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. )

mol = oechem.OEGraphMol()
oechem.OEParseSmiles(mol, "C1[NH]C=CC=1CO")
oechem.OEAssignAromaticFlags(mol)

Hint

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.

for atom in mol.GetAtoms(oechem.OEIsAromaticAtom()):
    print(atom.GetIdx(), oechem.OEGetAtomicSymbol(atom.GetAtomicNum()))

for atom in mol.GetAtoms():
    if atom.IsAromatic():
        print(atom.GetIdx(), oechem.OEGetAtomicSymbol(atom.GetAtomicNum()))

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:

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

../_images/OEAssignAromaticFlags_Table.png

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

from openeye import oechem


def PerceiveAromaticity(mol, modelname, aromodel):
    oechem.OEAssignAromaticFlags(mol, aromodel)
    cansmi = oechem.OECreateCanSmiString(mol)
    print(modelname, ":", cansmi)


mol = oechem.OEGraphMol()
oechem.OESmilesToMol(mol, "c1ncncc1c2cocc2-c3[nH]ccc(=O)c3")

PerceiveAromaticity(mol, "OEAroModelOpenEye ", oechem.OEAroModel_OpenEye)
PerceiveAromaticity(mol, "OEAroModelDaylight", oechem.OEAroModel_Daylight)
PerceiveAromaticity(mol, "OEAroModelTripos  ", oechem.OEAroModel_Tripos)
PerceiveAromaticity(mol, "OEAroModelMMFF    ", oechem.OEAroModel_MMFF)
PerceiveAromaticity(mol, "OEAroModelMDL     ", oechem.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

../_images/OEAssignAromaticFlags_Difference.png

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

from openeye import oechem

mol = oechem.OEGraphMol()
oechem.OEParseSmiles(mol, "n1ccncc1")

print("Canonical smiles :", oechem.OECreateCanSmiString(mol))
oechem.OEClearAromaticFlags(mol)
oechem.OEKekulize(mol)
print("Kekule smiles    :", oechem.OECreateCanSmiString(mol))

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]
`OEFormat_INCHIKEY`	[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.

ofs = oechem.oemolostream(".smi")
oechem.OEWriteMolecule(ofs, mol)  # using default OpenEye aromaticity model
flavor = ofs.GetFlavor(ofs.GetFormat())
flavor |= oechem.OEOFlavor_Generic_OEAroModelMDL
ofs.SetFlavor(ofs.GetFormat(), flavor)
oechem.OEWriteMolecule(ofs, mol)

This will produce the following output:

c1c[nH]cc1CO
C1=CNC=C1CO