Aromaticity Perception

Aromaticity and Hückel‘s rule

OEChem TK‘s aromaticity perception routines are based around the Hückel‘s rule that defines cyclic conjugated systems with \((4N+2)\) number of \(\pi\) electrons as aromatic (where \(N\) is zero or any positive integer).

Aromaticity can be set using the OEAssignAromaticFlags function, which takes an OEMolBase argument. The OEAssignAromaticFlags sets the aromaticity flags on atoms and bonds using an aromaticity model. (For the list of available aromaticity models in OEChem TK* see section Aromaticity Models in OEChem TK. )

OEGraphMol mol = new OEGraphMol();
OEChem.OEParseSmiles(mol, "C1[NH]C=CC=1CO");


The OESmilesToMol function automatically perceives the aromaticity of the molecule using the default OEAroModel.OpenEye aromaticity model.

The following two code snippets demonstrate how to loop over aromatic atoms using the OEIsAromaticAtom functor and the IsAromatic method of the OEAtomBase class.

foreach (OEAtomBase atom in mol.GetAtoms(new OEIsAromaticAtom()))
    Console.WriteLine(atom.GetIdx() + " " +
foreach (OEAtomBase atom in mol.GetAtoms())
    if (atom.IsAromatic())
        Console.WriteLine(atom.GetIdx() + " " +

The aromatic bonds of a molecule can similarly be accessed using the OEIsAromaticBond functor and the IsAromatic method of the OEBondBase class. For more information about functors see chapter Predicate Functors.

The user can also set the atom and bond aromaticity flags manually using the OEAtomBase.SetAromatic and OEBondBase.SetAromatic methods.

Aromaticity Models in OEChem TK

The OEAssignAromaticFlags function can also take an aromaticity model constant as an argument to perceive various aromaticity models. The following aromaticity models are available in OEChem TK:

  1. OpenEye (default model)
  2. Daylight
  3. Tripos
  4. MDL
  5. MMFF

The following table demonstrates the differences between the five available aromaticity models.


Table footnotes:

[1] Atomic elements such as Te, B, Se are not available in the MMFF and Tripos aromaticity models.

[2] Only two out of the four five-membered rings are recognized as aromatic.

The code in Listing 1 demonstrates how to perceive aromaticity with these available models.

Listing 1: Aromaticity perception with various models

using System;
using OpenEye.OEChem;

public class Aromaticity 
    public static void PerceiveAromaticity(OEMolBase mol, string modelname, 
                                           uint model) 
        OEChem.OEAssignAromaticFlags(mol, model);
        string cansmi = OEChem.OECreateCanSmiString(mol);
        Console.WriteLine(modelname + " : " + cansmi);

    public static void Main(string[] args) 
        OEGraphMol mol = new OEGraphMol();
        OEChem.OESmilesToMol(mol, "c1ncncc1c2cocc2-c3[nH]ccc(=O)c3");

        PerceiveAromaticity(mol, "OEAroModelOpenEye ", OEAroModel.OpenEye);
        PerceiveAromaticity(mol, "OEAroModelDaylight", OEAroModel.Daylight);
        PerceiveAromaticity(mol, "OEAroModelTripos  ", OEAroModel.Tripos);
        PerceiveAromaticity(mol, "OEAroModelMMFF    ", OEAroModel.MMFF);
        PerceiveAromaticity(mol, "OEAroModelMDL     ", OEAroModel.MDL);

Since these models define aromaticity rules differently, the generated canonical SMILES depend on the applied aromaticity models. The output of Listing 1 is the following:

OEAroModel::OpenEye  : c1c[nH]c(cc1=O)c2cocc2c3cncnc3
OEAroModel::Daylight : c1c[nH]c(cc1=O)c2cocc2c3cncnc3
OEAroModel::Tripos   : c1c(cncn1)C2=COC=C2C3=CC(=O)C=CN3
OEAroModel::MMFF     : c1c(cncn1)c2cocc2C3=CC(=O)C=CN3
OEAroModel::MDL      : c1c(cncn1)C2=COC=C2C3=CC(=O)C=CN3

Example of aromaticity perception with different models

Clearing Aromaticity

The aromatic property of all atoms and bonds in a molecule, can conveniently be cleared (i.e. set to value false) by calling the OEClearAromaticFlags function. This is useful when writing the Kekulé form of a SMILES string, which can be done by calling OEClearAromaticFlags before calling OEKekulize and OECreateSmiString functions.

Listing 2: Clearing aromaticity

using System;
using OpenEye.OEChem;

public class ClearAromaticity 
    public static void Main(string[] argv) 
        OEGraphMol mol = new OEGraphMol();
        OEChem.OEParseSmiles(mol, "n1ccncc1");
        string smiles = OEChem.OECreateCanSmiString(mol);
        Console.WriteLine("Canonical smiles : {0}", smiles);

        smiles = OEChem.OECreateCanSmiString(mol);
        Console.WriteLine("Kekule smiles    : {0}", smiles);

The output of Listing 2 is the following:

Canonical smiles : c1cnccn1
Kekule smiles    : C1=CN=CC=N1

Input/Output Aromaticity

Since OEParseSmiles preserves the aromaticity present (or absent) in the input SMILES string, the OEClearAromaticFlags or the OEAssignAromaticFlags have to be explicitly called to remove or perceive aromaticity in a molecule, respectively. (See examples in Listing 1 and Listing 2)

However, when a molecule is imported from a file with a high-level OEReadMolecule function, atom and bond aromaticity is automatically perceived using the default OEAroModelOpenEye model.

As mentioned before (in section Molecular Property Preservation), the high-level OEWriteMolecule` writer function may automatically update atom and bond properties (including aromaticity) in order to standardize the exported molecules. The following table shows the aromaticity models associated with various file formats.

File Format Default Output Aromaticity Models
OEFormat.CAN OEAroModel.OpenEye
OEFormat.CDX OEAroModel.OpenEye
OEFormat.CSV OEAroModel.OpenEye
OEFormat.FASTA [1]
OEFormat.ISM OEAroModel.OpenEye
OEFormat.MDL OEClearAromaticFlags
OEFormat.MF [1]
OEFormat.MMOD [1]
OEFormat.MOL2 OEAroModel
OEFormat.MOL2H OEAroModel.Tripos
OEFormat.MOPAC [1]
OEFormat.OEB [1]
OEFormat.PDB [1]
OEFormat.SDF OEClearAromaticFlags
OEFormat.SLN OEAroModel.Tripos
OEFormat.SMI OEAroModel.OpenEye
OEFormat.XYZ [1]
OEFormat.INCHI [1]

Table footnote:

[1] The aromaticity model is not changed by the associated molecule writer.

The following snippet shows how to overwrite the default aromaticity model of a specific file format.

oemolostream ofs = new oemolostream(".smi");
OEChem.OEWriteMolecule(ofs, mol);  // using default OpenEye aromaticity model
uint flavor = ofs.GetFlavor(ofs.GetFormat());
flavor |= OEOFlavor.Generic.OEAroModelMDL;
ofs.SetFlavor(ofs.GetFormat(), flavor);
OEChem.OEWriteMolecule(ofs, mol);

This will produce the following output:


See also