Hydrogens move and stereochemistry flip when reading qcschema molecule

[ChayaSt]

@vtlim pointed out that the cmiles SMILES changed for this molecule.

client = ptl.FractalClient()

ds = client.get_collection('OptimizationDataset', 'OpenFF Full Optimization Benchmark 1')
entry = ds.get_entry(name='CO/N=C/1\C[N@](C[C@H]1C[NH3+])c2c(cc3c(=O)c(cn(c3n2)C4CC4)C(=O)[O-])F-3')
record = ds.get_record('CO/N=C/1\C[N@](C[C@H]1C[NH3+])c2c(cc3c(=O)c(cn(c3n2)C4CC4)C(=O)[O-])F-3', specification='default')
qc_mol = record.get_final_molecule()
qcjson_mol = qc_mol.dict(encoding='json')
oemol = cmiles.utils.load_molecule(qcjson_mol)

print("cmiles SMILES in database:")
print(entry.attributes['canonical_isomeric_smiles'])
print('cmiles SMILES after reading qcschema molecule')
print(cmiles.utils.mol_to_smiles(oemol, mapped=False, explicit_hydrogen=False))

Output:

cmiles SMILES in database:
CO/N=C/1\C[N@](C[C@H]1C[NH3+])c2c(cc3c(=O)c(cn(c3n2)C4CC4)C(=O)[O-])F
cmiles SMILES after reading qcschema molecule
CO/N=C/1\C[N@@H+](C[C@H]1CN)c2c(cc3c(=O)c(cn(c3n2)C4CC4)C(=O)[O-])F

There are 2 issues:

1. A hydrogen moved from the NH3+ to the pyramidal nitrogen
2. Stereochemistry changed for pyramidal nitrogen.

The first issue is fixed when this is commented out. It's not needed because cmiles already has the connectivity from the connectivity map. However, the bond is very long so openeye's perception is probably correct. These issues should be flagged with checking WBOs to see if the chemical graph changed. After investigating the second issue, it turns out that the input molecule had the pyramidal nitrogen in a planar conformation and after optimization the pyramidal nitrogen had a specified stereochemistry which was apparently different than the input SMILES.

Input molecule:

Optimized molecule:

@j-wags, I think this means that cmiles should not require defined stereochemistry for pyramidal nitrogen given that they can flip.

[ChayaSt]

When loading the qcschema molecule with rdkit, the negatively charged O gets a H to make it neutral.