(136a) Accurate and Efficient Representation of Intramolecular Energy in Ab Initio Generation of Crystal Structures

Authors: 
Sugden, I. - Presenter, Imperial College
Adjiman, C. S., Imperial College London
Pantelides, C. C., Process Systems Enterprise Ltd.
Gatsiou, C. A., Imperial College London
The CrystalPredictor I1,2 and II3 codes have been used to explore the space of crystal structures 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.

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. We discuss the smoothing of the intramolecular potential in a Non-Uniform context10; 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, as well as short case studies on the polymorphic landscapes of Bromhexine HCl and Aripiprazole.

(1) Karamertzanis, P. G.; Pantelides, C. C. J Comput Chem 2005, 26, 304.

(2) Karamertzanis, P. G.; Pantelides, C. C. Mol Phys 2007, 105, 273.

(3) Habgood, M.; Sugden, I. J.; Kazantsev, A. V.; Adjiman, C. S.; Pantelides, C. C. J Chem Theory Comput 2015, 11, 1957.

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

(5) Day, G. M.; Cooper, T. G.; Cruz-Cabeza, A. J.; Hejczyk, K. E.; Ammon, H. L.; Boerrigter, S. X. M.; Tan, J. S.; Della Valle, R. G.; Venuti, E.; Jose, J.; Gadre, S. R.; Desiraju, G. R.; Thakur, T. S.; van Eijck, B. P.; Facelli, J. C.; Bazterra, V. E.; Ferraro, M. B.; Hofmann, D. W. M.; Neumann, M. A.; Leusen, F. J. J.; Kendrick, J.; Price, S. L.; Misquitta, A. J.; Karamertzanis, P. G.; Welch, G. W. A.; Scheraga, H. A.; Arnautova, Y. A.; Schmidt, M. U.; van de Streek, J.; Wolf, A. K.; Schweizer, B. Acta Crystallogr B 2009, 65, 107.

(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. et. al. Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials 2016.

(10) Sugden I, Adjiman CS, Pantelides CC Acta Crystallographica Section B-Structural Science 2016, 72, 864.