Other SMILES Extensions

Some external programs may also need more information about exactly how many hydrogen atoms are attached to each heavy atom. The impsmiles function will produce a SMILES that contains the implicit hydrogen atom count. For example, impsmiles ( CC (C) 0 ) returns [CH3] [CH]([CH3])[OH], 

As discussed above, hydrogen atoms are handled differently from other atoms in SMILES and SMARTS. When searching for structures matching CC all structures will be found that contain ethane as a substructure. Of course, this does not mean [CH3][CH3], but rather any two single-bonded carbon atoms with any number of H atoms attached. One could be more specific and search for, say, [CH][CH] to require exactly one H atom on each carbon. 

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SMILES strings are very concise and hence are suitable for storing and transporting a large number of molecular structures, while MOLfiles and its extension SDFiles have the option to store more complicated molecular data such as 3D molecular conformational information and biological data associated with the molecules. There are many other file formats not discussed here. Interested readers can find a list of file types at the following web site http //www.ch.ic.ac.uk/chemime/. 

Extensive work by Smiles and his collaborators and by other groups clarified the main features of the rearrangement involving nitro-, sulfonyl- and halo-substituted aromatic rings. Rearrangement of 2-amino-pyridine derivatives has also been extensively studied. Reactions involved the replacement of hetero-substituents, a C - O bond by a C - N bond (N - 0), C - S by C - N (N - S) and C - S by C - O (O - S), etc. Early work has been reviewed by Bun-nett [3] (1951) and Truce [4] (1970). 

The external representation of molecular structure is a less rigorous definition. For example, there are many programs available that can convert to and from SMILES and molfiles. These can be used when a molfile (the external representation) needs to be imported as a SMILES (the internal representation) into the database. Similarly, a SMILES can be easily exported as a SMILES or converted to a molfile or other file format. It is useful to have these conversion functions as SQL extensions. 

Reaction SMILES is an extension to standard SMILES used to represent a specific reaction. It uses punctuation to distinguish reactants from products. For example, the reaction SMILES CC(=0)0.CN CC(=0)NC.0 represents the reaction of acetic acid with methylamine to form N-methylacetamide plus water. As with standard SMILES, explicit H atoms are typically not shown, although they may be. For example, the same reaction can represented as [CH3]C(=0)[0FI].[CH3][NH2] [CH3]C(=0)[NH][CH3].[H]0[H]. The punctuation is used to separate reactants from products, and the period is used to separate reactants or products from each other. There are no rules in reaction SMILES that enforce correct reaction stoichiometry or other aspects of actual chemical reactions. 

The Simplified Molecular Input Line Entry System (SMILES) is the most popular line notation in use today, and though it technically remains a proprietary product of Daylight Chemical Information Systems Inc., it has been widely implemented by other vendors. Unfortunately this has led to some divergence of dialects of the notation, especially with respect to extensions to... 

SMARTS is a language that allows specifying substructures using rules that are straightforward extensions of the SMILES language. In addition, there are several other extensions of the algorithm, e.g., searching for sequences of amino acids, and for chemical reactions, both for reactants and educts. 

It integrates name to stracture parsing using OPSIN [86] and ChEBI (Chemical Entities of Biological Interest) identifiers [87]. OPSIN converts an lUPAC name to SMILES or INChl to stmcture. OSCAR performs all the important tasks such as identifying chemical names, reaction name, and small compound and enzyme prefix, suffix, and adjectives. It comes with an extensive API for developing extensions with other tools such as Tavema [88] Mendeley [89] and U-Compare [90]. 

These simple rules allow very rapid encoding of most chemical structures and need only a few simple additions to cope with other atoms, charges, isomers, etc. Specification of atoms not in the organic subset, for example, is coded by use of an atomic symbol within square brackets. An extensive description of the SMILES system is given by Weininger and Weininger (1990). 

Inspired in the combination of the Ugi-Smiles reaction with other transformations, the same group envisaged a new route for the construction of indole scaffolds 121 based on an extension of this novel Ugi-Smiles protocol with a subsequent Heck cyclization in an one-pot procedure (Scheme 7.50) [107]. 

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