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Polymorphism in materials science is the ability of a solid material to exist in more than one form or crystal structure. Polymorphism can potentially be found in any crystalline material including polymers and metals and is related to allotropy which refers to elemental solids. Together with polymorphism the complete morphology of a material is described by other variables such as crystal habit, amorphous fraction or Crystallographic defects. Polymorphism is relevant to the fields of pharmaceuticals, agrochemicals, pigments, dyestuffs, foods and explosives.
When polymorphism exists as a result of difference in crystal packing it is called packing polymorphism. Polymorphism can also result from the existence of different conformers of the same molecule in conformational polymorphism. In pseudopolymorphism the different crystal types are the result of hydration or solvation. An example of an organic polymorph is glycine which is able to form monoclinic and hexagonal crystals.
An anologous phenomenon for amorphous materials is polyamorphism, when a substance can take on several different amorphous modifications.
Polymorphism in pharmaceuticals
Polymorphism is important in the development of pharmaceutical ingredients. Many drugs are regulatory approved based on a single crystal form or polymorph. In a classic patent case the pharmaceutical company GlaxoSmithKline defended its patent for the polymorph type II of the active ingredient in Zantac against competitors while that of the polymorph type I had already expired. Polymorphism in drugs can also have direct medical implications. Medicine is often administered orally as a crystalline solid and dissolution rates depend on the exact crystal form of a polymorph.
Despite the potential implications polymorphism is not always well understood. In 2006 a new crystal form was discovered of maleic acid 124 years after the first crystal structure determination . Maleic acid is a chemical manufactured on a very large scale in the chemical industry and is a salt forming component in medicine. The new crystal type is produced when a caffeine - maleic acid co-crystal (2:1) is dissolved in chloroform and when the solvent is allowed to evaporate slowly. Whereas form I has monoclinic space group P21/c, the new form has space group Pc. Both polymorphs consist of sheets of molecules connected through hydrogen bonding of the carboxylic acid groups but in form I the sheets alternate with respect of the net dipole moment whereas in form II the sheets are oriented in the same direction.
1,3,5-Trinitrobenzene is more than 125 years old and was used as an explosive before the arrival of the safer 1,3,5-trinitrotoluene. Only one crystal form of 1,3,5-trinitrobenzene has been known in the space group Pbca. In 2004, a second polymorph wss obtained in the space group Pca2(1) when the compound was crystallised in the presence of an additive, trisindane. This experiment shows that additives can induce the appearance of polymorphic forms.
Polymorphism is also established for acetylsalicylic acid . A new crystal type was found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile. Form II is only stable at 100 K and reverts back to from II at ambient temperature. In form I two salicyl molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds and in the newly discovered form II each salicyl molecule forms the same hydrogen bonds but then with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups both polymorphs form identical dimer structures.
Trivia
McCrone’s Law states that every compound has different polymorphic forms, and that, in general,the number of forms known for a given compound is proportional to the time and money spent in research on that compound.
Crystal Polymorphs can disappear. There have been cases of individual laboratories growing one crystal form. They then grow a different crystal form, and are unable to make the first form again. Alternatively, they find that they can make the first form again but it now converts to the second form over time. The drug Paroxetine was subject to a law suit that hinged on such a pair of polymorphs (A link to a discussion of cases in Canada and the US has been given below).
References
- Investigating the latent polymorphism of maleic acid Graeme M. Day, Andrew V. Trask, W. D. Samuel Motherwell and William Jones Chemical Communications, 2006, (1), 54 - 56 DOI: 10.1039/b513442k Abstract
- The Predictably Elusive Form II of Aspirin Peddy Vishweshwar, Jennifer A. McMahon, Mark Oliveira, Matthew L. Peterson, and Michael J. Zaworotko J. Am. Chem. Soc.; 2005; 127(48) pp 16802 - 16803; (Communication) DOI: 10.1021/ja056455b Abstract
External links
"Polymorphism (materials science)"