Chemical structural information

In 1986, David Weininger created the SMILES Simplified Molecular Input Line Entry System) notation at the US Environmental Research Laboratory, USEPA, Duluth, MN, for chemical data processing. The chemical structure information is highly compressed and simplified in this notation. The flexible, easy to learn language describes chemical structures as a line notation [20, 21]. The SMILES language has found widespread distribution as a universal chemical nomenclature... 

Another approach applies graph theory. The analogy between a structure diagram and a topological graph is the basis for the development of graph theoretical algorithms to process chemical structure information [33-35]. 

The different internal and external file formats make it necessary to have programs which convert one format into another. One of the first conversion programs for chemical structure information was Babel (around 1992). It supports almost 50 data formats for input and output of chemical structure information [61]. CLIFF is another file format converter based on the CACTVS technology and which supports nearly the same number of file formats [29]. In contrast to Babel, the program is more comprehensive it is able to convert chemical reaction information, and can calculate missing atom coordinates [29]. 

Table 2-5. The most important File formats for exchange of chemical structure information.

To code the configuration of a molecule various methods are described in Section 2.8. In particular, the use of wedge symbols clearly demonstrates the value added if stereodescriptors are included in the chemical structure information. The inclusion of stereochemical information gives a more realistic view of the actual spatial arrangement of the atoms of the molecule imder consideration, and can therefore be regarded as between the 2D (topological) and the 3D representation of a chemical structure. 

Tabic 2-6 gives an overview on the most common file formats for chemical structure information and their respective possibilities of representing or coding the constitution, the configuration, i.c., the stereochemistry, and the 3D structure or conformation (see also Sections 2..3 and 2.4). Except for the Z-matrix, all the other file formats in Table 2-6 which are able to code 3D structure information arc using Cartesian coordinates to represent a compound in 3D space. 

J.M. Barnard, C.J. Jochum, S.M. Wel-ford, ROSDAL A universal structure/ substmcture representation for PC-host communication, in Chemical Structure Information Systems Interfaces Communication and Standards, WA. Warr (Ed.), ACS Symposium Series No. 400, American Chemical Sodety, Washington, DC, 1989, pp. 76- 81. 

In contrast to IR and NMR spectroscopy, the principle of mass spectrometry (MS) is based on decomposition and reactions of organic molecules on theii way from the ion source to the detector. Consequently, structure-MS correlation is basically a matter of relating reactions to the signals in a mass spectrum. The chemical structure information contained in mass spectra is difficult to extract because of the complicated relationships between MS data and chemical structures. The aim of spectra evaluation can be either the identification of a compound or the interpretation of spectral data in order to elucidate the chemical structure [78-80],... 

The previous discussion has centered on how to obtain as much molecular mass and chemical structure information as possible from a given sample. However, there are many uses of mass spectrometry where precise isotope ratios are needed and total molecular mass information is unimportant. For accurate measurement of isotope ratio, the sample can be vaporized and then directed into a plasma torch. The sample can be a gas or a solution that is vaporized to form an aerosol, or it can be a solid that is vaporized to an aerosol by laser ablation. Whatever method is used to vaporize the sample, it is then swept into the flame of a plasma torch. Operating at temperatures of about 5000 K and containing large numbers of gas ions and electrons, the plasma completely fragments all substances into ionized atoms within a few milliseconds. The ionized atoms are then passed into a mass analyzer for measurement of their atomic mass and abundance of isotopes. Even intractable substances such as glass, ceramics, rock, and bone can be examined directly by this technique. 

Since detailed chemical structure information is not usually required from isotope ratio measurements, it is possible to vaporize samples by simply pyrolyzing them. For this purpose, the sample can be placed on a tungsten, rhenium, or platinum wire and heated strongly in vacuum by passing an electric current through the wire. This is thermal or surface ionization (TI). Alternatively, a small electric furnace can be used when removal of solvent from a dilute solution is desirable before vaporization of residual solute. Again, a wide variety of mass analyzers can be used to measure m/z values of atomic ions and their relative abundances. 

As one of the indispensable software tools, the compound registration system provides a mechanism for the medicinal chemist to capture chemical structure information as well as analytical and other data in a database. We mention two of the systems below. 

Chemical structural information is one of the missing pieces in the great effort to bring biomedical research into the realm of twenty-first century information extraction and knowledge discovery paradigms. Proteins, genes, diseases, and chemical compounds constitute the major entities extracted in the biomedical domain. The ability to read structure information and substructure information and their association to other entities could have a major impact on toxicity information in particular and ADMET data in general. 

Varmuza, K. in Lindon, J. C., Tranter, G. E., Holmes, J. L. (Ed.), Encyclopedia of Spectroscopy and Spectrometry, Academic Press, London, United Kingdom, 2000, pp. 232-243. Chemical structure information from mass spectrometry. 

Toxicologists have begun to understand how the chemical structure and some of the other properties of these chemicals contribute to their carcinogenicity. One important part of the effort to reduce reliance upon animal testing involves further validation of the use of chemical structure information along with other properties of a chemical - its... 

Brown and others [12] describe the Merck, Sharp, and Dohme chemical structure information system which utilizes this approach. 

Eakin [13] describes the chemical structure information system at Imperial Chemical Industries Ltd., where registration is based on Wiswesser Line Notation. For connection tables, the unique, unambiguous representation is derived automatically, i.e., a single, invariant numbering of the connection table is algorithmically derived. 

A variety of algorithms for the computer handling of chemical structure information have been described. The techniques for... 

Lynch, Michael F., Judith M. Harrison, William G. Town, and Janet E. Ash, Computer Handling of Chemical Structure Information, American Elseview Publishing Company, Inc., New York, N.Y., 1971. 

Brown, H. D., Marianne Costlow, Frank A. Cutler, Albert N. DeMott, Walter B. Gall, David P. Jacobus, and Charles J. Miller, "The Computer-Based Chemical Structure Information System of Merck, Sharp and Dohme Research Laboratories," Journal of Chemical Information and Computer Sciences, 16(1), 5-10 (1976). 

Figure 15.6. Example of 13C chemical shift assignments of structural groups found in NOM. The asterisk marks the C atom which is found in the corresponding chemical shift region. Reprinted from Keeler, C., Kelly, E. F., and Maciel, G. E. (2006). Chemical-structural information from solid-state C-13 NMR studies of a suite of humic materials from a lower montane forest soil, Colorado, USA. Geoderma 130,124-140, with permission from Elsevier.

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