Styjun

Sanitization error while applying a reaction to an molecule with wedged bond.
I am getting this error while applying a proton removal reaction to a molecule but I do not see any error in MolBlock information.

This is for a reaction problem in which I am trying to apply a simple reaction (proton removal) to a molecule given its isomeric SMILES.

I create a function to apply reaction using SMARTS and SMILES but I am getting the following error which I could not fixed.

I am using the following code to load my inputs.

smile = rdkit.Chem.rdmolfiles.MolToSmiles(mol,isomericSmiles=True)

which leads to:

C/C1=C\C[C@@H]([C+](C)C)CC/C(C)=C/CC1

I create the following dictionary to use my SMILES and SMARTS:

reaction_smarts = 

# proton removal reaction

reaction_smarts["proton_removal"] = "[Ch:1]-[C+1:2]>>[C:1]=[C+0:2].[H+]" 

reactions = name: AllChem.ReactionFromSmarts(reaction_smarts[name]) for name in reaction_smarts

# function to run reactions

def run_reaction(molecule, reaction):
 products = []
 for product in reaction.RunReactant(molecule, 0):
 Chem.SanitizeMol(product[0])
 products.append(product[0])
 return products

# apply reaction


products = run_reaction(cation_to_rdkit_mol["mol_name"], reactions["proton_removal"])

At this step I am getting this error but I cannot fix it.
RDKit ERROR: [10:43:23] Explicit valence for atom # 0 C, 5, is greater than permitted

Expected results should be the the molecule with the double bond and its stereoisomers:

First product: CC(C)=C1C/C=C(\C)CC/C=C(\C)CC1

Second product: C=C(C)[C@@H]1C/C=C(\C)CC/C=C(\C)CC1

Third product: C=C(C)[C@H]1C/C=C(\C)CC/C=C(\C)CC1

I am using Chem.EnumerateStereoisomers.EnumerateStereoisomers() to get all stereoisomers but I am just getting the first and second product. I also added your initial proposal product[0].GetAtomWithIdx(0).SetNumExplicitHs(0) which actually fix the Explicit valence error. But now I am trying to figure it out how to get all that three stereoisomers.

Any hint why this is happening?, cause if I check the mol block with all the info about valence it seems to be fine.

The Error is stating that the Explicit valence for atom 0 (Carbon) is 5, this would suggest that the explicit hydrogen hasn't been removed although the bond is now a double bond, hence a valence of 5. I am not too familiar with reaction SMARTS although an easy way to fix this manually would be to set the number of explicit hydrogens on atom 0 to 0 before you sanitize:

product.GetAtomWithIdx(0).SetNumExplicitHs(0)
Chem.SanitizeMol(product)

Edit 1:
Scratch that, I did some experimentation, try this reaction:

rxn = AllChem.ReactionFromSmarts('[#6@@H:1]-[#6+:2] >> [#6H0:1]=[#6+0:2]')

This way in the reaction definition we explicitly state that a hydrogen is lost and the resultant molecule will sanitize. Does this work for you?

Edit 2:
When I run this reaction the product does not seem to contain a cation:

mol = Chem.MolFromSmiles('C/C1=C\C[C@@H]([C+](C)C)CC/C(C)=C/CC1')
rxn = AllChem.ReactionFromSmarts('[#6@@H:1]-[#6+:2] >> [#6H0:1]=[#6+0:2]')
products = list()
for product in rxn.RunReactant(mol, 0):
 Chem.SanitizeMol(product[0])
 products.append(product[0])
print(Chem.MolToSmiles(products[0]))

Output:
'CC(C)=C1C/C=C(\C)CC/C=C(\C)CC1'

Edit 3:
I think I now understand what you are looking for:

mol = Chem.MolFromSmiles('C/C1=C\C[C@@H]([C+](C)C)CC/C(C)=C/CC1')

# Reactant SMARTS
reactant_smarts = '[CH3:1][C+:2][C@@H:3]'

# Product SMARTS
product_smarts = [
'[CH2:1]=[CH0+0:2][CH:3]',
'[CH2:1]=[CH0+0:2][C@H:3]',
'[CH2:1]=[CH0+0:2][C@@H:3]',
]

# Reaction SMARTS
reaction_smarts = str(reactant_smarts + '>>' + '.'.join(product_smarts))

# RDKit Reaction
rxn = AllChem.ReactionFromSmarts(reaction_smarts)

# Get Products
results = list()
for products in rxn.RunReactant(mol, 0):
 for product in products:
 Chem.SanitizeMol(product)
 results.append(product)
 print(Chem.MolToSmiles(product))

Output:
'C=C(C)C1C/C=C(\C)CC/C=C(\C)CC1'
'C=C(C)[C@H]1C/C=C(\C)CC/C=C(\C)CC1'
'C=C(C)[C@@H]1C/C=C(\C)CC/C=C(\C)CC1'
'C=C(C)C1C/C=C(\C)CC/C=C(\C)CC1'
'C=C(C)[C@H]1C/C=C(\C)CC/C=C(\C)CC1'
'C=C(C)[C@@H]1C/C=C(\C)CC/C=C(\C)CC1'

Note that we get the same products twice, I think this is because the reactant SMARTS matches both CH3 groups, hence the reaction is applied to both. I hope this is what you are looking for.