Tautomer canonicalization loses track of chirality

[xavierholt]

Describe the Bug
In some cases, a molecule with explicit chirality loses its chirality after being run through rdMolStandardize.CanonicalTautomer() or TautomerEnumerator.Canonicalize(). This seems to happen when an atom next to the chiral center has double bonds (maybe only with ketones, amides, etc?).

To Reproduce

# A really simple test function:
from rdkit.Chem import MolFromSmiles, MolToSmiles
from rdkit.Chem.MolStandardize.rdMolStandardize import CanonicalTautomer
def demo(smiles):
    mol = MolFromSmiles(smiles)
    mol = CanonicalTautomer(mol)
    print(MolToSmiles(mol))

# These work as expected:
demo('NC[C@H](Cl)F')
# -> NC[C@@H](F)Cl
demo('NC[C@@H](Cl)F')
# -> NC[C@H](F)Cl

# These don't:
demo('NC(=O)[C@H](Cl)F')
# -> NC(=O)C(F)Cl
demo('NC(=O)[C@@H](Cl)F')
# -> NC(=O)C(F)Cl

# A few more test cases (only the second preserves chirality):
demo('NC(=C)[C@@H](Cl)F')
# -> CC(=N)C(F)Cl
demo('C(=C)[C@@H](Cl)F')
# -> C=C[C@H](F)Cl
demo ('C(=O)[C@@H](Cl)F')
# -> O=CC(F)Cl

Expected Behavior
Explicit chiral centers should remain chiral (unless this doesn't make sense in the canonical tautomer).

Configuration

• RDKit version: 2024.9.6
• OS: Ubuntu 22.04 (in Docker)
• Python version: 3.10.12
• Are you using conda? No

[pechersky]

There is a SetRemoveSp3Stereo option on TautomerEnumerator. This makes all your examples work:

from rdkit.Chem import MolFromSmiles, MolToSmiles
from rdkit.Chem.MolStandardize.rdMolStandardize import TautomerEnumerator

def demo(smiles):
    mol = MolFromSmiles(smiles)
    enumerator = TautomerEnumerator()
    enumerator.SetRemoveSp3Stereo(False)
    mol = enumerator.Canonicalize(mol)
    print(MolToSmiles(mol))

[xavierholt]

@pechersky - Thanks for that! I was not aware of that option. Maybe this isn't a bug after all - the default isn't what I expected, but if this is the intended behavior feel free to close this.

[github-actions]

This issue was marked as stale because it has been open for 90 days with no activity.

[github-actions]

This issue was closed because it has been inactive for 14 days since being marked as stale.