Trouble with loading SMILES to QED module

[ShirosakiK]

Good day!

I am a Biochemistry undergraduate, and for my thesis I am working on designing bioinorganic complexes in silico and looking at their possible applications in medicine.

In any case, the complexes I'm working with contain an aromatic ligand sandwiched to the metal center and as you may know drawing such a bond is still a limitation in many drawing softwares. As a compromise, I directly bonded the carbons to the metal center. Subsequently, I generated the SMILES and then tried calculating its QED in RDKit. However, I get the following error even though the valence of the carbons seem to check out (please correct me if I am wrong on this). I have also tried standardizing the SMILES input but I also get the error shown.

---

from qed import qed
from rdkit import Chem
m=Chem.MolFromSmiles('CC(C)C12=C3C4=C5(C)C6=C1[Ru]143625(Cl)O=C(CC(=O1)/C=C/c1ccc(OC)c(OC)c1)/C=C/c1ccc(O)c(OC)c1')
[07:29:03] Explicit valence for atom # 3 C, 5, is greater than permitted
qed.default(m)
Error: in function properties(mol): mol argument is 'None'

---

I have also tried setting sanitize=False, and while I am now able to use the QED module, I get the following error.

---

from qed import qed
from rdkit import Chem
m=Chem.MolFromSmiles('CC(C)C12=C3C4=C5(C)C6=C1[Ru]143625(Cl)O=C(CC(=O1)/C=C/c1ccc(OC)c(OC)c1)/C=C/c1ccc(O)c(OC)c1', sanitize=False)
qed.default(m)
[07:32:01]

---

Pre-condition Violation
getNumImplicitHs() called without preceding call to calcImplicitValence()
Violation occurred on line 297 in file /home/conda/feedstock_root/build_artifacts/rdkit_1660289032136/work/Code/GraphMol/Atom.cpp
Failed Expression: d_implicitValence > -1

---

Traceback (most recent call last):
File "", line 1, in
File "/home/user/anaconda3/envs/rdkit/lib/python3.10/site-packages/qed/qed.py", line 269, in default
return weights_mean(mol, gerebtzoff)
File "/home/user/anaconda3/envs/rdkit/lib/python3.10/site-packages/qed/qed.py", line 251, in weights_mean
props = properties(mol)
File "/home/user/anaconda3/envs/rdkit/lib/python3.10/site-packages/qed/qed.py", line 207, in properties
x[0] = Descriptors.MolWt(mol) # MW
File "/home/user/anaconda3/envs/rdkit/lib/python3.10/site-packages/rdkit/Chem/Descriptors.py", line 69, in
MolWt = lambda *x, **y: _rdMolDescriptors._CalcMolWt(*x, **y)
RuntimeError: Pre-condition Violation
getNumImplicitHs() called without preceding call to calcImplicitValence()
Violation occurred on line 297 in file Code/GraphMol/Atom.cpp
Failed Expression: d_implicitValence > -1
RDKIT: 2022.03.5
BOOST: 1_74

---

Any help on how to resolve this error would be much appreciated. Thanks!

[ptosco]

@ShirosakiK Please also paste your code as text, or people willing to help will have to retype the code from your image.

[ShirosakiK]

I've updated the post to reflect the code and the error message. Thanks.

[ptosco]

@ShirosakiK
An option to preserve the integrity of the complex while avoiding to exceed the valences of carbon, nitrogen and oxygen atom involved in such complexes is to convert those single bonds into zero-order bonds:

from rdkit import Chem

m = Chem.MolFromSmiles('CC(C)C12=C3C4=C5(C)C6=C1[Ru]143625(Cl)O=C(CC(=O1)/C=C/c1ccc(OC)c(OC)c1)/C=C/c1ccc(O)c(OC)c1', sanitize=False)

for b in m.GetBonds():
    ru = None
    if b.GetBeginAtom().GetAtomicNum() == 44:
        ru = b.GetBeginAtom()
    elif b.GetEndAtom().GetAtomicNum() == 44:
        ru = b.GetEndAtom()
    if ru is None:
        continue
    other_atom = b.GetOtherAtom(ru)
    if other_atom.GetAtomicNum() in (6, 7, 8):
        b.SetBondType(Chem.BondType.ZERO)

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

Chem.MolToSmiles(m)
'COc1cc(/C=C/C2CC(/C=C/c3ccc(OC)c(OC)c3)=O~[Ru]34567(Cl)(~O=2)~c2c~3c~4(C(C)C)c~5c~6c~72C)ccc1O'

Alternatively, if you wish to preserve the dative nature of the coordination bond, you may delete the existing single bonds and re-add a dative bond pointing from the non-metal to the metal:

from rdkit import Chem

m = Chem.MolFromSmiles('CC(C)C12=C3C4=C5(C)C6=C1[Ru]143625(Cl)O=C(CC(=O1)/C=C/c1ccc(OC)c(OC)c1)/C=C/c1ccc(O)c(OC)c1', sanitize=False)

bonds_to_add = []
with Chem.RWMol(m) as m:
    for b in m.GetBonds():
        ru = None
        if b.GetBeginAtom().GetAtomicNum() == 44:
            ru = b.GetBeginAtom()
        elif b.GetEndAtom().GetAtomicNum() == 44:
            ru = b.GetEndAtom()
        if ru is None:
            continue
        other_atom = b.GetOtherAtom(ru)
        if other_atom.GetAtomicNum() in (6, 7, 8):
            m.RemoveBond(ru.GetIdx(), other_atom.GetIdx())
            bonds_to_add.append((other_atom.GetIdx(), ru.GetIdx(), Chem.BondType.DATIVE))

with Chem.RWMol(m) as m:
    for b in bonds_to_add:
        m.AddBond(*b)

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

Chem.MolToSmiles(m)
'COc1cc(/C=C/C2CC(/C=C/c3ccc(OC)c(OC)c3)=O->[Ru]34567(Cl)(<-O=2)<-c2c->3c->4(C(C)C)c->5c->6c->72C)ccc1O'

[ShirosakiK]

Thank you! I am now able to make the QED module work.