Different Bond Types between Similar Molecules

vsomnath commented 4 years ago

**Configuration:**

RDKit Version: 2019.03.4
Operating system: Ubuntu 18.04
Python version (if relevant): 3.7.3
Are you using conda? Yes
If you are using conda, which channel did you install the rdkit from? conda-forge
If you are not using conda: how did you install the RDKit?

Description:

I'm working on a task of graph translation from fragment molecules to reactant molecules. These atom mapped SMILES come from the USPTO reaction dataset. If you see the code below, the bond between atoms with atom map numbers 45 and 46 have different bond types, even though they are both aromatic, or double. Attached below are also the images of the fragments and reactants. The molecules look the same except for the -OH group with atom map number 47.

Fragment

Reactant

from rdkit import Chem

frag_smi = '[CH3:34][O:35][C:36]([CH2:37][c:38]1[cH:39][n:40]([CH3:48])[c:41]2[cH:42][c+:43][cH:44][cH:45][c:46]12)=[O:49]'

reac_smi = '[CH3:34][O:35][C:36]([CH2:37][c:38]1[cH:39][n:40]([CH3:48])[c:41]2[cH:42][c:43]([OH:47])[cH:44][cH:45][c:46]12)=[O:49]'

frag_mol = Chem.MolFromSmiles(frag_smi)
reac_mol = Chem.MolFromSmiles(reac_smi)

print(frag_mol.GetAtomWithIdx(12).GetAtomMapNum(), frag_mol.GetAtomWithIdx(13).GetAtomMapNum())
print(frag_mol.GetBondBetweenAtoms(12, 13).GetBondType())
print()

print(reac_mol.GetAtomWithIdx(13).GetAtomMapNum(), reac_mol.GetAtomWithIdx(14).GetAtomMapNum())
print(reac_mol.GetBondBetweenAtoms(13, 14).GetBondType())

Output:

45 46
DOUBLE

45 46
AROMATIC

I'd like to understand why this is happening, and if there is something on my end, like using the +ve charge on the fragment that is leading to this issue.

vsomnath commented 4 years ago

When I remove the positive charge, both bonds are marked as Aromatic. That seems to be the problem, but the positive charge indication is important for my task, as I use the atom.GetFormalCharge() as a feature in the graph model.

ptosco commented 4 years ago

It looks like setting the phenyl ring to be a carbocation removes the aromatic flag from the ring atoms and bonds, which does not seem right.

frag_noh = "COC(=O)Cc1cn(C)c2ccccc12"
frag_noh_mol = Chem.MolFromSmiles(frag_noh)
Chem.MolToSmiles(frag_noh_mol)
'COC(=O)Cc1cn(C)c2ccccc12'

frag_noh_mol.GetAtomWithIdx(11).SetNumExplicitHs(0)
frag_noh_mol.GetAtomWithIdx(11).SetNoImplicit(True)
frag_noh_mol.GetAtomWithIdx(11).SetFormalCharge(1)
frag_noh_mol.GetAtomWithIdx(11).UpdatePropertyCache()

Chem.SanitizeMol(frag_noh_mol)
rdkit.Chem.rdmolops.SanitizeFlags.SANITIZE_NONE

Chem.MolToSmiles(frag_noh_mol)
'COC(=O)Cc1cn(C)c2c1=CC=[C+]C=2'

greglandrum commented 4 years ago

I think there's a good argument that this is a bug. The [C+] is iso-electronic to a [B] and should be happily aromatic in this situation. Here's a simpler demonstration:

In [10]: m = Chem.MolFromSmiles('C1=CC=CC=[C+]1')                                                                                                                          

In [11]: m.Debug()                                                                                                                                                         
Atoms:
    0 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 0 chi: 0
    1 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 0 chi: 0
    2 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 0 chi: 0
    3 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 0 chi: 0
    4 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 0 chi: 0
    5 6 C chg: 1  deg: 2 exp: 3 imp: 0 hyb: 2 arom?: 0 chi: 0
Bonds:
    0 0->1 order: 2 conj?: 1 aromatic?: 0
    1 1->2 order: 1 conj?: 1 aromatic?: 0
    2 2->3 order: 2 conj?: 1 aromatic?: 0
    3 3->4 order: 1 conj?: 1 aromatic?: 0
    4 4->5 order: 2 conj?: 1 aromatic?: 0
    5 5->0 order: 1 conj?: 1 aromatic?: 0

In [12]: m = Chem.MolFromSmiles('C1=CC=CC=B1')                                                                                                                             

In [13]: m.Debug()                                                                                                                                                         
Atoms:
    0 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 1 chi: 0
    1 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 1 chi: 0
    2 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 1 chi: 0
    3 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 1 chi: 0
    4 6 C chg: 0  deg: 2 exp: 3 imp: 1 hyb: 3 arom?: 1 chi: 0
    5 5 B chg: 0  deg: 2 exp: 3 imp: 0 hyb: 2 arom?: 1 chi: 0
Bonds:
    0 0->1 order: 12 conj?: 1 aromatic?: 1
    1 1->2 order: 12 conj?: 1 aromatic?: 1
    2 2->3 order: 12 conj?: 1 aromatic?: 1
    3 3->4 order: 12 conj?: 1 aromatic?: 1
    4 4->5 order: 12 conj?: 1 aromatic?: 1
    5 5->0 order: 12 conj?: 1 aromatic?: 1

In [14]:

rdkit / rdkit

Different Bond Types between Similar Molecules #2808