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IUPAC International Chemical Identifier for Cholesterol

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IUPAC International Chemical Identifier for Cholesterol See also www.iupac.org/publications/ci/indexes/tools-of-the-trade.html Tools of the Trade requirements for nomenclature and other ways of The IUPAC designating chemical compounds. The need for a com- puterized equivalent of an IUPAC name (i.e., a standard International chemical identifier) was recognized, and after some exploratory studies, including a September 2000 Chemical Identifier: consultative meeting in Cambridge, UK, with repre- InChl—A New Standard for sentatives from a number of interested organizations, Molecular Informatics a project to develop such an identifier was launched early in 2001. The project is described in detail on the by Alan McNaught IUPAC website.1 The work on the Chemical Identifier was carried out he emergence of computerized information- under IUPAC auspices by Dmitrii Tchekhovskoi, Steve handling systems has had an enormous impact Stein, and Steve Heller at the US National Institute of Ton chemistry and chemists. The ease with which Standards and Technology (NIST). Their approach is chemical information can be shuttled around the world to express a chemical structure in terms of five lay- is phenomenal. Nevertheless, we are only just begin- ers of information (connectivity, tautomeric, isotopic, ning to exploit the huge potential of the computer stereochemical, and electronic). In the final representa- for sharing and processing such information. A major tion the unique connectivity layer is essential, but the stumbling block has been the lack of agreement on user can choose which other layers to keep. The InChI standard ways of structuring and encoding molecular algorithm converts input structural information into information (i.e., chemical structures and properties). the identifier in a three-step process: normalization (to Progress in this area has been disappointingly slow. remove redundant information), canonicalization (to Although work towards a standard format for chemical generate a unique set of atom labels), and serializa- structure files has been discussed extensively during tion (to give a string of characters). The procedure the past decade, it has been inhibited by various tech- generates a different Identifier for every compound, nical and political factors. However, the widespread but always gives the same identifier for a particular availability of the Internet and IUPAC’s increasing compound regardless of how the structure is input. interest in these problems have now helped create an Of course, the procedure is equally applicable to both environment where progress can be made. known and as yet unknown compounds. A PC-based, executable version of an InChI test There are many ways of specifying the identity of a algorithm was released in March 2002. This version chemical compound. Chemical identifiers can be infor- was developed to deal with well-defined, covalently- mation poor, carrying no information about molecular bonded organic molecules (both neutral and ionic). It structure (e.g., a registry number), or information was given to testers in a form that would accept struc- rich, allowing the structure to be deduced (e.g., a ture input in a commonly used format, and deliver data systematic name or a computerized representation of as tagged text. No problems were reported, and the bonding). Naming systems are internationally agreed InChI was received enthusiastically when presented (through IUPAC), but hitherto there has been no suc- at the Chemical Abstracts Service/IUPAC Conference cessful attempt to establish an agreed unique com- on Chemical Identifiers and XML for Chemistry, held puterized representation for any molecular structure. in Columbus, Ohio, USA, in July 2002. A further ver- There are several file formats in common use offering sion of the software, with applicability expanded to various approaches to uniqueness, but these are pro- deal with inorganic, organometallic, and coordination prietary, and generally geared to specific applications compounds, was presented at a meeting with poten- for their owners. Furthermore, as molecular structures tial users at NIST in November 2003. The meeting was of interest to researchers in chemistry become more intended to obtain further comments on desirable and more complex, our ability to devise nomenclature output formats, and in light of the feedback, version systems giving compact and intelligible names is being 1 of the InChI software was released in April 2005. An severely challenged. updated version was released in August 2006 (see An IUPAC strategy meeting in March 2000 at the IUPAC Wire, p. 23), along with a validation protocol National Academy of Sciences in Washington, D.C., for software developers to check the validity of output USA, brought together a broad spectrum of providers from applications incorporating the InChI algorithm. and users of chemical information to discuss future Figure 1 shows the InChI strings for two examples: 12 CHEMISTRY International November-December 2006 other InChI-related articles are listed on the IUPAC website.7 Anyone can easily obtain an InChI file at the desktop, or convert an InChI file back into a displayed structure. The availability of this new standard will enable a wide variety of applications, such as: O ordering chemicals from suppliers O finding compounds in the chemical/patent/gen- eral literature via text-based search engines O communication between databases O merging data collections developed using differ- ent systems/protocols O maintaining a laboratory chemical inventory or any broad-based local chemical collection O passing the “identity” of a substance to a col- league for use in any of the above Database providers have been among the first to recognize the enormous potential of InChI, and a list of these early adopters is provided on the IUPAC web- Figure 1. InChI strings for naphthalene and site.8 As a result, millions of identifiers are available [35Cl]chloro-L-glycinium. for searching on the web. At present, the largest col- the unsubstituted naphthalene molecule and the iso- lections are in the NIH/NCI database (~26 million), the topically substituted cation [35Cl]chloro-L-glycinium, NIH/PubChem database (~8 million), the Thomson/ISI with the component layers indicated. A full explana- database (~2 million), and the MDL/Elsevier database tion of the way in which layers are specified is given in (>2 million). The freely accessible PubChem database the InChI Technical Manual distributed with the InChI of the US National Institutes of Health9 also dem- software and on the InChI website at the University onstrates the utility of InChI in structure searching, of Cambridge (UK).2 The manual is an invaluable including both similarity and substructure searching10 source of answers to InChI-related questions. Figure 2 shows the software’s InChI display window, containing the structure, canoni- cal numbering, and identifier for cholesterol. For the International Chemical Identifier to fulfill its potential, software developers need to incor- porate it into their products. InChI files can already be generated easily by using the freely avail- able structure-drawing program ChemSketch,3 and the PubChem database of the US National Institutes of Health offers an online “InChI-generation-as-you- draw” facility.4 The Identifier has also been included as an integral component of Chemical Markup Language.5 The potential for using InChI in Internet searching is high- lighted in a recent article,6 and Figure 2. IUPAC International Chemical Identifier for cholesterol. CHEMISTRY International November-December 2006 13 Tools of the Trade and a similar facility is provided by the National Cancer information. This is especially difficult when chemistry Institute’s Chemical Structure Lookup Service, allowing researchers are confronted with data overload, an the use of InChIs to search 78 databases containing a increasingly common issue. Because of rapid advances total of ~31 million entries.11 in high-throughput chemistry and analysis, traditional Publishers of all varieties of chemical information approaches to the dissemination of data, or even the are recognizing the identifier as an essential way of wide range of chemical databases available now, can “labelling” molecular data. We will all reap the benefits not keep pace with the rate at which new data is gen- of a generally accepted convention for uniquely repre- erated. Therefore, it is proving ever more difficult to senting and communicating electronically the identity assess the validity of the information. of any chemical substance. The InChI provides an excellent way of calculating a unique computer-readable identifier from a structure References file, admittedly it is not an identifier that a person 1. www.iupac.org/projects/2000/2000-025-1-800.html would wish to employ, but we have IUPAC names for 2. http://wwmm.ch.cam.ac.uk/inchifaq that. It is even possible to use the InChI in a Google 3. www.acdlabs.com/products/chem_dsn_lab/chemsketch search to locate articles pertaining to specific mol- 4. http://pubchem.ncbi.nlm.nih.gov/edit ecules.3 5. www.xml-cml.org Increasingly, the value of depositing data along 6. "Enhancement of the Chemical Semantic Web through the with publications is understood as a way to promote Use of InChI Identifiers," Simon J Coles, Nick E Day, Peter Murray-Rust, Henry S Rzepa and Yong Zhang, Org. Biomol. its subsequent re-use and the information, supporting Chem., 2005, 3, 1832–1834. (doi: 10.1039/b502828k) the provenance and enabling re-analysis. Some of this 7. www.iupac.org/inchi/articles.html material can be stored as supplementary data at a jour- 8. www.iupac.org/inchi/adopters.html nal site, but this does not usually support a rich enough 9. http://pubchem.ncbi.nlm.nih.gov description to ensure that the data can be found and 10. http://pubchem.ncbi.nlm.nih.gov/search accessed in a digital form.4 The InChI works well in 11. http://cactus.nci.nih.gov/lookup providing a link to chemical information stored in a repository. At Southampton, we initially experimented Alan McNaught <[email protected]> has been involved with InChI since the beginning.
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