The International Chemical Identifier (InChI, pronounced IN-chee) is a textual identifier for chemical substances, designed to provide a standard way to encode molecular information and to facilitate the search for such information in databases and on the web. Initially developed by the International Union of Pure and Applied Chemistry (IUPAC) and National Institute of Standards and Technology (NIST) from 2000 to 2005, the format and algorithms are non-proprietary. Since May 2009, it has been developed by the InChI Trust, a nonprofit charity from the United Kingdom which works to implement and promote the use of InChI. The identifiers describe chemical substances in terms of layers of information — the atoms and their bond connectivity, tautomeric information, isotope information, stereochemistry, and electronic charge information. Not all layers have to be provided; for instance, the tautomer layer can be omitted if that type of information is not relevant to the particular application. The InChI algorithm converts input structural information into a unique InChI identifier in a three-step process: normalization (to remove redundant information), canonicalization (to generate a unique number label for each atom), and serialization (to give a string of characters). InChIs differ from the widely used CAS registry numbers in three respects: firstly, they are freely usable and non-proprietary; secondly, they can be computed from structural information and do not have to be assigned by some organization; and thirdly, most of the information in an InChI is human readable (with practice). InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names. They can express more information than the simpler SMILES notation and, in contrast to SMILES strings, every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI; for this purpose a format such as PDB can be used. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length (27 character) condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds, since these were problematic with the full-length InChI. Unlike the InChI, the InChIKey is not unique: though collisions are expected to be extremely rare, there are known collisions. InChI was first released in 2005. A major milestone was version 1.02 of January 2009, which provided a means to generate so called standard InChI, a version of the InChI with a fixed level of detail and collection of layers. The standard InChIKey is then the hashed version of the standard InChI string. The standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Since version 1.07.1 (August 2024), the software uses the MIT license, and may be downloaded from the InChI GitHub site. Beside the implementation in molecule editors, stand-alone executables have been packaged for multiple Linux distributions, including Debian.
Generation In order to avoid generating different InChIs for tautomeric structures, before generating the InChI, an input chemical structure is normalized to reduce it to its so-called core parent structure. This may involve changing bond orders, rearranging formal charges and possibly adding and removing protons. Different input structures may give the same result; for example, acetic acid and acetate would both give the same core parent structure, that of acetic acid. A core parent structure may be disconnected, consisting of more than one component, in which case the sublayers in the InChI usually consist of sublayers for each component, separated by semicolons (periods for the chemical formula sublayer). One way this can happen is that all metal atoms are disconnected during normalization; so, for example, the InChI for tetraethyllead will have five components, one for lead and four for the ethyl groups. The first, main, layer of the InChI refers to this core parent structure, giving its chemical formula, non-hydrogen connectivity without bond order (/c sublayer) and hydrogen connectivity (/h sublayer.) The /q portion of the charge layer gives its charge, and the /p portion of the charge layer tells how many protons (hydrogen ions) must be added to or removed from it to regenerate the original structure. If present, the stereochemical layer, with sublayers b, /t, /m and /s, gives stereochemical information, and the isotopic layer /i (which may contain sublayers /h, /b, /t, /m and /s) gives isotopic information. These are the only layers which can occur in a standard InChI. If the user wants to specify an exact tautomer, a fixed hydrogen layer /f can be appended, which may contain various additional sublayers; this cannot be done in standard InChI though, so different tautomers will have the same standard InChI (for example, alanine will give the same standard InChI whether input in a neutral or a zwitterionic form.) Finally, a nonstandard reconnected /r layer can be added, which effectively gives a new InChI generated without breaking bonds to metal atoms. This may contain various sublayers, including /f.
Format and layers
Every InChI starts with the string InChI= followed by the version number, currently 1. If the InChI is standard, this is followed by the letter S for standard InChIs, which is a fully standardized InChI flavor maintaining the same level of attention to structure details and the same conventions for drawing perception. The remaining information is structured as a sequence of layers and sub-layers, with each layer providing one specific type of information. The layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter (except for the chemical formula sub-layer of the main layer). The six layers with important sublayers are:
… excerpt ends here. Continue reading the full article.
