Hi Alexis,
The chiral substructure match does not look at the CIP labels, but rather
at the atom parities, as you expected.
In the examples below I have reordered your mol_structure as it makes
things easier to understand.
Let's work with a fragment constructed from SMILES rather than from SMARTS:
from rdkit import Chem
from rdkit.Chem.Draw import IPythonConsole
IPythonConsole.drawOptions.addAtomIndices = True
mol_structure = Chem.MolFromSmiles("C[C@](N)1CCCN(C1)C(C)=O")
mol_structure
[image: image.png]
mol_frag = Chem.MolFromSmiles("C[C@H]1CCCN(C1)C(C)=O")
mol_frag
[image: image.png]
In this case, the chiral tags are both CW and we have a match, and the fact
that the CIP chirality is opposite is not relevant, as you would expect:
print("mol_structure", mol_structure.GetAtomWithIdx(1).GetChiralTag(),
mol_structure.GetAtomWithIdx(1).GetProp("_CIPCode"))
print("mol_frag", mol_frag.GetAtomWithIdx(1).GetChiralTag(),
mol_frag.GetAtomWithIdx(1).GetProp("_CIPCode"))
print(mol_structure.HasSubstructMatch(mol_frag, useChirality=True))
mol_structure CHI_TETRAHEDRAL_CW R
mol_frag CHI_TETRAHEDRAL_CW S
True
If we reverse the parity, the CIP chirality becomes identical, but as
expected this time the substructure match fails:
mol_frag = Chem.MolFromSmiles("C[C@@H]1CCCN(C1)C(C)=O")
mol_frag
[image: image.png]
print("mol_structure", mol_structure.GetAtomWithIdx(1).GetChiralTag(),
mol_structure.GetAtomWithIdx(1).GetProp("_CIPCode"))
print("mol_frag", mol_frag.GetAtomWithIdx(1).GetChiralTag(),
mol_frag.GetAtomWithIdx(1).GetProp("_CIPCode"))
print(mol_structure.HasSubstructMatch(mol_frag, useChirality=True))
mol_structure CHI_TETRAHEDRAL_CW R
mol_frag CHI_TETRAHEDRAL_CCW R
False
I believe the above matches your expectations.
Let's now see what happens when we switch to a fragment constructed from
SMARTS:
mol_frag = Chem.MolFromSmarts("C[C@]1CCCN(C1)C(C)=O")
mol_frag
[image: image.png]
In this case, the chiral center has only 3 neighbors: in fact, there is no
implicit H as there was in the fragment constructed from SMILES; the 4th
substituent is simply not defined by the SMARTS string.
When we look at the chiral tag assigned by RDKit, we see that this time the
chiral tag is CCW, while the matching atom in mol_structure is CW; this is
why the match fails:
print("mol_structure", mol_structure.GetAtomWithIdx(1).GetChiralTag())
print("mol_frag", mol_frag.GetAtomWithIdx(1).GetChiralTag())
print(mol_structure.HasSubstructMatch(mol_frag, useChirality=True))
mol_structure CHI_TETRAHEDRAL_CW
mol_frag CHI_TETRAHEDRAL_CCW
False
My guess is that in this case atom 1 is assigned a CCW parity because this
is what is specified in the SMARTS string with the @ symbol; given that
there are less than 3 bonds, the parity cannot be determined based on bond
indices as normally happens, so I guess the parity is simply set based on
what is specified by the user in the SMARTS string, e.g.:
mol_frag = Chem.MolFromSmarts("[C@@]")
print("mol_frag", mol_frag.GetAtomWithIdx(0).GetChiralTag())
mol_frag CHI_TETRAHEDRAL_CW
mol_frag = Chem.MolFromSmarts("[C@]")
print("mol_frag", mol_frag.GetAtomWithIdx(0).GetChiralTag())
mol_frag CHI_TETRAHEDRAL_CCW
Maybe Greg can shed more light on this.
Cheers,
p.
On Tue, Jan 4, 2022 at 1:07 PM Alexis Parenty <alexis.parenty.h...@gmail.com>
wrote:
> Hi Shani,
> Many thanks for your response. Good observation! I did not realise that
> the stereoisomer nomenclature had swap on removing the amine. However, is
> it the intended behaviour of the method?
> To me, in that case, the S stereoisomer fragment should match the R
> stereoisomer super structure but it does not. The R stereoisomer fragment
> matches the R stereoisomer super structure when It should not. What do you
> think?
>
> Best,
>
> Alexis
>
>
>
> On Tue, 4 Jan 2022 at 12:42, Shani Zev <levishan...@gmail.com> wrote:
>
>> Hi Alexis,
>> I think that the reason for this is because in the first case you are
>> comparing S and R stereoisomer and hence it is false while in the second
>> you are comparing R and R.
>> best,
>> Shani
>>
>> [image: q.gif]
>>
>> On Tue, Jan 4, 2022 at 1:22 PM Alexis Parenty <
>> alexis.parenty.h...@gmail.com> wrote:
>>
>>> Hi everyone,
>>>
>>> Why is it that the following smarts C[C@]1CCCN(C1)C(C)=O does not match
>>> the following structure C[C@]1(CCCN(C1)C(C)=O)N when using the
>>> chirality argument in the HasSubstructMatch method?
>>>
>>> mol_frag = Chem.MolFromSmarts("C[C@]1CCCN(C1)C(C)=O")
>>> mol_structure = Chem.MolFromSmiles("C[C@]1(CCCN(C1)C(C)=O)N")
>>>
>>> print(mol_structure.HasSubstructMatch(mol_frag, useChirality=True))
>>> ==> False
>>>
>>>
>>> worst, the other isomeric fragment matches when it should not:
>>>
>>> mol_frag = Chem.MolFromSmarts("C[C@@]1CCCN(C1)C(C)=O")
>>> mol_structure = Chem.MolFromSmiles("C[C@]1(CCCN(C1)C(C)=O)N")
>>>
>>> print(mol_structure.HasSubstructMatch(mol_frag, useChirality=True))
>>> ==> True
>>>
>>> Am I missing something?
>>>
>>> Many thanks,
>>>
>>> Alexis
>>> _______________________________________________
>>> Rdkit-discuss mailing list
>>> Rdkit-discuss@lists.sourceforge.net
>>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>>
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