Daylight Summer School 2001, June 5-7, Santa Fe, NM

Reaction SMILES and SMIRKS

Reaction SMILES

Just as a SMILES represents a molecule, a reaction SMILES represents the molecules in a chemical reaction.

Daylight system is designed to be able to represent and store both completely specified reactions (graph-like reactions) and information-deficient reactions in a repeatable and searchable fashion.
Only pure structural information is stored in a lexical representation of the reaction
Additional data is not stored as part of the reaction but rather stored separately in the database. (e.g. stoichiometry, equilibrium constants, yield, conditions)
Daylight system is oriented towards single-step reactions

Reaction SMILES consist of potentially three parts each separated by a ">":

Reactant: A starting material. It is expected to participate in the reaction by contributing one or more atoms to the products.
Agent: Agents are molecules which do not contribute atoms to the product, or accept atoms from the reactants. Agents are commonly used for catalysts, solvents and other adjunts which are indirect participants.
Product: Molecules which are the final result of the reaction. All atoms in the product should come from the reactants.

Example


CC(=O)O.OCC>[H+].[Cl-].OCC>CC(=O)OCC

Atom Mapping

Reaction processing occurs by the use of Atom Maps. The atom map tells the computer which atoms are the same on the reactant and products sides of the reaction.

The map is always the last part of the atom expression delimited by a colon
Values are numbers without intrinsic meaning
Optional
If a hydrogen is mapped, it is also "special" and must be shown (Hydrogens are normally omitted from SMILES)

Example

[CH2:1]=[CH:2][CH:3]=[CH:4][CH2:5][H:6]>> [H:6][CH2:1][CH:2]=[CH:3][CH:4]=[CH2:5]

Searching Reactions

Extend SMARTS with '>' operator, like SMILES, with optional atom map.
Any valid Reaction SMILES is a valid SMARTS query.
Any valid Molecule SMARTS can be a component of a Reaction
Recursive SMARTS supports only molecule expressions.
All valid SMIRKS are valid reaction queries

Examples

CC(=O)[OH]>>CC(=O)OCC
Matches any reaction with a reactant acid and a product ester. Includes all esterification reactions, plus any reaction which happens to have the appropriate functionality in its components.
C[C:2](=[O:1])[OH:1]>>C[C:2](=[O:1])OCC
Matches esterification reactions.
(C[C:2](=O)[OH].[OH:3]C)>>C[C:2](=O)[O:3]C
Matches any intra-molecular esterification reaction.

(C[C:2](=O)[OH]).([OH:3]C)>>C[C:2](=O)[O:3]C

Matches any inter-molecular esterification reaction.

Example Reaction SMARTS:
Query:	Reaction:	Matches:
`C>>`	`CC>>CN`	2
`>C>`	`CC>>CN`	0
`>>C`	`CC>>CN`	1
`C`	`CC>>CN`	3

Transforms

A transform is a generic reaction defined in the Daylight world by a SMIRKS. SMIRKS is a hybrid language of SMILES and SMARTS which meets the requirements of reaction expressions:

Expression of a reaction graph
Expression of indirect effects

The SMIRKS rules are as follows:

Atoms can be added or deleted during a transformation
Atomic SMARTS expressions can be used for atoms directly involved in the reaction (the reaction center)
Stoichiometry is defined to be 1-1 for all atoms in the reactant and product for a transformation.
Explicit hydrogens that are used on one side of a transformation must appear explicitly on the other side of the transformation must be mapped.
Bond expressions must be valid SMILES (no bond queries allowed)
Atomic expressions may be any valid atomic SMARTS expression for nodes where the bonding (connectivity & bond order) doesn't change.

Examples
1. Nitro group conversion
  
  [*:1][N:2](=[O:3])=[O:4]>>[*:1][N+:2](=[O:3])[O-:4]
2. Enumeration of a combinatorial library - aminothiazole transformation
  
  [N:1][C:2](=[S:3])[NH2:4]([H:99])[H:100].[Cl,Br:5] [C:6]([H:101])[C:7]=[O:8]>> [s:3]1[c:2]([N:1])[n:4][c:7][c:6]1.[H.99][O:8][H:100].[Cl,Br:5][H:101]
  
  Contrast this with the "fragment marking approach"
  Reference: J.Chem.Inf. Comput. Sci., Vol 39, No. 6,1999,p.1161-1172
Daylight Chemical Information Systems Inc.