Abstract

Molecular solids formed from the same molecule but with different crystalline arrangements are called polymorphic, whilst similar molecules with a minimal crystal structure change are termed isostructural, or isomorphic. In recent times, there is much interest in both cases and the two concepts intersect when considering whether molecular analogues of pharmaceutical compounds (APIs) will crystallise in identical, similar or entirely different manner.

Recently we described the structures of two potent anti-biotic compounds from bacterial sources, Albofungin and Chloroabofungin.1 These have a trivial point substitution of a single atom, which yield two different unit cells and packing in space groups P21 or C2.

The structures have i) similar molecular conformation ii) a similar 1D translational stack with pi-pi interactions and iii) form a similar  association with another molecular stack through several hydrogen bonds.  These associate with other pair stacks in different manner either through another 21 screw or via a 2-fold rotation, giving rise to the two 3D arrangements, which may be described as 2D isostructural with each other.  

In this poster we will explore other cases where molecular or molecular pair analogues have been crystallized and give what may be described as 0D, 1D, 2D or 3D isostructurality.  This evaluation can be made using the concept of Gelbrich and Hursthouse called the ‘Supramolecular Construct’ or SC.2 We show how this is useful in comparing and categorizing structural similarities and differences. Ultimately, we are interested to see whether molecular analogues with different structural arrangements can serve as hetero-templating seeds that can structure direct a particular crystallization, for APIs this could give rise to polymorphic forms with potential commercial implications.  At least in some cases, we and others have shown this to be the case. This includes new forms of carbamazepine3, arylsulphonyl derivatives of 11-azaartemisinin (11-Aza) 4 as well as cocrystals of 11-Aza with substituted salicylic acids.5,6 The polymorphs will be compared using the SC concept.

References:

1. W. Ye, W. She, H.H-Y Sung, P.Y. Qian, I.D. Williams Acta Cryst. (2020) C76, 1100-7.
2. T. Gelbrich, M.B. Hursthouse, CrystEngComm, (2005), 7, 324–336.
3. D.H. Case, V.K Srirambhatla, R. Guo, R.E. Watson, L.S. Price, H. Polyzois, J.K. Cockcroft, A.J. Florence, D.A.Tocher, S.L. Price, Cryst. Growth Des. (2018), 18, 5322-5331.
4. M. Nisar, H.H-Y. Sung, I,D. Williams, Acta Cryst (2018) A74, a104.
5. M. Roy, K. Li, M. Nisar, L.W-Y. Wong, H.H-Y. Sung, R.K. Haynes, I.D. Williams Acta Cryst. (2021) C77, 262-270
6. K. Li, M. Roy, M. Nisar, L.W-Y. Wong, H.H-Y. Sung, R.K. Haynes, I.D. Williams Crystals (2022) in press