CRYSTALGROWER - A NEW APPROACH TO UNDERSTANDING AND PREDICTING CRYSTAL GROWTH

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The program of study for this AstraZeneca funded CASE studentship would involve applying the CrystalGrower methodology to problems of specific interest to the pharmaceuticals industry and AstraZeneca in particular. This will involve: i) experimental measurements of crystal surface topography using our Atomic Force Microscopy techniques which are specifically designed to observing micron-sized crystals under growth and dissolution conditions; ii) application of the CrystalGrower software to simulate crystal habit and surface topography to extract free energies crystallisation for fundamental growth processes iii) developments of the CrystalGrower computer software to address problems of specific interest. Part (iii) will include developments such as treating the nucleation of competing polymorphs but will also include "understanding and modelling why crystallisation sometimes fails to remove impurities" which is one of the targets identified in the AZ remit. This is not something that is included at present but would be an extension of the CrystalGrower approach to the effect of growth modifiers outlined in our Nature publication.The program of study will give the student a wide-ranging grounding in the science of crystallisation. This will include experimental methods of crystal production, all the basic characterisation of electron microscopy and x-ray diffraction. The student will become an expert in the use of in situ atomic force microscopy for the study of crystal growth and dissolution. The student will be encouraged to be involved in the development of the CrystalGrower software, developing coding skills. The student will utilise the CrystalGrower software, thereby obtaining a detailed nanoscopic view of the mechanism of crystal growth and how the experimental parameters may be altered to affect: crystal habit, crystal size, inclusion or otherwise of impurities; development of defects and intergrowths; competition between polymorphs.The timeliness of this studentship could not be more pertinent with the recent disclosure of this new methodology to approach crystal growth. We currently work together with partners in Curtin University, Australia (Julian Gale) on molecular dynamics and ab initio routes to understand crystal growth mechanistic pathways; Samara University, Russia (Vladislav Blatov) to produce mathematical crystal networks for the CrystalGrower input; STFC, Daresbury (Chris Morris) on super-computing facilities and code optimisation. The student would have interactions with all these world-class groups that will give an excellent grounding in all aspects of crystal growth simulation.The work will be publishable in the highest ranking journals such as Nature, Science, Journal of the American Chemical Society, Angewande Chemie etc.