D. M. Harris, Faraday
Discuss. 2015, 179, 115.
[3] P. Phettrakul, P. A. Williams & K. D. M. Harris, in preparation.
[4] J. Martí-Rujas, B. M. Kariuki, C. E. Hughes, A. Morte-Ródenas, F. Guo, Z. Glavcheva-Laleva, K. Taştemür, L. Ooi, L.
Yeo & K. D. M. Harris, New J. Chem. 2011, 35, 1515.
[5] C. E. Hughes, P. A. Williams, T. R. Peskett & K. D. M. Harris, J. Phys. Chem. Lett. 2012, 3, 3176.
[6] Y. Zhou, F. Guo, C. E. Hughes, D. L. Browne, T. R. Peskett & K. D. M. Harris, Cryst. Growth Des. 2015, 15, 2901.