Daylight provides enterprise-level cheminformatics software technologies to life science companies. Our superior chemistry, high performance, and open architecture have earned Daylight a reputation for delivering the state-of-the-art in chemical information processing since 1987.
Daylight Chemical Information Systems, Inc. is a privately held company with corporate offices in Aliso Viejo, CA and research offices in Santa Fe, NM and Cambridge, England.
What is SMILES?
SMILES
Simplified Molecular Input Line Entry System
SMILESTM as a simple yet comprehensive chemical language in which molecules and reactions can be specified using ASCII characters representing atom and bond symbols. SMILESTM contains the same information as is found in an extended connection table but with several advantages. A SMILESTM string is human understandable, very compact, and if canonicalized represents a unique string that can be used as a universal identifier for a specific chemical structure. In addition, a chemically correct and comprehensible depiction can be made from any SMILESTM string symbolizing either a molecule or reaction.
SMILESTM development was initiated by David Weininger in the late 1980s using the concept of a graph with nodes as atoms and edges as bonds to represent a molecule. Parentheses are used to indicate branching points and numeric labels designate ring connection points. The basic SMILESTM grammar also includes as well as isotopic information, configuration about double bonds, and chirality leading to what is known as isomeric SMILESTM.
Acknowledgments
Development of SMILES was initiated by the author, David Weininger, at the Environmental Research Laboratory, U.S.E.P.A., Duluth, MN; the design was completed at Pomona College in Claremont, CA. It was embodied in the Daylight Toolkit with the assistance of Cedar River Software. IntroductionSMILES (Simplified Molecular Input Line Entry System) is a line notation (a typographical method using printable characters) for entering and representing molecules and reactions. Some examples are:
SMILES contains the same information as might be found in an extended connection table. The primary reason SMILES is more useful than a connection table is that it is a linguistic construct, rather than a computer data structure. SMILES is a true language, albeit with a simple vocabulary (atom and bond symbols) and only a few grammar rules. SMILES representations of structure can in turn be used as "words" in the vocabulary of other languages designed for storage of chemical information (information about chemicals) and chemical intelligence (information about chemistry).
Part of the power of SMILES is that unique SMILES exist. With standard SMILES, the name of a molecule is synonymous with its structure; with unique SMILES, the name is universal. Anyone in the world who uses unique SMILES to name a molecule will choose the exact same name.
One other important property of SMILES is that it is quite compact compared to most other methods of representing structure. A typical SMILES will take 50% to 70% less space than an equivalent connection table, even binary connection tables. For example, a database of 23,137 structures, with an average of 20 atoms per structure, uses only 1.6 bytes per atom when represented with SMILES. In addition, ordinary compression of SMILES is extremely effective. The same database cited above was reduced to 27% of its original size by Ziv-Lempel compression (i.e. 0.42 bytes per atom).
These properties open many doors to the chemical information programmer. Examples of uses for SMILES are:
- Keys for database access
- Mechanism for researchers to exchange chemical information
- Entry system for chemical data
- Part of languages for artificial intelligence or expert systems in chemistry
Branches
Branches are specified by enclosing them in parentheses, and can be nested or stacked. In all cases, the implicit connection to a parenthesized expression (a "branch") is to the left. Examples are:Cyclic Structures
Cyclic structures are represented by breaking one bond in each ring. The bonds are numbered in any order, designating ring opening (or ring closure) bonds by a digit immediately following the atomic symbol at each ring closure. This leaves a connected non-cyclic graph which is written as a non-cyclic structure using the three rules described above. Cyclohexane is a typical example:
Isomeric SMILES
This section describes the SMILES rules used to specify isotopism, configuration about double bonds, and chirality. The term isomeric SMILES collectively refers to SMILES written using these rules. The SMILES isomer specification rules allow chirality to be completely specified for any structure, if it is known. Unlike most existing chemical nomenclatures such as CIP and IUPAC, these rules are also designed to allow rigorous partial specification of chirality. Aside from use in macros, substructure searching, and other pattern matching operations, this is important because much of the world's available chemical information is known for structures with incompletely resolved chiralities (not all possible chiral centers are separated, known, or reported).All isomer specification rules in SMILES are therefore optional. The absence of a specification for any attribute implies that the value of that attribute is unspecified.
Aromaticity
Aromaticity must be deduced in a system such as SMILES which generates an unambiguous chemical nomenclature because of the fundamental requirement to characterize the symmetry of a molecule. Given effective aromaticity-detection algorithms, it is not necessary to enter any structure as aromatic if the user prefers to enter an aliphatic (Kekulé-like) structure. Entering structures as aromatic directly (i.e., by using lower case atomic symbols) provides a shortcut to accurate chemical specification and is closer to the mental molecular model used by most chemists. The SMILES algorithm uses an extended version of Hueckel's rule to identify aromatic molecules and ions. To qualify as aromatic, all atoms in the ring must be sp2 hybridized and the number of available "excess" p-electrons must satisfy Hueckel's 4N+2 criterion. As an example, benzene is written c1ccccc1, but an entry of C1=CC=CC=C1 - cyclohexatriene, the Kekulé form - leads to detection of aromaticity and results in an internal structural conversion to aromatic representation. Conversely, entries of c1ccc1 and c1ccccccc1 will produce the correct anti-aromatic structures for cyclobutadiene and cyclooctatetraene, C1=CC=C1 and C1=CC=CC=CC=C1. In such cases the SMILES system looks for a structure that preserves the implied sp2 hybridization, the implied hydrogen count, and the specified formal charge, if any. Some inputs, however, may not only be incorrect but also impossible, such as c1cccc1. Here c1cccc1 cannot be converted to C1=CCC=C1 since one of the carbon atoms would be sp3 with two attached hydrogens. In such a structure alternating single and double bond assignments cannot be made. The SMILES system will flag this as an "impossible" input. Please note that only atoms on the following list can be considered aromatic: C, N, O, P, S, As, Se, and * (wildcard). In addition, exocyclic double bonds do not break aromaticity.
Hydrogens
Hydrogens in reactions are handled as with molecules; they are suppressed unless "special". Recall that for molecules, hydrogens are special if they are: charged, isotopic, bonded to another hydrogen, or multiply bonded. With reactions, there is an additional case which will make a hydrogen special. It is often desirable (eg. 1,5-hydride shift) to store information about the location of hydrogens as part of the atom map of a reaction. Hydrogens with a supplied atom map are considered "special" and these hydrogens are not suppressed. These mapped hydrogens appear explicitly in Absolute SMILES for reactions. Otherwise, atom-mapped hydrogens do not appear in Unique SMILES.For More Information on SMILES, visit
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