X-ray Birefringence Imaging and other fundamental aspects of solid organic inclusion compounds

This thesis presents new experimental techniques and utilizes these strategies in the analysis of solid organic inclusion compounds. This thesis also reports the production of a new series of co-crystals and examines their crystal structures. Chapter 1 acts as an introduction to the materials studied in this research. It explains the properties of inclusion compounds and lists the chemical materials used for these experiments. Chapter 2 explains the experimental techniques used in this research. Specifically it explains X-ray diffraction, X-ray birefringence and in-situ solid-state NMR. Chapter 3 presents a new technique for spatially resolved mapping of specific bond orientations in anisotropic solid materials using wide beam linearly polarized X-rays and an area detector. Earlier work with a focussed beam and a point detector showed the sensitivity of X-ray Birefringence to the orientation of specific energy-matching bonds inside a material, but these experiments only probed a small section of the crystal. Our wide beam imaging technique (X-ray Birefringence Imaging) shows similar sensitivity but allows us to investigate the full crystal simultaneously, which allows us to identify different domains within a single crystal. We apply this technique to a model material (1 bromocyclohexane/thiourea) which undergoes a low temperature phase transition and serves to demonstrate the usefulness of imaging techniques - in the high temperature phase the relevant C−Br bonds are isotropically disordered and no birefringence is observed, in the low temperature phase the relevant C−Br bonds are ordered but there are three possible orientations for the bromocyclohexane molecule so different regions of the crystal exhibit different birefringent signal. This behaviour is very clear on an imaging technique, but can appear highly confusing when using point-detector techniques. Chapter 4 utilizes X-ray Birefringence Imaging to investigate the dynamic rotational properties of guest molecules in a different set of solid organic inclusion compounds. By studying the known structures of 1,10-dibromodecane/urea and 1,8-dibromooctance/urea we have determined that XBI is a time-averaged and space-averaged technique. Additionally this chapter utilizes a Ge(555) analyzer instead of the Si(555) analyzer, which results in better spatial resolution and a different beam shape on the final images. Chapter 5 utilizes solid-state in-situ NMR to monitor crystallization processes as they occur and gain insight on competitive uptake of different guest molecules within the inclusion compound. These experiments use alkane and α,ω-dibromoalkane guest molecules inside urea inclusion compounds where the urea host structure (created in-situ) acts like a one-dimensional tunnel confining the guest. Every position within the urea tunnel is equivalent (a property of the incommensurate structure) which serves to simply the solid-state NMR spectra and means that for a given atom at the end of an alkane chain the only difference in NMR site comes from the neighbour molecule along the tunnel. This means in the solid phase we can observe peak splitting on certain atoms based on neighbour environment (e.g. the -CH3 in undecane will give a slightly different chemical shift if the neighbouring guest molecule is another undecane compared to if the neighbouring guest molecule is 1,8-dibromooctane) which in turn allows us to extract some information about the ordering within the inclusion compound. In these experiments we can also clearly distinguish between the same molecules in different phases, so as crystallization occurs we observe the loss of solution signal alongside the gain of solid signal. Additionally these experiments show no evidence of any intermediate structures or transition states. Chapter 6 describes a new set of organic co-crystals formed by reacting thiourea with α,ω-diiodoalkane chains and examines the crystal structures of these materials. Chapter 7 details further work and potential applications of this research. Digital data includes animated videos of the X-ray birefringence imaging data obtained in Chapter 3 and CIF files of the structures determined in Chapter 6

`NMR Crystallization': in-situ NMR techniques for time-resolved monitoring of crystallization processes

Solid-state NMR spectroscopy is a well-established and versatile technique for studying structural and dynamic properties of solids, and there is considerable potential to exploit the power and versatility of solid-state NMR for in-situ studies of chemical processes. However, a number of technical challenges are associated with adapting this technique for in-situ studies, depending on the process of interest. Recently, an in-situ solid-state NMR strategy for monitoring the evolution of crystallization processes has been developed and has proven to be a promising approach for identifying the sequence of distinct solid forms present as a function of time during crystallization from solution, and for the discovery of new polymorphs. The latest development of this technique, called “CLASSIC” NMR, allows simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time, thus yielding complementary information on the evolution of both the liquid phase and the solid phase during crystallization from solution. This article gives an overview of the range of NMR strategies that are currently available for in-situ studies of crystallization processes, with examples of applications that highlight the potential of these strategies to deepen our understanding of crystallization phenomena

Reactions in solid-state inclusion compounds

This chapter focuses on chemical reactions occurring within solid organic inclusion compounds, encompassing a broad range of inclusion compounds and a wide variety of different reaction types, including reactions of the guest molecules (such as dimerization, polymerization, cyclization, isomerization, and decomposition), reactions involving the host molecules, and guest exchange processes. In many cases, chemical transformations of guest molecules confined within solid host structures proceed with a high degree of selectivity toward a single product, and often with a high degree of stereoselectivity and/or enantioselectivity, as a consequence of the geometrical constraints imposed on the reacting molecules by the host structure. For this reason, the products obtained from such reactions are often significantly different from those obtained from the corresponding reactions in the solution state or in the “pure” crystalline phase of the guest molecules. Through the examples highlighted in this chapter, general issues relating to reactions in solid organic inclusion compounds are rationalized and discussed

New in situ solid-state NMR techniques for probing the evolution of crystallization processes: pre-nucleation, nucleation and growth

The application of in-situ techniques for investigating crystallization processes promises to yield significant new insights into fundamental aspects of crystallization science. With this motivation, we recently developed a new in-situ solid-state NMR technique that exploits the ability of NMR to selectively detect the solid phase in heterogeneous solid/liquid systems (of the type that exist during crystallization from solution), with the liquid phase “invisible” to the measurement. As a consequence, the technique allows the first solid particles produced during crystallization to be observed and identified, and allows the evolution of different solid phases (e.g., polymorphs) present during the crystallization process to be monitored as a function of time. This in-situ solid-state NMR strategy has been demonstrated to be a powerful approach for establishing the sequence of solid phases produced during crystallization and for the discovery of new polymorphs. The most recent advance of the in-situ NMR methodology has been the development of a strategy (named “CLASSIC NMR”) that allows both solid-state NMR and liquid-state NMR spectra to be measured (essentially simultaneously) during the crystallization process, yielding information on the complementary changes that occur in both the solid and liquid phases as a function of time. In this article, we present new results that highlight the application of our in situ NMR techniques to successfully unravel different aspects of crystallization processes, focusing on: (i) the application of a CLASSIC NMR approach to monitor competitive inclusion processes in solid urea inclusion compounds, (ii) exploiting liquid-state NMR to gain insights into co-crystal formation between benzoic acid and pentafluorobenzoic acid, and (iii) applications of in-situ solid-state NMR for the discovery of new solid forms of trimethylphosphine oxide and L-phenylalanine. Finally, the article discusses a number of important fundamental issues relating to practical aspects, the interpretation of results and the future scope of these techniques, including: (i) an assessment of the smallest size of solid particle that can be detected in in-situ solid-state NMR studies of crystallization, (ii) an appraisal of whether the rapid sample spinning required by the NMR measurement technique may actually influence or perturb the crystallization behaviour, and (iii) a discussion of factors that influence the sensitivity and time-resolution of in-situ solid-state NMR experiments

Theoretical analysis of the background intensity distribution in X-ray Birefringence Imaging using synchrotron bending-magnet radiation

In the recently developed technique of X-ray Birefringence Imaging, molecular orientational order in anisotropic materials is studied by exploiting the birefringence of linearly polarized X-rays with energy close to an absorption edge of an element in the material. In the experimental setup, a vertically deflecting high-resolution double-crystal monochromator is used upstream from the sample to select the appropriate photon energy, and a horizontally deflecting X-ray polarization analyzer, consisting of a perfect single crystal with a Bragg reflection at Bragg angle of approximately 45°, is placed downstream from the sample to measure the resulting rotation of the X-ray polarization. However, if the experiment is performed on a synchrotron bending-magnet beamline, then the elliptical polarization of the X-rays out of the electron orbit plane affects the shape of the output beam. Also, because the monochromator introduces a correlation between vertical position and photon energy to the X-ray beam, the polarization analyzer does not select the entire beam, but instead selects a diagonal stripe, the slope of which depends on the Bragg angles of the monochromator and the polarization analyzer. In the present work, the final background intensity distribution is calculated analytically because the phase space sampling methods normally used in ray traces are too inefficient for this setup. X-ray Birefringence Imaging data measured at the Diamond Light Source beamline B16 agree well with the theory developed here

X-ray birefringence imaging

The polarizing optical microscope has been used since the 19th century to study the structural anisotropy of materials, based on the phenomenon of optical birefringence. In contrast, the phenomenon of x-ray birefringence has been demonstrated only recently and has been shown to be a sensitive probe of the orientational properties of individual molecules and/or bonds in anisotropic solids. Here, we report a technique—x-ray birefringence imaging (XBI)—that enables spatially resolved mapping of x-ray birefringence of materials, representing the x-ray analog of the polarizing optical microscope. Our results demonstrate the utility and potential of XBI as a sensitive technique for imaging the local orientational properties of anisotropic materials, including characterization of changes in molecular orientational ordering associated with solid-state phase transitions and identification of the size, spatial distribution, and temperature dependence of domain structures

Novel technique for spatially resolved imaging of molecular bond orientations using x-ray birefringence

Birefringence has been observed in anisotropic materials transmitting linearly polarized X-ray beams tuned close to an absorption edge of a specific element in the material. Synchrotron bending magnets provide X-ray beams of sufficiently high brightness and cross section for spatially resolved measurements of birefringence. The recently developed X-ray Birefringence Imaging (XBI) technique has been successfully applied for the first time using the versatile test beamline B16 at Diamond Light Source. Orientational distributions of the C–Br bonds of brominated “guest” molecules within crystalline “host” tunnel structures (in thiourea or urea inclusion compounds) have been studied using linearly polarized incident X-rays near the Br K-edge. Imaging of domain structures, changes in C–Br bond orientations associated with order-disorder phase transitions, and the effects of dynamic averaging of C–Br bond orientations have been demonstrated. The XBI setup uses a vertically deflecting high-resolution double-crystal monochromator upstream from the sample and a horizontally deflecting single-crystal polarization analyzer downstream, with a Bragg angle as close as possible to 45°. In this way, the ellipticity and rotation angle of the polarization of the beam transmitted through the sample is measured as in polarizing optical microscopy. The theoretical instrumental background calculated from the elliptical polarization of the bending-magnet X-rays, the imperfect polarization discrimination of the analyzer, and the correlation between vertical position and photon energy introduced by the monochromator agrees well with experimental observations. The background is calculated analytically because the region of X-ray phase space selected by this setup is sampled inefficiently by standard methods

Theoretical analysis of the background intensity distribution in X-ray Birefringence Imaging using synchrotron bending-magnet radiation

In the recently developed technique of X-ray Birefringence Imaging, molecular orientational order in anisotropic materials is studied by exploiting the birefringence of linearly polarized X-rays with energy close to an absorption edge of an element in the material. In the experimental setup, a vertically deflecting high-resolution double-crystal monochromator is used upstream from the sample to select the appropriate photon energy, and a horizontally deflecting X-ray polarization analyzer, consisting of a perfect single crystal with a Bragg reflection at Bragg angle of approximately 45°, is placed downstream from the sample to measure the resulting rotation of the X-ray polarization. However, if the experiment is performed on a synchrotron bending-magnet beamline, then the elliptical polarization of the X-rays out of the electron orbit plane affects the shape of the output beam. Also, because the monochromator introduces a correlation between vertical position and photon energy to the X-ray beam, the polarization analyzer does not select the entire beam, but instead selects a diagonal stripe, the slope of which depends on the Bragg angles of the monochromator and the polarization analyzer. In the present work, the final background intensity distribution is calculated analytically because the phase space sampling methods normally used in ray traces are too inefficient for this setup. X-ray Birefringence Imaging data measured at the Diamond Light Source beamline B16 agree well with the theory developed here

X-ray birefringence: a new strategy for determining molecular orientation in materials

While the phenomenon of birefringence is well-established in the case of visible radiation and is exploited in many fields (e.g., through the use of the polarizing optical microscope), the analogous phenomenon for X-rays has been a virtually neglected topic. Here, we demonstrate the scope and potential for exploiting X-ray birefringence to determine the orientational properties of specific types of bonds in solids. Specifically, orientational characteristics of C–Br bonds in the bromocyclohexane/thiourea inclusion compound are elucidated from X-ray birefringence measurements at energies close to the bromine K-edge, revealing inter alia the changes in the orientational distribution of the C–Br bonds associated with a low-temperature order–disorder phase transition. From fitting a theoretical model to the experimental data, reliable quantitative information on the orientational properties of the C–Br bonds is determined. The experimental strategy reported here represents the basis of a new approach for gaining insights into the orientational properties of molecules in anisotropic materials

X‑ray Birefringence Imaging of Materials with Anisotropic Molecular Dynamics

The X-ray birefringence imaging (XBI) technique, reported very recently, is a sensitive tool for spatially resolved mapping of the local orientational properties of anisotropic materials. In this paper, we report the first XBI measurements on materials that undergo anisotropic molecular dynamics. Using incident linearly polarized X-rays with energy close to the Br K-edge, the X-ray birefringence is dictated by the orientational properties of the C–Br bonds in the material. We focus on two materials (urea inclusion compounds containing 1,8-dibromooctane and 1,10-dibromodecane guest molecules) for which the reorientational dynamics of the brominated guest molecules (and hence the reorientational dynamics of the C–Br bonds) are already well characterized by other experimental techniques. The XBI results demonstrate clearly that, for the anisotropic molecular dynamics in these materials, the effective X-ray optic axis for the X-ray birefringence phenomenon is the <i>time-averaged</i> resultant of the orientational distribution of the C–Br bonds