Polymorphism @ Durham
The phenomenon of polymorphism (the ability of a material to crystallise in more than one solid form) is of critical importance in the fine chemicals sector, particularly for pharmaceutical industry where it has major regulatory and intellectual property implications. The differences between solid forms are rarely quite as visible as the case illustrated of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (nicknamed ROY), and so the characterisation of polymorphic behaviour, and understanding how it can be controlled, requires significant expertise and specialist equipment.
With its combination of staff and state-of-the-art equipment, the Durham Chemistry department is ideally placed to tackle issues of polymorph characterisation and control. This pages summarises our research interests and expertise in this area. Please contact us through the links below if you are interested in polymorphism issues either as a subject of postgraduate reseach or as a commercial/research problem. See also links to the right to our relevant analytical services in X-ray diffraction and Solid-State NMR.
Dr Paul Hodgkinson (Solid-State NMR)
Solid-state NMR is an invaluable complement to diffraction-based methods for polymorphism studies as it probes the local chemical environment, allowing solid forms to be easily distinguished, even when the crystallite sizes are too small to give Bragg diffraction. Disordered / amorphous and crystalline forms can be readily distinguished and quantitated, and there are few real limitations on sample form: mixtures and dynamic materials such as gels are all readily handled. Problems such as locating H atoms and establishing protonation states are easily addressed.
The Durham Solid-State NMR research group has state-of-the-art equipment, based around a dedicated 500 MHz spectrometer, including the latest generation of ultra-fast magic-angle spinning NMR probes. We have a long track record of collaboration with pharmaceutical companies both in developing research projects of common interest, and in providing solid-state NMR services (spectra, interpretation and bespoke training). Current relevant research interests include characterising structure and dynamics in pharmameutical solvates and the use of quantum chemical tools (DFT-based first principles calculation and Molecular Dynamics simulation) to connect link NMR measurements with diffraction studies ("NMR crystallography").
- Application Note 1: Molecular Organic Solids (pdf) (last modified: 17 January 2008)
Professor Jonathan W. Steed (Molecular Materials Chemistry)
The molecular materials group led by Professor Steed has extensive experience in research on crystalline molecular solids, X-ray and neutron crystallography and supramolecular chemistry. The group studies the self-assembly and application of small molecule gels, novel pharmaceutical solid forms, pharmaceutical hydrates and gel phase crystal growth methodologies. The group are experts in solid state characterisation techniques (Single crystal and powder diffraction, DSC, IR, melting point determination etc.) and their application to problems in polymorphism, co-crystals and low symmetry molecular structures (see www.dur.ac.uk/zprime for a web resource dedicated to this class of compound).
Professor John S. O. Evans (X-ray Powder Diffraction)
The XRPD facilities haeded by Prof. John Evans have state-of-the-art powder diffraction facilities which are ideally suited for the study of polymorphism. The suite includes three Bruker D8 powder diffractometers capable of measuring samples from 11 to 1500 K in both reflection and transmission geometry and under a range of conditions (variety of inert and reactive gases, vacuum, variable humidity, etc). The grouping has significant expertise and experience in most aspects of powder diffraction methods from qualitative and quantitative analysis to structure solution and refinement. More details about the facility are described in the link on the right.
Dr Sharon Cooper (Controlled Crystallisation)
Dr Sharon Cooper leads a group with expertise on the use of controlled crystallisation strategies to provide crystalline products with well-defined size, morphology and polymorphic form. Crystallisation from the confined volumes of emulsions and microemulsions are used to obtain a wide range of crystalline materials under ambient conditions. These include pharmaceuticals, inorganic nanocrystals and macromolecules. The ability to obtain thermodynamic control of crystallisation in microemulsions, so that the most stable polymorph of a drug can be found, is of particular importance. Small and wide angle X-ray scattering (SAXS and WAXS), laser light scattering, FTIR, ESEM, TEM and optical microscopy techniques are used to follow the crystallisation process and characterise the products.
Dr Ivana Evans (Functional Organic Materials)
Dr Ivana Evans is the leader of a group with expertise in polymorphism across the chemical spectrum, from functional inorganic oxides to small-molecule organics. In particular, the work on functional organic materials focusses on systems where dynamics of protons in strong hydrogen bonds induces polymorphism, phase transitions, or imparts specific physical properties (such as ferroelectricity).
This work relies on a number of experimental and computational techniques, including synthesis (solid state, solvothermal, crystal growth), crystallographic characterisation (powder and single crystal X-ray and neutron diffraction, in-situ non-ambient diffraction) and computational modelling (ab initio molecular dynamics).