Simplified molecular input line entry specification
The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules.
The original SMILES specification was developed by Arthur Weininger and David Weininger in the late 1980s. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems Inc. In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community.  Other 'linear' notations include the Wiswesser Line Notation (WLN), ROSDAL and SLN (Tripos Inc).
In August of 2006, the IUPAC introduced the InChI as a standard for formula representation.  SMILES is generally considered to have the advantage of being slightly more human-readable than InChI; it also has a wide base of software support with extensive theoretical (e.g., graph theory) backing.

# Terminology
The term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However the term SMILES is also commonly used to refer to both a single SMILES string and a number of SMILES strings and the exact meaning is usually apparent from the context. The terms Canonical and Isomeric can lead to some confusion when applied to SMILES.  The terms describe different attributes of SMILES strings and are not mutually exclusive.
Typically, a number of equally valid SMILES can be written for a molecule.  For example, CCO, OCC and C(O)C all specify the structure of ethanol. Algorithms have been developed to ensure the same SMILES is generated for a molecule regardless of the order of atoms in the structure.  This SMILES is unique for each structure, although dependent on the canonicalisation algorithm used to generate it, and is termed the Canonical SMILES.  These algorithms first convert the SMILES to an internal representation of the molecular structure and do not simply manipulate strings as is sometimes thought.  Algorithms for generating Canonical SMILES have been developed at Daylight Chemical Information Systems, OpenEye Scientific Software and Chemical Computing Group. A common application of Canonical SMILES is for indexing and ensuring uniqueness of molecules in a database.
SMILES notation allows the specification of configuration at tetrahedral centers, and double bond geometry.  These are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed Isomeric SMILES.  A notable feature of these rules is that they allow rigorous partial specification of chirality.  The term Isomeric SMILES is also applied to SMILES in which isotopes are specified.

# Graph-based definition
In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph. The chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree.

# Examples

## Atoms
Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as  for gold. The hydroxide anion is . Brackets can be omitted for the "organic subset" of B, C, N, O, P, S, F, Cl, Br, and I.  All other elements must be enclosed in brackets.  If the brackets are omitted, the proper number of implicit hydrogen atoms is assumed; for instance the SMILES for water is simply O.

## Bonds
Bonds between aliphatic atoms are assumed to be single unless specified otherwise and are implied by adjacency in the SMILES. For example the SMILES for ethanol can be written as CCO. Ring closure labels are used to indicate connectivity between non-adjacent atoms in the SMILES, which for cyclohexane and dioxane can be written as C1CCCCC1 and O1CCOCC1 respectively.  Double and triple bonds are represented by the symbols '=' and '#' respectively as illustrated by the SMILES O=C=O  (carbon dioxide) and C#N (hydrogen cyanide).

## Branching
Branches are described with parentheses, as in CCC(=O)O for propionic acid and C(F)(F)F for fluoroform.  Substituted rings can be written with the branching point in the ring as illustrated by the SMILES COc(c1)cccc1C#N (see depiction) and COc(cc1)ccc1C#N (see depiction) which encode the 3 and 4-cyanoanisole isomers.  Writing SMILES for substituted rings in this way can make them more human-readable.

## Aromaticity
Aromatic C, O, S and N atoms are shown in their lower case 'c', 'o', 's' and 'n' respectively.  Benzene, pyridine and furan can be represented respectively by the SMILES c1ccccc1, n1ccccc1 and o1cccc1. Bonds between aromatic atoms are, by default, aromatic although these can be specified explicitly using the ':' symbol. Aromatic atoms can be singly bonded to each other and biphenyl can be represented by c1ccccc1-c2ccccc2.  Aromatic nitrogen bonded to hydrogen, as found in pyrrole must be represented as  and imidazole is written in SMILES notation as n1ccc1.
The Daylight and OpenEye algorithms for generating canonical SMILES differ in their treatment of aromaticity.

## Stereochemistry
Configuration around double bonds is specified using the characters "/" and "\". For example, F/C=C/F (see depiction)is one representation of trans-difluoroethene, in which the fluorine atoms are on opposite sides of the double bond, whereas F/C=C\F (see depiction) is one possible representation of cis-difluoroethene, in which the Fs are on the same side of the double bond, as shown in the figure.
Configuration at tetrahedral carbon is specified by @ or @@.  L-Alanine, the more common enantiomer of the amino acid alanine can be written as NC(=O)O (see depiction).  The @@ specifier indicates that, when viewed from nitrogen along the bond to the chiral center, the  sequence of substituents hydrogen (H), methyl (C) and carboxylate (C(=O)O)appear clockwise.  D-Alanine can be written as NC(=O)O (see depiction).  The order of the substituents in the SMILES string is very important and D-alanine can also be encoded as  NO)C (see depiction).

## Isotopes
Isotopes are specified with a number equal to the integer isotopic mass preceding the atomic symbol.  Benzene in which one atom is carbon-14 is written as 1ccccc1 and deuterochloroform is C(Cl)(Cl)Cl.

## Other examples of SMILES
The SMILES notation is described extensively in the SMILES theory manual provided by Daylight Chemical Information Systems and a number of illustrative examples are presented. Daylight's depict utility provides users with the means to check their own examples of SMILES and is a valuable educational tool.

# Extensions
SMARTS is a line notation for specification of substructural patterns in molecules.  While it uses many of the same symbols as SMILES, it also allows specification of wildcard atoms and bonds, which can be used to define substructural queries for chemical database searching. One common misconception is that SMARTS-based subtructural searching involves matching of SMILES and SMARTS strings. In fact, both SMILES and SMARTS strings are first converted to internal graph representations which are  searched for subgraph isomorphism.  SMIRKS is a line notation for specifying reaction transforms.

# Conversion
SMILES can be converted back to 2-dimensional representations using Structure Diagram Generation algorithms (Helson, 1999). This conversion is not always unambiguous. Conversion to 3-dimensional representation is achieved by energy minimization approaches. There are many downloadable and web-based conversion utilities.