A new kind of aspirin confirmed….
This is a little bit of an article based on a paper I coauthored a little while ago.
Aspirin (acetylsalicylic acid) has been around for over 100 years. By the 1960s there was some suspicion that a second polymorph of aspirin might exist. A polymorph, in this context, is a crystal structure type. When crystals of aspirin are grown by dissolving powder in some solvent usually the crystals form a particular crystal structure — known as form I. But if the crystallisation conditions are changed, by changing temperatures, solvents, concentrations and so on, it may be possible to push the aspirin molecules into combining in a slightly different arrangement, so that a different crystal structure arises. This would then be a second polymorph of aspirin. This second polymorph was finally found as recently as 20051, and its structure elucidated soon after2.
But there was some uncertainty — is form II a real polymorph, or is it conventional aspirin (form I) with lots of interruptions to the crystal structure?
We studied crystals of the two forms of aspirin, and measured the X-ray scattering from them using the Advanced Photon Source at the Argonne National Laboratory in Chicago3 and also at the Australian Synchrotron in Melbourne (http://www.synchrotron.org.au/). We can get amazingly detailed patterns formed by X-rays diffracting off the crystals. For example4:
Modelling these patterns is difficult — and Eric Chan did a brilliant job of it. What he was able to show was that form II seems to be a real polymorph, but that it is extremely difficult to make it grow without it showing ‘errors’ in the stacking of the molecules (‘defects’). And these defects tend to look like tiny little regions of form I embedded in the form II, hence the question over whether form II was really a dodgy version of form I.
So it looks like there really is a new(ish) kind of aspirin.
Diffuse scattering data for aspirin form (I) were collected on the 11-ID-B beamline at the Advanced Photon Source, Argonne, IL, USA. Diffuse scattering data for aspirin form (II) were collected on the powder diffraction beamline at the Australian Synchrotron, Victoria, Australia. The support of the Australian Research Council, the Australian Synchrotron Research Program and the NCI National Facility at the ANU is gratefully acknowledged. DJG gratefully acknowledges support of the Australian Institute of Nuclear Science and Engineering. We would also like to thank Dr Peter Chupas and Dr Karena Chapman of the Advanced Photon Source3, and Dr Kia Wallwork from the powder diffraction beamline of the Australian Synchrotron for assistance with the collection of the diffuse scattering data.
1. Vishweshwar, P., McMahon, J., Oliveira, M., Peterson, M. L. & Zaworotko, M. J. (2005). J. Am. Chem. Soc. 127, 16802–16803.
2. Bond, A. D., Boese, R. & Desiraju, G. R. (2007a). Angew. Chem. Int. Ed. 46, 615–617; Bond, A. D., Boese, R. & Desiraju, G. R. (2007b). Angew. Chem. Int. Ed. 46, 618–622.
3. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.
4. Chan, E. J., Welberry, T. R., Heerdegen, A. P. & Goossens, D. J. (2010). Acta Cryst. B66, 696-707. DOI: 10.1107/S0108768110037055