Simplified molecular input line entry specification or smiles

The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of chemical molecules using short ASCII strings

• 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

SMILES

• Simplified Molecular Input Line Entry System (SMILES)

• Widely used AND computationally efficient

• Uses atomic symbols and a set of intuitive rules

• Uses hydrogen-suppressed molecular graphs (HSMG)

The term Canonical SMILES refers to the version of the SMILES specification that includes rules for ensuring that each distinct chemical molecule has a single unique SMILES representation

• The term Canonical SMILES refers to the version of the SMILES specification that includes rules for ensuring that each distinct chemical molecule has a single unique SMILES representation

• A common application of Canonical SMILES is for indexing and ensuring uniqueness of molecules in a database

• The term Isomeric SMILES refers to the version of the SMILES specification that includes extensions to support the specification of isotopes, chirality, and configuration about double bonds

• A notable feature of these rules is that they allow rigorous partial specification of chirality.

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

• 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

SMILES Bonds

• SINGLE*

• DOUBLE

• TRIPLE

• AROMATIC*

• * can be omitted

SMILES Branches

• Represented by enclosure in parentheses

• Can be nested or stacked

• Examples:

• CC(O)CC is 2-Butanol
• OCC(C)C is iso-Butanol
• OC(C)(C)C is tert-Butanol

SMILES Bonds

• Ethene

• Chloroethene

• 1,1-Dichloroethene

• cis-1,2-Dichloroethene

• Trichloroethene

• Perchloroethene

SMILES Symbols

• String of alphanumeric characters and certain punctuation symbols

• Terminates at the first space encountered when read left to right

• The ORGANIC SUBSET:

• B, C, N, O, P, S, F, Cl, Br, I

Other SMILES Atoms

• Aliphatic or nonaromatic carbon: C

• Atom in aromatic ring: lowercase letter

• Designate ring closure with pairs of matching digits, e.g.

• c1ccccc1 is Benzene, whereas
• C1CCCCC1 is Cyclohexane

SMILES Charges

• Specify attached hydrogens and charges in square brackets

• Number of attached hydrogens is the symbol H followed by optional digit

SMILES Charges

• [H+]

• [OH-]

• [OH3+]

• [Fe++]

• [NH4+]

SMILES Cyclic Structures

• Break one single or one aromatic bond in each ring

• Number in any order

• Designate ring-breaking atoms by the same digit following the atomic symbol

Cyclic Structures

• Numbers indicate start and stop of ring

• Same number indicates start and end of the ring, entered immediately following the start/end atoms

• Only numbers 1 – 9 are used

• A number should appear only twice

• Atom can be associated w. 2 consecutive numbers, e.g., Napthalene: c12ccccc1cccc2

SMILES Conventions

• Avoid two consecutive left parentheses if possible

• Strive for the fewest number of possible branches

• Tautomeric bonds are not designated; enter the appropriate form

Further Restrictions

• A branch cannot begin a SMILES notation

• A branch cannot immediately follow a double- or triple-bond symbol

• Example: C=(CC)C is invalid, but

• C(=CC)C or C(CC)=C are valid SMILES

SMILES Fragments

• Nitro

• Nitrate

• Nitrite

• Sulfonic acid

• Cyanide/Nitrile

• Azide

• Azido

Disconnected Structures

• Tetramethyl ammonium bromide

• C[N+]C(C)C.[Br-]

Isomeric and Chiral SMILES

• Isomeric configuration indicated by forward and backward slashes: / \

• Examples:

• trans-1,2-dibromoethene: Br/C=C/Br
• cis-1,2-dibromoethene: Br/C=C\Br

• Chirality indicated by the “@” symbol

Another Application

• SMILESCAS Database

• http://esc.syrres.com/interkow/smilecas.htm

• Over 103,000 SMILES notations

• Input CAS Registry Number

• Leads to SMILES and thence to a structure search