History of Polymorphism in Chemistry

X-ray Crystallography

• X-ray crystallography is commonly used to study the crystal structure of polymorphs.
• Both single crystal x-ray diffraction and powder x-ray diffraction techniques are used to obtain measurements of the crystal unit cell.
• Each polymorph of a compound has a unique crystal structure, resulting in different x-ray diffraction patterns.

Vibrational Spectroscopic Methods

• Vibrational spectroscopic methods, such as infrared (IR) spectroscopy, terahertz spectroscopy, and Raman spectroscopy, are used to investigate polymorphism.
• Mid-frequency IR and Raman spectroscopies are sensitive to changes in hydrogen bonding patterns.
• Terahertz and low frequency Raman spectroscopies reveal vibrational modes resulting from intermolecular interactions in crystalline solids.

Computational Methods

• Computational chemistry is used in combination with vibrational spectroscopy techniques to understand the origins of vibrations within crystals.
• The combination of techniques provides detailed information about crystal structures, similar to what can be achieved with x-ray crystallography.
• Crystal structure prediction is a technique that uses computational chemistry to model the formation of crystals and predict the existence of specific polymorphs of a compound.

Early Records of Polymorphism

• Eilhard Mitscerlich and Jöns Jacob Berzelius are credited for their studies of phosphates and arsenates in the early 1800s.
• They measured the interfacial angles of the crystals to show that chemically identical salts could have two different forms.
• Mitscerlich originally called this discovery isomorphism.

Historical Development of Polymorphism Studies

• Wilhelm Ostwald used the measurement of crystal density to study polymorphism and expressed it in Ostwald's Ratio.
• Moritz Ludwig Frankenheim demonstrated methods to induce crystal phase changes and formally summarized his findings on the nature of polymorphism.
• The development of the microscope, particularly the polarized light microscope, enhanced observations of polymorphism.
• Otto Lehmann invented the hot stage and fitted it to a polarized light microscope, allowing crystallographers to determine melting points and observe polymorphic transitions.

Thermal Methods

• Thermal methods, such as differential scanning calorimetry (DSC), are used to observe the heat flow that occurs during phase changes such as melting and polymorphic transitions.
• DSC is used to determine the enthalpy of polymorphic transitions.