CHAPTER 5 CONCLUSION
2.2 Polymorphism
2.2.2 Characterization of polymorphs
2.2.2.1 Single Crystal X-ray Diffraction Analysis
Three-dimensional (3D) arrangements of atoms define the unique structures and properties of materials. For example, diamond and graphite both consist of only carbon atoms. The divergence in the 3D arrangement of carbon atoms caused diamond to have different structures and physicochemical properties from graphite (American, 2007). This signified that structure determination in material is vital since it contains useful information about the properties and characteristics of the compound. However, human eyes are unable to directly identify the structural arrangements of material due to the limitation in the
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resolution of wavelength but can obtain it through the X-ray crystallography method.
The history of X-ray crystallography can be traced back to the discovery of X-ray by Wilhelm Conrad Rontagen in 1895 (Hasegawa, 2012; Wilhelm Conrad Röntgen- Biographical, 2021). In 1912, Max von Laue introduced the concept of X-ray diffraction pattern during X-ray experiment with copper sulphate crystal (Hasegawa, 2012; Pumpo, 2016). One year later, being idealised by Max von Laue’s study, William Henry Bragg and William Lawrence Bragg discovered Bragg’s Law which describes the X-ray diffraction phenomena and makes the determination of the positions of atoms mathematically possible (Hasegawa, 2012). So far, there are two common types of X-ray diffraction methods (i.e. single crystal X-ray diffraction method and powder X-ray diffraction method) employed by researchers in the structural determination of material. For the powder X-ray diffraction method, it provides only one- dimensional information about the structure of the solid compound. It is useful when the target sample contains different structure from its parent sample and shows limitation when dealing with conformation polymorph that has identical crystal structure but different in arrangement. By contrast, single crystal X-ray diffraction method is a more complicated and time-consuming analysis since it interprets crystal data in three-dimensionality way. To date, the single crystal X-ray diffraction analysis still remains as the “golden standard” method used to elucidate and characterize the structure of material (Bond, 2016). It able to provide an absolute inside “look” of solid compounds at molecular level (Batsanov, 2010) where the powder X-ray diffraction unable to do it.
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Single crystal X-ray diffraction can provide detailed information about the crystalline solid compound including crystal space group, lattice parameters, atomic coordinates, types of atoms, bond distances, bond angles, dihedral angles, and hydrogen bond interactions. This geometry information is significantly important and acts as the main input data for computational calculation in Density Functional Theory. Besides, it also excels in the detection of disorder and defect in crystal compounds. For example, Sun et al. (2002) discovered two disorder sites with 50:50 occupancy at the methyl group of theophylline molecule during their single crystal X-ray diffraction study on theophylline monohydrate polymorph. Evidently, the single crystal X-ray diffraction method shows outstanding performances in the determination and identification of polymorphism phenomena in pharmaceutical drug compounds since it is sensitive than other analysis methods (i.e. powder X-ray diffraction, FT-IR, and UV-Vis) (Bunaciu et al., 2015). However, as the name suggested in single crystal X-ray diffraction technique, the target sample must be only in single crystal solid form. This caused the employment of single crystal X-ray diffraction analysis to be difficult since the formation of crystal with good quality and suitable size sometimes can be a tricky process.
The instrument used in the single crystal X-ray diffraction method is known as X-ray diffractometer. Figure 2.1 (a) shows the conceptual diagram of X-ray diffractometer taken from the paper written by Bond (2016). It consists of three basic components: X-ray source, goniometer, and X-ray detector (Bunaciu et al., 2015; Bond, 2016). When a voltage is applied, the heated tungsten filament in the cathode ray tube will produce electrons and accelerate toward the
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anode metal (i.e. Cu or Mo), resulting in the formation of X-ray source. The generated X-ray source will shoot the crystal sample and caused diffraction phenomena. This is the basic operation principle in X-ray diffraction techniques.
As the incident ray passes through the crystal sample satisfied the condition in Bragg’s Law, constructive interference will occur and a peak intensity of diffracted ray can be obtained (Bunaciu et al., 2015). Those diffraction patterns contain important details about the structural content of the crystal sample at the molecular level because each of the solid crystalline compounds has its own unique “fingerprint” diffraction pattern (Pinar, 2017). Equation 2.29 represents the formula of Bragg’s Law (Bunaciu et al., 2015).
𝜆 = 2𝑑𝑠𝑖𝑛𝜃
(Equation 2.29) The symbol 𝜆 is the wavelength of X-ray, 𝑑 represents the interplanar spacing that generating the diffraction and 𝜃 is the diffraction angle of X-ray. In additions, the goniometer in the X-ray diffractometer will simultaneously rotate the crystal sample and X-ray detector. This is to study and determine the diffraction patterns of the crystal sample in more detail multi-dimension areas where the Bragg’s law is satisfied and useful diffracted X-rays pattern can be obtained. For X-ray detector, it is rotating in 2𝜃 axis horizontally within the goniometer while the crystal sample is rotating under three types of axis (i.e. ω, ϕ, and χ). The ω-axis and χ-axis are about the horizontal and vertical rotation within the plane of the goniometer while the ϕ-axis is about the horizontal rotation on the mounting plane of the crystal sample. Figure 2.1 (b) illustrates the example of the diffraction pattern (dots structures) obtain from the technical article written by Hasegawa (2012). All the dots (diffracted rays) are detected, collected, and
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recorded by the X-ray detector with the help of a charge-coupled device (CCD).
The geometry position and intensity of the dots (diffracted rays) are important since they reveal the structural information (i.e. crystal orientation, lattice parameters, atoms types, and coordinates) of the crystal sample (Hasegawa, 2012; Pinar, 2017). Practically, the data collection process, rotation of goniometer, and interpretation of data are performed by researchers with the help of control software and data processing software with specific knowledge in the crystallography area in order to generate reliable output results.
Figure 2.1 (a): The single crystal X-ray diffractometer (Bond, 2016).
Figure 2.1 (b): The single crystal X-ray diffraction pattern (Hasegawa, 2012).
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