461649 Improving the Search for Polymorphs

Thursday, November 17, 2016: 12:35 PM
Cyril Magnin I (Parc 55 San Francisco)
Isaac Sugden, Imperial College, London, United Kingdom, Claire Adjiman, Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, London, United Kingdom, Costas Pantelides, Process Systems Enterprise, London, United Kingdom and Manolis Vasileiadis, Department of Chemical Engineering, Imperial College London,Center for Process Systems Engineering, London, United Kingdom

Improving the search for polymorphs.

I. Sugden, C.Gatsiou, M. Vasiliadis, C.S. Adjiman, and C.C. Pantelides

Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, SW7 2AZ, London, UK

The CrystalPredictor I1,2 and II3 codes used to explore the space of crystal structures have been used successfully in several crystal structure prediction (CSP) investigations in recent years4, including in the series of blind tests organised by the Cambridge Crystallographic Data Centre5,6 and in the prediction of the crystal structures of pharmaceutically-relevant molecules7,8. CSP methods can have an important role to play in the polymorph screening of pharmaceutically relevant molecules, by identifying potential low energy crystal structures.

We present a summary of CrystalPredictor, focussing on improvements to the lattice energy evaluation that the most recent blind test9, as well as our own investigations into a variety of flexible polymorphic molecules, has prompted. These improvements aim to achieve greater accuracy in the initial ranking of potential crystal structures, while managing computational cost so that a thorough exploration of the search space is possible. Firstly we discuss non-uniform LAMs; an innovation in CrystalPredictor II that allows the most efficient use of computational effort to cover a flexible molecule’s conformational space. We use blind test molecule 26 as an example.

Secondly, we discuss the smoothing of the intramolecular potential, which improves accuracy in CrystalPredictor II by collating data from ab initio calculations. The impact of this approach is investigated based on a CSP study for flufenamic acid10.

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(4) Pantelides, C. C.; Adjiman, C. S.; Kazantsev, A. V. Top Curr Chem 2014, 345, 25.

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(6) Bardwell, D. A.; Adjiman, C. S.; Arnautova, Y. A.; Bartashevich, E.; Boerrigter, S. X. M.; Braun, D. E.; Cruz-Cabeza, A. J.; Day, G. M.; Della Valle, R. G.; Desiraju, G. R.; van Eijck, B. P.; Facelli, J. C.; Ferraro, M. B.; Grillo, D.; Habgood, M.; Hofmann, D. W. M.; Hofmann, F.; Jose, K. V. J.; Karamertzanis, P. G.; Kazantsev, A. V.; Kendrick, J.; Kuleshova, L. N.; Leusen, F. J. J.; Maleev, A. V.; Misquitta, A. J.; Mohamed, S.; Needs, R. J.; Neumann, M. A.; Nikylov, D.; Orendt, A. M.; Pal, R.; Pantelides, C. C.; Pickard, C. J.; Price, L. S.; Price, S. L.; Scheraga, H. A.; van de Streek, J.; Thakur, T. S.; Tiwari, S.; Venuti, E.; Zhitkov, I. K. Acta Crystallogr B 2011, 67, 535.

(7) Vasileiadis, M.; Pantelides, C. C.; Adjiman, C. S. Chem Eng Sci 2015, 121, 60.

(8) Vasileiadis, M.; Kazantsev, A. V.; Karamertzanis, P. G.; Adjiman, C. S.; Pantelides, C. C. Acta Crystallographica Section B-Structural Science 2012, 68, 677.

(9) Reilly, A. M. e. a. Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials 2016.

(10) Lopez-Mejias, V.; Kampf, J. W.; Matzger, A. J. J Am Chem Soc 2012, 134, 9872.

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