ERROR SMARTS matching SMILES

[simonmb]

Description:

• RDKit Version: 2017.09.3
• Platform: Windows

When matching one SMARTS with a specific SMILES somehow one match is missing.

Following code:

smiles = 'C1=CC=C2C(=C1)C3=CC=CC4=C3C5=C(C=C4)C(C(C=C25)O)O'
mol = Chem.MolFromSmiles(smiles)

q = Chem.MolFromSmarts('[cH]')

mol.GetSubstructMatches(q)

returns:
((0,), (1,), (2,), (5,), (7,), (8,), (9,), (14,), (15,))

It returns 9 hits, although it should find 10. Atom with index 18 is missing. If I draw the image the aromaticity looks correct:

[simonmb]

Found another one:

mol = Chem.MolFromSmiles('CN1C2=CC=CC=C2C=C3C1=CC4=CC=CC=C43') mol.HasSubstructMatch(Chem.MolFromSmarts('[CH3]N'))

returns False (should be True)

Again image suggests it should work:

[bp-kelley]

The nitrogen is aromatic which is why it isn't matching. This is, in general, why using atomic numbers can be better than using symbols. Both the following also match. pat = Chem.MolFromSmarts('[CH3]n') pat = Chem.MolFromSmarts('[#6&H3][#7]')

…

On Fri, Aug 24, 2018 at 8:05 AM Simon ***@***.***> wrote: Found another one: mol = Chem.MolFromSmiles('CN1C2=CC=CC=C2C=C3C1=CC4=CC=CC=C43') mol.HasSubstructMatch(Chem.MolFromSmarts('[CH3]N')) returns False (should be True) Again image suggests it should work: [image: test] <https://user-images.githubusercontent.com/6115499/44583653-712d3d00-a7a6-11e8-864e-c21998c66942.png> — You are receiving this because you are subscribed to this thread. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioCm95BbShtbxX2gjDQekgCtX6rzxks5uT-wCgaJpZM4WK_DE> .

[simonmb]

Yes, in the 2nd example it is due to aromaticity. Thank you for your help. But why doesn't this work?

Chem.MolFromSmiles('C=C1C=CC=CC1=C').HasSubstructMatch(Chem.MolFromSmarts('[#6&H]=[#6&H]'))

[bp-kelley]

Carbon only has four valence electrons, the pattern that will match is '[#6&H0]=[#6&H2]"

…

On Fri, Aug 24, 2018 at 8:38 AM Simon ***@***.***> wrote: Yes, in the 2nd example it is due to aromaticity. Thank you for your help. But why doesn't *this* work? Chem.MolFromSmiles('C=C1C=CC=CC1=C').HasSubstructMatch(Chem.MolFromSmarts('[#6&H]=[#6&H]')) [image: test] <https://user-images.githubusercontent.com/6115499/44585013-22ce6d00-a7ab-11e8-9dea-be9cc4e4b805.png> — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioCDh9HNhWHRLsZ_BvVZTGXexETQwks5uT_PBgaJpZM4WK_DE> .

[simonmb]

I actually ment to match this:

[bp-kelley]

This is subtler, the ring is aromatic. RDKit doesn't store both the aromatic and double bond types, they are independent. The matching patterns are: pat = Chem.MolFromSmarts("[#6&H1]:[#6&H1]") or pat = Chem.MolFromSmarts("[#6&H1]~[#6&H1]") ~ is any bond, : is aromatic. Or you could use, pat = Chem.MolFromSmarts("[#6&H1]-,=,:[#6&H1]") depending. Cheers, Brian

…

On Fri, Aug 24, 2018 at 10:30 AM Simon ***@***.***> wrote: I actually ment to match this: [image: unbenannt] <https://user-images.githubusercontent.com/6115499/44590242-fae70580-a7ba-11e8-99fb-3bc6320337c8.png> — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioLQdnw4-y8J0kv6dxMfMDo-tTvQQks5uUA4egaJpZM4WK_DE> .

[bp-kelley]

I will say this is one of those corner cases where if you draw the ring as aromatic, it sure looks like there are five bonds to a carbon which makes some of my medicinal chemistry friends look a bit queasy. Cheers, Brian

…

On Fri, Aug 24, 2018 at 10:36 AM Brian Kelley ***@***.***> wrote: This is subtler, the ring is aromatic. RDKit doesn't store both the aromatic and double bond types, they are independent. The matching patterns are: pat = Chem.MolFromSmarts("[#6&H1]:[#6&H1]") or pat = Chem.MolFromSmarts("[#6&H1]~[#6&H1]") ~ is any bond, : is aromatic. Or you could use, pat = Chem.MolFromSmarts("[#6&H1]-,=,:[#6&H1]") depending. Cheers, Brian On Fri, Aug 24, 2018 at 10:30 AM Simon ***@***.***> wrote: > I actually ment to match this: > > [image: unbenannt] > <https://user-images.githubusercontent.com/6115499/44590242-fae70580-a7ba-11e8-99fb-3bc6320337c8.png> > > — > You are receiving this because you commented. > Reply to this email directly, view it on GitHub > <#2011 (comment)>, or mute > the thread > <https://github.com/notifications/unsubscribe-auth/AJbioLQdnw4-y8J0kv6dxMfMDo-tTvQQks5uUA4egaJpZM4WK_DE> > . >

[simonmb]

Thank you for clarifying this, I was not aware of this fact:

RDKit doesn't store both the aromatic and double bond types, they are independent.

The problem with the first example IMHO is one of aromaticity.
I found another smiles:
C1=CC=C2C(=C1)C=C3C4=CC=CC4=CC5=C3C2=CC=C5

for which the SMARTS '[cH]' gives less matches than I would expect. It returns 9 instead of the expected 12. Or am I commiting some mistake?

[simonmb]

I found a workaround. If I match:
[$([#6&H1&R](=[#6&R])[#6&R])]

I get the missing matches. But isn't this an error? Somehow some atoms are not beeing marked as aromatic.

[simonmb]

I found another error for a SMARTS equal to the SMILES:

mol = Chem.MolFromSmiles('C1=COC(=C1)C=O)
patt = Chem.MolFromSmarts('C1=COC(=C1)C=O')
mol.GetSubstructMatches(patt)
returns empty

[bp-kelley]

SMARTS has no aromaticity model and is very literal. In all your cases where it doesn't match, you are having aromaticity mismatches. You can see this as follows:

>> mol = Chem.MolFromSmiles('C1=COC(=C1)C=O') >> Chem.MolToSmiles(mol)

'O=Cc1ccco1' Since RDKit doesn't support both a kekule and aromaticity model simultaneously, this simply isn't going to match. I suggest reading this: http://www.daylight.com/dayhtml/doc/theory/theory.smarts.html specifically the smarts vs smiles section. Cheers, Brian

…

On Mon, Aug 27, 2018 at 4:39 AM Simon ***@***.***> wrote: I found another error for a SMARTS equal to the SMILES: mol = Chem.MolFromSmiles('C1=COC(=C1)C=O) patt = Chem.MolFromSmarts('C1=COC(=C1)C=O') mol.GetSubstructMatches(patt) returns empty [image: clipboard01] <https://user-images.githubusercontent.com/6115499/44649795-2f3e0a00-a9e5-11e8-8b12-b406cd0b018a.png> — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioGEUK42JfqcbKS3-ulX_08crTIwvks5uU7ArgaJpZM4WK_DE> .

[simonmb]

Thanks Brian, I see what the problem is. Thanks for the link.

How does rdkit decide which atoms to aromatize?

Shouldn't all of the atoms in the following SMILES be considered aromatic?
C1=CC=C2C(=C1)C=C3C4=CC=CC4=CC5=C3C2=CC=C5
I dont get all the matches for '[cH1]', as I described above. The same applies to the furfural (which you referred to in your las comment).

[bp-kelley]

There is one five membered ring that doesn't look like it to me (hopefully the image transfers) [image: image.png]

>> from rdkit import Chem >> m = Chem.MolFromSmiles("C1=CC=C2C(=C1)C=C3C4=CC=CC4=CC5=C3C2=CC=C5") >> Chem.MolToSmiles(m)

'C1=Cc2cc3cccc4c5ccccc5cc(c2=C1)c34'

…

On Mon, Aug 27, 2018 at 12:31 PM Simon ***@***.***> wrote: Thanks Brian, I see what the problem is. Thanks for the link. *How does rdkit decide which atoms to aromatize?* Shouldn't all of the atoms in the following SMILES be considered aromatic? C1=CC=C2C(=C1)C=C3C4=CC=CC4=CC5=C3C2=CC=C5 I dont get all the matches for '[cH1]', as I described above. The same applies to the furfural (which you referred to in your las comment). — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioO5NQKjRAdFDvgAd29L8WukV3vntks5uVB7hgaJpZM4WK_DE> .

[simonmb]

Unfortunately, the image did not transfer.
I was reading about the aromaticity here.
Looking at the examples shown there I would think all the atoms in the molecule should be aromatic. But I am no expert...
What do you say?

[bp-kelley]

As I said, RDKit doesn't consider the five membered ring to be aromatic. I'm attaching a PNG, hopefully you can see this. [image: aromaticity.png]

…

On Tue, Aug 28, 2018 at 2:10 AM Simon ***@***.***> wrote: Unfortunately, the image did not transfer. I was reading about the aromaticity here <https://www.rdkit.org/docs/RDKit_Book.html>. Looking at the examples shown there I would think all the atoms in the molecule should be aromatic. But I am no expert... What do you say? — You are receiving this because you commented. Reply to this email directly, view it on GitHub <#2011 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/AJbioHmjii4vMNk_gZ-oLjXlRJeiNLmIks5uVN6-gaJpZM4WK_DE> .