Crystal polymorphism
"[4] Additionally, Walter McCrone described the phases in polymorphic matter as "different in crystal structure but identical in the liquid or vapor states."
McCrone also defines a polymorph as “a crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state.”[5][6] These defining facts imply that polymorphism involves changes in physical properties but cannot include chemical change.
The studies involved measuring the interfacial angles of the crystals to show that chemically identical salts could have two different forms.
[9] The development of the microscope enhanced observations of polymorphism and aided Moritz Ludwig Frankenheim’s studies in the 1830s.
He was able to demonstrate methods to induce crystal phase changes and formally summarized his findings on the nature of polymorphism.
Soon after, the more sophisticated polarized light microscope came into use, and it provided better visualization of crystalline phases allowing crystallographers to distinguish between different polymorphs.
This invention helped crystallographers determine melting points and observe polymorphic transitions.
[8] While the use of hot stage microscopes continued throughout the 1900s, thermal methods also became commonly used to observe the heat flow that occurs during phase changes such as melting and polymorphic transitions.
One such technique, differential scanning calorimetry (DSC), continues to be used for determining the enthalpy of polymorphic transitions.
[8] Vibrational spectroscopic methods came into use for investigating polymorphism in the second half of the twentieth century and have become more commonly used as optical, computer, and semiconductor technologies improved.
Mid-frequency IR and Raman spectroscopies are sensitive to changes in hydrogen bonding patterns.
Additionally, terahertz and low frequency Raman spectroscopies reveal vibrational modes resulting from intermolecular interactions in crystalline solids.
[10] The combination of techniques provides detailed information about crystal structures, similar to what can be achieved with x-ray crystallography.
This technique uses computational chemistry to model the formation of crystals and predict the existence of specific polymorphs of a compound before they have been observed experimentally by scientists.
The new crystal type is produced when a co-crystal of caffeine and maleic acid (2:1) is dissolved in chloroform and when the solvent is allowed to evaporate slowly.
Diamond, and londsdaleite are chemically identical, both having sp3 hybridized bonding, and they differ only in their crystal structures, making them polymorphs.
[24] Polymorphism in binary metal oxides has attracted much attention because these materials are of significant economic value.
[25] [26] A classical example of polymorphism is the pair of minerals calcite, which is rhombohedral, and aragonite, which is orthorhombic.
The concept hinges on the idea that unstable polymorphs more closely resemble the state in solution, and thus are kinetically advantaged.
[27] Nevertheless, there are known systems, such as metacetamol, where only narrow cooling rate favors obtaining metastable form II.
Polymorphic purity of drug samples can be checked using techniques such as powder X-ray diffraction, IR/Raman spectroscopy, and utilizing the differences in their optical properties in some cases.
[11] Dibenzoxazepines Multidisciplinary studies involving experimental and computational approaches were applied to pharmaceutical molecules to facilitate the comparison of their solid-state structures.
A combined experimental and computational study demonstrated that the methyl group in loxapine has a significant influence in increasing the range of accessible solid forms and favouring various alternate packing arrangements.
CSP studies have again helped in explaining the observed solid-state diversity of loxapine and amoxapine.
The combination of experimental and computational approaches has provided a deeper understanding of the factors influencing the solid-state structure and diversity in these compounds.
[11] Form II was reported in 2005,[47][48] found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile.
[50] Cortisone acetate exists in at least five different polymorphs, four of which are unstable in water and change to a stable form.
[32][34] Polytypes are a special case of polymorphs, where multiple close-packed crystal structures differ in one dimension only.
[55] Another example is tantalum disulfide, where the common 1T as well as 2H polytypes occur, but also more complex 'mixed coordination' types such as 4Hb and 6R, where the trigonal prismatic and the octahedral geometry layers are mixed.
[57] It has been suggested that this type of polymorphism is due to kinetics where screw dislocations rapidly reproduce partly disordered sequences in a periodic fashion.
