Structure elucidation

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Structure elucidation , also structural analysis or structural analysis , describes the elucidation of the composition of chemical compounds . Chemical substances can differ in terms of the spatial arrangement of the individual atoms in their molecules , even if their atomic composition is the same ( isomerism ). As a branch of analytical chemistry, structural analysis comprises chemical and physical methods to elucidate the chemical structure of substances.

Also, the structural chemistry , solid state chemistry , condensed matter physics and crystallography , as well as material testing and metallography concerned with the elucidation and description of structures, the spatial arrangement of atoms, molecules and ions in solids . In surface chemistry and physics , the structure of a surface is of particular importance, as special effects often arise at a phase transition.

Chemical methods

Some functional groups in organic molecules can be found with simple chemical detection reactions:

The individual results of these reactions are often not conclusive evidence because some of the samples are not entirely specific or fail in the presence of certain other functional groups. Usually only the combination of several test methods brings certainty about the structure of the examined connection.

Instrumental methods

"Small Molecules"

By elemental analysis the composition can, that is, the proportion of atoms of each element in a molecule , at a chemical compound determined. In the case of organic molecules, however, this is usually not enough to be able to draw a structural formula of the molecule. A number of spectroscopic methods are available to obtain additional information about the topology of the molecule .

This includes:

  • NMR : provides information about neighboring hydrogen atoms , relative distances between the hydrogen atoms in the molecule, as well as limited information about the linkage of the atoms through their chemical shift
  • Mass spectrometry : Shows the total mass of the molecule and, depending on the technology used, the mass of fragments into which a molecule breaks down during mass spectrometry.
  • Infrared spectroscopy : allows conclusions to be drawn about the existence of certain functional groups in the molecule
  • Single crystal X-ray structure analysis: leads to a three-dimensional model of all heavier atoms (hydrogen atoms are only shown very poorly)

In particular, it is often necessary to determine the stereochemistry of a newly synthesized chiral substance. Of the spectroscopic methods mentioned above, only X-ray structure analysis and, in some cases, NMR spectroscopy can be used for this task.

Before these techniques were known, only a relative stereochemistry could be determined by tracing back the as yet uncharacterized substance by means of chemical reactions to substances that had already been characterized. This was particularly important for the configuration of the sugars .

Biological macromolecules

Structure determination with X-ray diffraction

The structure elucidation of proteins and DNA today differs from that of small molecules because the primary structure , i.e. H. the linkage of the individual atoms is already known. The interest here is generally in the folding (also protein structure ), ie the exact spatial arrangement of the atoms in the molecule.

Of the techniques mentioned above, only X-ray structural analysis and NMR are used to elucidate the spatial structure of biomacromolecules .

For the X-ray structure analysis, it is necessary to obtain single crystals of the biomacromolecules of sufficient size. This is often only possible by means of many different crystallization attempts; often no crystals are obtained at all (for example because the protein has flexible areas). It can take months to years to preserve crystals. If the crystals are present, however, the corresponding structures can usually be obtained within days or weeks from the recorded diffraction patterns .

The structure elucidation by means of NMR analyzes the biomacromolecules directly in solution. There is therefore no need to fear that the structures obtained are falsified by the embedding in a crystal lattice and the additional forces acting on the molecule as a result. However, only atoms with a magnetic moment (an odd spin quantum number) of the atomic nucleus are accessible by NMR. In particular, this is hydrogen and 13 C and phosphorus 31 P (in DNA and RNA) which occur naturally in carbon to 1% in addition to 12 C. In order to be able to obtain more information, including about other types of atoms, molecules must be used in which isotopes suitable for NMR such as 13 C or 15 N have been enriched.

Analysis of two or three-dimensional NMR spectra can provide the following information about the substance:

Proteins

The structure elucidation is of interest in proteins, since the protein is only able to act as an enzyme in one of several possible folds .

DNA and RNA

The first structure determination of DNA goes back to X-ray structure determination by Rosalind Franklin . Their X-ray diffraction diagrams provided the essential information about the structure of DNA, which was published in 1953 by James Watson and Francis Crick.

The first high-resolution structure of a DNA duplex in the B conformation, the so-called Dickerson dodecamer , was discovered in 1981 by Drew , Dickerson et al. released. The coordinates of this dodecamer are available in the Brookhaven Protein Data Bank under the code 1BNA. It is regarded as a prototype for the structure of "normal" DNA in the B conformation and has since been refined in numerous other studies or used as a reference.

When determining the structure of DNA today, the type of attachment of DNA to a protein or an organic molecule (for example a drug) to the DNA is often of interest. This applies in particular to chemically modified DNA that is used in research and analysis . In addition, DNA can form triplexes , quatruplexes and hairpin structures .

The structural diversity of RNA is generally greater than that of DNA. This means that RNA forms complex structures to a greater extent than DNA, such as in t-RNA or snRNA .