Professor Kenneth Harris Project Titles
1. Advancing New Computational Techniques for Structure Determination using Powder X-ray Diffraction Data
Determination of crystal structures from single-crystal X-ray diffraction data is the most powerful tool for elucidating structural information in chemistry, and many of the most important scientific advances in the 20th Century relied on the use of this technique. However, the requirement for a single-crystal specimen imposes a limitation on the scope of this technique, as many materials of interest cannot be prepared as single crystals of sufficient size and quality, but instead can be prepared only as microcrystalline powders. To progress towards understanding the structural properties of such materials, the most direct route is to use powder X-ray diffraction data. However, solving crystal structures directly from powder X-ray diffraction data is associated with major difficulties, particularly for low-symmetry molecular solids, originating from the fact that there is extensive overlap of peaks in the powder X-ray diffraction pattern. In view of the fact that many important materials are microcrystalline powders, the development of new and increasingly powerful procedures for determining crystal structures directly from powder X-ray diffraction data has the potential to make considerable impact across several scientific disciplines. For these reasons, much of our current research is focused on developing and applying new methodologies for solving crystal structures from powder X-ray diffraction data. This work has led to the development of new "direct-space" techniques for structure solution, in which trial crystal structures are generated and explored using Monte Carlo or Genetic Algorithm search techniques. The PhD project will involve wide-ranging fundamental investigations to optimize the ways of implementing and applying the Genetic Algorithm technique, including the development of new evolutionary strategies. New approaches in which information on the energies of trial structures is incorporated within our consideration of the powder X-ray diffraction data will also be explored.
2. New Structural Insights on Biological Materials by Powder X-ray Diffraction Techniques
The on-going fundamental developments in our techniques for carrying out structure determination directly from powder X-ray diffraction data (as discussed in Project 1 above) are enabling these techniques to be exploited to solve structural problems of increasing complexity. In this regard, we are currently increasing our interest in applying these techniques to tackle structural problems of biological importance. In recent years, we have applied our techniques to determine a number of peptide structures that were selected primarily to address specific structural issues rather than to resolve important biological questions. Key target molecules for addressing biologically important questions are typically of greater complexity than the peptides studied so far, and pose correspondingly greater challenges for structure determination. In particular, the greatest challenges in direct-space structure solution from powder X-ray diffraction data arise for molecules with significant conformational flexibility, but our on-going methodological developments are improving considerably the capability of achieving successful structure solution in such cases. A number of realistic biological targets have been identified, based on peptide sequences that have direct implications for answering specific biological questions (but which cannot be prepared as single crystals suitable for single-crystal X-ray diffraction). The PhD project (which will involve collaborative research with groups from Chemical Biology and Biosciences at Cardiff University) will target the structure determination, from powder X-ray diffraction data, of peptides that are known to be implicated in specific biological problems.
3. Understanding Fundamentals of Crystallization Processes by In-Situ NMR and Other Techniques
There is currently considerable interest in developing improved strategies for controlling crystallization processes, not only from the viewpoint of advancing fundamental physico-chemical understanding, but also motivated by the importance of controlling the polymorphic form of crystalline materials produced in industrial applications. Crystallization processes are generally governed by kinetic factors, and meta-stable polymorphs are often produced instead of the thermodynamically stable polymorph. Furthermore, crystallization processes often evolve through a sequence of different polymorphic forms. With the aim of achieving the goal of being able to control crystallization processes such that the outcome (e.g. the polymorphic form of the product) can be predicted and controlled in a reliable and reproducible manner, an essential requirement is to understand the evolution of polymorphic forms produced as a function of time during a crystallization experiment. Much of our recent research has focused on understanding fundamental aspects of crystallization processes, including the development of a new solid-state NMR strategy for exploring the early stages of crystal growth processes and for identifying the solid phase present as a function of time during such processes. The PhD project will focus on applying this solid-state NMR strategy to gain new insights on a number of specific questions relating to crystallization of molecular materials from solution, particularly motivated by mapping and understanding the evolution of different polymorphic forms (and inter-conversions between them) during crystallization processes.
4. Exploiting Solid-State Inclusion Phenomena in Materials Applications
Our previous research to develop a fundamental understanding of structural and dynamic properties of solid inclusion compounds was focused on organic framework structures (particularly urea and thiourea inclusion compounds) and demonstrated that these solids exhibit many interesting structural and dynamic aspects, such as incommensurate structural properties, order-disorder phase transitions, several different types of dynamic disorder, chiral recognition, etc. We are now initiating new directions of research aimed at exploiting this fundamental understanding in order to explore and develop applied aspects of these materials. The specific areas of interest for this PhD project are focused on: (i) developing, optimizing and applying general methods for controlling the crystal morphology (i.e. crystal shape) of tunnel inclusion compounds, (ii) understanding fundamentals and developing applications of exchange processes of guest molecules in organic tunnel structures, and exploring the behaviour of these materials as "molecular capillaries", and (iii) designing and developing solid inclusion compounds as new materials for applications in X-ray polarimetry (the new materials to be developed in this project have wide-ranging applications in many different areas of science, including X-ray astronomy).
5. Molecular Motion in Organic Materials using Solid-State NMR Techniques
There is a tendency to regard crystalline solids as rigid assemblies of atoms or molecules, devoid of the interesting molecular motions that occur for the same atoms or molecules when the solid is transformed into the molten or gaseous state. However, this picture is far from reality. The molecules and atoms in a crystalline solid are not motionless, and in many cases significant dynamic processes can occur. To fully understand the dynamics of a solid requires a range of experimental and computational techniques, with each technique able to probe the dynamic properties on a different characteristic timescale. The range of techniques employed in this area of our research includes solid-state NMR spectroscopy (particularly 2H NMR), incoherent quasielastic neutron scattering and molecular dynamics simulation techniques. As an illustration of the complementarity of these techniques, 2H NMR spectroscopy is sensitive to motions occurring at rates in the range 103 s–1 to 108 s–1, whereas incoherent quasielastic neutron scattering and molecular dynamics simulation are sensitive to faster motions, occurring at rates greater than about 1010 s–1. To fully characterize the dynamic properties of a solid generally requires a combination of these techniques to be applied. The PhD project will explore a variety of dynamic processes in solids using a combination of these techniques, focused in three main areas: (i) dynamics of hydrogen-bonding arrangements in solids, (ii) dynamics of guest molecules included within host solids, and (iii) dynamics of water molecules in crystalline hydrates.