X-ray crystallography is a landmark development in the structural study of a range of atoms and molecules which can be rendered in crystalline form. It was invented by the two William Braggs, father and son, in 1912, taking advantage of the discovery of X-ray diffraction in 1912.
The arrangement of these atoms or molecules is in large part responsible for their properties, which is why this field of study is so useful. Understanding this relationship drives the production of new molecules and materials which have customized physical and chemical properties such as novel enzyme cofactors based upon the visualization of existing ones.
Many areas of science such as chemistry, geology, biology and materials science depend upon this technique for a deeper understanding of the subject matter, whether this is a living cell, a liquid crystal, a quasicrystal, or a ceramic. Again, being able to visualize the precise fit between molecules which are interdependent for their function is a crucial part of scientific research today.
X-Ray crystallography scientific equipment used to resolve three-dimensional structure of biological molecules such as proteins and DNA. Image Credit: Gregory A. Pozhvanov / Shutterstock
This data can help scientists produce drugs or living particles which can be fitted to viruses or living cells to produce the desired effects simply by being designed to fit to the ligand molecule.
The principle is simple and is based on the finding that when X-rays are passed through a crystal a specific diffraction pattern is produced by the impact of the molecules on the path of the rays. This two-dimensional pattern is then interpreted with the help of mathematical programs as well as scientific and artistic skill and intuition to help understand the structure of the molecule which could have produced it.
The position of the dots helps to determine the arrangement of atoms and the bond lengths and angles within the molecule. X-rays are successful in achieving this because their wavelength (0.4–0.6 Å) is almost the same as the average interatomic distance.
The most challenging part of the whole process is growing impeccable crystals since in their absence good images cannot be obtained. The first substances to be studied were crystals such as quartz but today anything that can be obtained in the form of an orderly solid is grist to its mill.
An X-ray crystallography machine uses a four-circle diffractometer to rotate the crystal and the detector between the X-ray source and the screen, which receives the rays that have passed through the crystal.
The impact of the rays on the crystal forms a pattern of spots on the screen, called a diffraction pattern. The density of the spots varies with the amount of interference between the diffracted electrons at each point.
The diffraction pattern or electron density map is generated, reflecting the contour lines along which electron density is highest and so providing the location of atoms. This is transformed into a three-dimensional representation of the atomic or molecular structure using Fourier transformation, a complex mathematical procedure.
The best-known application of X-ray diffraction is probably the elucidation of the double-stranded helical structure of DNA by Rosalind Franklin, Francis Crick and James Watson in the 1950s. Other important molecules whose structures have been worked out include insulin, penicillin and vitamin B12.