Phase stability in molecular materials at extreme conditions of temperature and pressure

Understanding phase stability and polymorphism in molecular materials is of importance in applications such as energy storage, optoelectronics and pharmaceuticals. The pharmaceutical industry invests billions of pounds every year on the investigation of new polymorphs of drugs, on modelling their thermodynamics and predicting their existence. The topic is also well known in planetary science, where the thermal and mechanical behaviour of "molecular ices" yields important constraints for modelling their deposits in extra-terrestrial settings. In this thesis, the response of crystalline molecular materials is studied using different X-ray and neutron diffraction techniques between 0 - 7 GPa and 5 - 465 K. The results are interpreted with the aid of semi-empirical and ab initio computational data. Neutrons have been fundamental and consistently used for their accuracy in locating H-atoms, which mediate many of the intermolecular interactions in the crystal structures studied in this work. Chapter 2 explores the effect of pressure on the crystal structures of the two ambient-pressure polymorphs of the amino acid L-histidine. Diffraction measurements performed on the small-molecule single-crystal diffraction beamline I19 at the Diamond Light Source (UK), up to 6.60 GPa for the orthorhombic form I (P212121) and 6.85 GPa for the monoclinic form II (P21), show their crystal structures undergo isosymmetric single-crystal-to-single-crystal first-order phase transitions at 4.5 GPa and 3.1 GPa to forms I' and II', respectively. Although the similarity in crystal packing and intermolecular interaction energies between the polymorphs is remarkable at ambient conditions, the manner in which each polymorph responds to pressure is different. The order of compressibility follows the densities of the polymorphs at ambient conditions (1.450 and 1.439 g cm−3 for phases I and II, respectively). Form II is found to be softer than form I, with bulk moduli of 11.6(6) GPa and 14.0(5) GPa, respectively. The difference is also related to the different space-group symmetry, the softer monoclinic form having more degrees of freedom available to accommodate the change in pressure. In the orthorhombic form, the imidazole-based H-atom involved in the H-bond along the c-direction swaps the acceptor O-atom at the transition to phase I'; the same swap occurs just after the phase transition in the monoclinic form and is also preceded by a bifurcation. Concurrently, the H-bond and the long-range electrostatic interaction along the b-direction form a three-centred H bond at the I to I' transition, while they swap their character during the II to II' transition. The structural data were interpreted using periodic-density-functional theory, symmetry-adapted perturbation theory and semi-empirical Pixel calculations, which indicate that the transition is driven by minimisation of volume, the intermolecular interactions generally being destabilised by the phase transitions. Nevertheless, volume calculations are used to show that networks of intermolecular contacts in both phases are very much less compressible than the interstitial void spaces, having bulk moduli similar to moderately hard metals. The volume of the networks changes only slightly over the course of both phase transitions, with the overall unit-cell-volume decrease occurring through larger compression of interstitial void space. The thesis continues investigating the two polymorphs of the amino acid L-histidine in the low-temperature regime. In Chapter 3, the structure of the monoclinic form is determined for the first time by single-crystal neutron diffraction and that of the orthorhombic polymorph is reinvestigated with an un-twinned crystal, improving experimental precision and accuracy. For each polymorph, data were collected using the Koala Laue diffractometer at the Australian Centre for Neutron Scattering (ANSTO, AU) at 5, 105 and 295 K. Single-crystal X-ray diffraction experiments were also performed using the XIPHOS I diffraction facility at the Newcastle University (UK), at the same temperatures. The two polymorphs, whose packing is explained by intermolecular interaction energies calculated using the Pixel method, show differences in the energy and geometry of the H-bond formed along the c-direction. Taking advantage of the X-ray diffraction data collected at 5 K, the precision and accuracy of the new Hirshfeld atom refinement method implemented in NoSpherA2 were probed choosing different settings of functionals and basis sets, along with the use of explicit clusters of molecules and enhanced rigid-body restraints. Equivalent atomic coordinates and anisotropic displacement parameters were compared and found to agree well with those obtained from the corresponding neutron structural models. Coupling single-crystal X-ray and neutron diffraction techniques provides the highest-quality structural information about a molecular solid in crystalline form. Nevertheless, X-ray and neutron diffraction data are usually collected using separate samples. This is a disadvantage when the material is studied at high pressure because it is very difficult to achieve exactly the same pressure in two separate experiments, especially if the neutron data are collected using Laue methods where precise absolute values of the unit-cell dimensions cannot be measured to check how close the pressures are. In Chapter 4, diffraction data have been collected under the same conditions on the same sample of copper(II) sulfate pentahydrate, using a conventional laboratory diffractometer and source for the X-ray measurements and the Koala diffractometer for the neutron measurements. The sample, of dimensions 0.40 -; 0.22 -; 0.20 mm3 and held at a pressure of 0.71 GPa, was contained in a miniature Merrill-Bassett diamond-anvil cell. The highly-penetrating diffracted neutron beams passing through the metal body of the miniature cell yielded data suitable for structure refinement, and compensated for the low completeness of the X-ray measurements, which was only 24% on account of the triclinic symmetry of the sample and the shading of reciprocal space by the cell. The two data sets were combined in a single 'X-N' structure refinement in which all atoms, including H-atoms, were refined with anisotropic displacement parameters. The precision of the structural parameters was improved by a factor of up to 50% in the X-N refinement compared to refinements using the X-ray or neutron data separately. Chapter 5 of the thesis is devoted to a new method for experimental determination of the change in internal energy as a function of pressure. This is accomplished using thermodynamic relationships between this quantity, the bulk modulus and the thermal expansion coefficient, which are accessible through pressure -volume - temperature equation of state (EoS) measurements. Rather few EoSs of small organic molecules are known. This lack of information is due to issues in performing the crystallographic experiment, since varying together pressure and temperature is quite a challenge for any diffractometer or beamline. The experimental challenges were addressed in this work by the use of the variable temperature insert for the Paris-Edinburgh press available on the PEARL instrument, at the ISIS Neutron and Muon spallation Source (UK), and by the Wombat high-intensity diffraction instrument at ANSTO. The method is demonstrated using hexamethylenetetramine, which has a relatively simple high-symmetry crystal structure. The variation of internal energy with pressure inferred from these results is compared with the results of periodic DFT calculations and of the Pixel method.