Understanding Smiles

Understanding Smiles

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  SMILES Review
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  There are sixgeneric SMILES encoding rules, corresponding to specification of atoms, bonds, branches, ring closures, and disconnections and isomerism. SMILES RULES
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  Basics of SMILES •SMILES specifically represents a valence model of a molecule, not a computer data structure, a mathematical abstraction, or an “actual substance”. • The function of SMILES is to clearly represent a particular valence model, not dictate which one should be used. For example one chemist might represent nitromethane as C[ N+](=O)[O-] with a nitrogen of valence 4 in a charge-separated structure whereas another might represent it as CN(=O)=O with a neutral five-valent nitrogen. Both of them are correct. QUIZ : Is this a correct SMILES for nitormethane CN([O])[O]? • SMILES represents a chemist’s model of molecules, not a computer scientist’s model of a chemical data structures. • SMILES grammar is such that it may be canonicalized, i.e., among all possible valid SMILES for a given molecule or reaction, a single, canonical (unique)
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  1. Atom Specifications •The SMILES atom specification sublanguage represents the atomic properties: element identity, isotope, formal charge, and implicit hydrogen count. • Elements in the "organic subset" B, C, N, O, P, S, F, Cl, Br, and I may be written without brackets if the number of attached hydrogens conforms to the lowest normal valence consistent with explicit bonds. "Lowest normal valences" are B (3), C (4), N (3,5), O (2), P (3,5), S (2,4,6), and 1 for the halogens. • Atoms in aromatic rings are specified by lower case letters, e.g., aliphatic carbon is represented by the capital letter C, aromatic carbon by lower case c. • The symbol ‘*’ (“star” or “asterisk”) is treated by SMILES as a valid atomic symbol meaning “unspecified atomic number” and is represented as an atom of atomic number zero.
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  Examples of Atomspecifications Structure SMILES Name Remarks S [S] Elemental sulfur Defaults inside brackets: mass unspecified, charge 0, hcount 0. Au [Au] Elemental gold Second character of two-character symbols is lower case PH3 P Phosphine Lowest normal valence of phosphorus is 3 OH- [OH-] or [OH-1] Hydroxide anion If charge value is missing, 1 is assumed. i.e., ‘+’ is equivalent to ‘+1’ and ‘-’ is equivalent to ‘-1’. Fe2+ [Fe2+] or Fe[++] Iron(II) cation Charge sign may be repeated or have a signed value, e.g., ‘+-t’is equivalent to ‘+2’. 235U [235U] Uranium-235 A leading integer represents a specified atomic mass H2S S Hydrogen sulfide Lowest normal valence of sulfur is 2.
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  2. Bond Specifications •Single, double, triple, and aromatic bonds are represented in SMILES by the symbols -, =, #, and :, respectively. Adjacent atoms without an intervening symbol are connected by a valence-dictated bond (typically a single or aromatic bond). “-” (single) and “:” (aromatic) bond symbols may always be omitted on input. • There is no “preferred’ or “correct” ordering in SMILES, e.g. CCO and OCC are equally valid SMILES for ethanol. SMILES Name Emp Formula cc Ethane (CH3CH3) C=C Ethene (CH2=CH2) C#N Hydrogen Cyanide HCN CCO Ethanol CH3CH2OH
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  3.Branching Structure SMILES Name CC(C)C( =O)O Isobutyric acid FC(F)F or C(F)(F)F Fluroform ?? Perchlorate anion Branches are specified in SMILES by enclosing them in parentheses, which may be nested or stacked. First three rules (atoms, bonds, branching) allow specification of any non-cyclic molecule
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  4. Ring Specifications Takenfrom Handbook of Cheminformatics J.Gasteiger A useful way of thinking about SMILES ring specification is as follows. There is a graph theorem that says, “There is always a way of breaking one bond per ring in a connected molecule which leaves you with a still-connected but acyclic molecule.’’ (Actually, graph theoreticians talk about “graphs” instead of ‘‘molecules’’and “edges” instead of “bonds”, but if they thought about chemistry, that is how they might say it.) Pick one bond in each ring in this way, numbering them in any order. Break the numbered bonds, appending the bond number to the atoms on the ends of the bonds so broken.
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  Examples Structure SMILES Name ClCCCCClCyclohexane C1CCC=CC1 C1=CCCCC1 C1CCCC=C1 Cyclohexene c1cc2ccccc2cc1 c12c(cccc1)cccc2 C1=CC2=C(C=C1)C=CC=C2 Napthalene ?? Biphenyl
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  5. Disconnections • The‘. ‘ (“period” or “dot”) is used in SMILES to represent disconnections. In terms of the valence model being represented, the dot literally represents a bond of formal order zero: the atoms on either side of the dot are explicitly not bonded to each other. • It is often a surprise to SMILES-parser implementers that c1cc([O-].[Na+])ccc1 is a valid synonym for[Na+].[O- ]c1ccccc1.Because bonds can be specified with “ring closures”, not all SMILES which contain dots are disconnected nor are all SMILES which contain ring closures cyclic. Although somewhat perverse, C1.02.Cl2 is a valid SMILES for ethanol.
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  Isomersim • SMILES providesfor four types of specification which are so important to the molecular model that they are included even though they are outside the valence model. They are: isotopism, orientation about double bonds, stereo specification, and (for reactions) reactant-product atom mapping. These are collectively known as “isomeric SMILES”. Check http://www.daylight.com/dayhtml/doc/theory/theory.smiles.html