How to Sanitize mols when SanitizeMol return“ AtomKekulizeException: non-ring atom 6 marked aromatic”

[jingxingzhi]

I was trying to do an list of reactions for a mol,but the product is incorrectly labeled with aromaticity which cannot be dealed by Chem.SanitizeMol and Chem.Kekulize

from rdkit import Chem
from rdkit.Chem import Draw
from rdkit.Chem import AllChem
rxn = AllChem.ReactionFromSmarts('[#6:1]1:[#6:2]:[#6:3]:[#6:4]:[#6:5]:[#6:6]:1>>[#6:1]1=[#6:2]-[#6:3]=[#6:4]-1.[#6:6]#[#6:5]')
mol=Chem.MolFromSmiles('COc1ccc2cc3[n+](cc2c1OC)CCc1cc(O)c(O)cc1-3')
reactants = (abc,)
res=rxn.RunReactants(reactants)
Chem.SanitizeMol(res[0][0])
#Chem.Kekulize(a,clearAromaticFlags=True)#will get the same result

which return

AtomKekulizeException Traceback (most recent call last)
in
3 a=res[0][0]
4 print(Chem.MolToSmiles(a))
----> 5 Chem.Kekulize(a,clearAromaticFlags=True)
6 print(Chem.MolToSmiles(a))
7 Chem.SanitizeMol(res[0][0])

AtomKekulizeException: non-ring atom 6 marked aromatic

the smile of res[0][0] was
'COc1ccc2cc3[n+](cc2c1OC)CCc1cc(O)c(O)cc1-3'
wich should be
'C[N+]1C(CC2=CC=C2OC)-c2cc(O)c(O)cc2CC1'
How can I solve this problem

[KKLagoda]

Having the same problem, where upon a break of a bond in a polycyclic aromatic system, some, but not all atoms become aliphatic. I tried specifying the product side in all possible ways to indicate some atoms turning aliphatic, but the properties do not seem to be taken into account.

Things I have tried:

• Specifying atoms becoming aliphatic with capital letters on the product side
• Indicating their hydrogen count on the product side
• adding queries like A, !a and !R on the product side

[ptosco]

Regarding the issue described in the original post, I believe the reaction needs to specify that the bond that becomes a triple bond should not originally be part of multiple rings, as a triple bond could not form within another 6-membered ring.
If you change the reaction to:

rxn = AllChem.ReactionFromSmarts('[#6:1]1:[#6:2]:[#6:3]:[#6:4]:[#6R1:5]:[#6R1:6]:1>>[C:1]1=[C:2]-[C:3]=[C:4]-1.[C:6]#[C:5]')

then you will get sensible products.
On top of that, you may re-set aromaticity flags based on the sizes of the rings in the products, to avoid that antiaromatic rings are still labelled as aromatic.

from rdkit import Chem
from rdkit.Chem import Draw
from rdkit.Chem import AllChem
import itertools

rxn = AllChem.ReactionFromSmarts('[#6:1]1:[#6:2]:[#6:3]:[#6:4]:[#6R1:5]:[#6R1:6]:1>>[C:1]1=[C:2]-[C:3]=[C:4]-1.[C:6]#[C:5]')
rxn

mol = Chem.MolFromSmiles('COc1ccc2cc3[n+](cc2c1OC)CCc1cc(O)c(O)cc1-3')
mol

res = rxn.RunReactants((mol,))
for prod in res:
    for p in prod:
        ri = p.GetRingInfo()
        atom_rings = ri.AtomRings()
        bond_rings = ri.BondRings()
        for ring_idx, atom_ring in enumerate(atom_rings):
            bond_ring = bond_rings[ring_idx]
            is_all_sp2_ring = all(p.GetAtomWithIdx(ai).GetHybridization() == Chem.HybridizationType.SP2 for ai in atom_ring)
            n_pi_e = len(atom_ring)
            is_aromatic = (n_pi_e - 2 % 4 == 0)
            for ai in atom_ring:
                p.GetAtomWithIdx(ai).SetIsAromatic(is_aromatic)
            for bi in bond_ring:
                p.GetBondWithIdx(ai).SetIsAromatic(is_aromatic)
        for a in p.GetAtoms():
            if not a.IsInRing():
                a.SetIsAromatic(False)
        for b in p.GetBonds():
            if not b.IsInRing():
                b.SetIsAromatic(False)
        Chem.SanitizeMol(p)
Draw.MolsToGridImage(tuple(itertools.chain.from_iterable(res)), molsPerRow=6)```