Basic aromatization and ambiguous aromaticity 5-member rings

Hi,

Given the following four structures in a table with Aromatization set to Basic in the Standardizer
1. CN(CCCN)C(=O)CCN1C(=O)C=NC2=C1C=CC=C2
2. NC1=CN(CCN2C(=O)C=NC3=C2C=CC=C3)C(=O)C=C1
3. O=C1NC2=C(C=CC=C2)N=C1
4. CN1C(=O)C=NC2=C1C=CC=C2
and performing Substructure search with the structure number 4 as a query and default search options we get no hits. In order to pinpoint the problem the following searches were performed.

1. Query structure number 4, Substructure search, 'Vague Bond' set to 'Off' - three hits as expected.
2. Query structure number 4, Full search, either 'Vague Bond' option - exactly one hit as expected.
3. Query structure 'CCN1C(=O)C=NC2=CC=CC=C12', Substructure search, either 'Vague Bond' option - two hits as expected.
4. Query structure number 3, Substructure search, either 'Vague Bond' option - three hits as expected.
5. Once again, query structure number 4, Substructure search, 'Vague Bond' set to 'Ambiguous aromaticity 5-membered rings' by default - no hits, expected three.

I guess the question is how a single methyl group on 6-membered ring in the structure number 4 and the 'Ambiguous aromaticity 5-membered rings' option are connected.

As a side note, all of the above happens only with Basic aromaticity on a table.

Thanks.

The environment is
Oracle Database 11g Release 11.2.0.1.0 - 64bit Production
PL/SQL Release 11.2.0.1.0 - Production
CORE 11.2.0.1.0 Production
TNS for 64-bit Windows: Version 11.2.0.1.0 - Production
NLSRTL Version 11.2.0.1.0 - Production
JChem Server environment:
Java VM vendor: Sun Microsystems Inc.
Java version: 1.6.0_20
Java VM version: 16.3-b01
JChem version: 5.3.3
JChem Index version: 5030300
JDBC driver version: 11.1.0.7.0-Production

Hi Valery,

 

Thank you for the bug report. I could reproduce this. We will check what is going on.

 

Best regards,

Szabolcs

Hi Szabolcs,

We stumbled upon two more structures that behave the way described above, i.e. return no hits on substructure search with 'Vague Bond' set to 'Ambiguous aromaticity 5-membered rings' and 'Basic' aromatization on the structure table, but do return itself on full search.
1. OC1=C(\C=N\C2=CNC(=O)NC2=O)C=C(Cl)C=C1
2. OC1=C(C=C(Br)C=C1)C1=CC(C2=CC=CC=C2)=C(C#N)C(=O)N1
The two above are falling out of the *N1C(=O)C(*)=NC2=C1C=CC=C2 pattern. I guess there are more structural features that break the search.

Cheers,
Valery

Hi Valery,

 

Thanks for these structures as well. Although not exactly the same ring system, the bug is the same, I think.

We will let you know when it is fixed.

 

Best regards,

Szabolcs

Hi Szabolcs,

Are there any news on the matter? Any ideas on a workaround that doesn't involve the changes to the table and search options?

Thanks,
Valery

Hi Valery

We spotted the bug during handling of 5membered rings ambiguous aromaticity (vague bond level-1), the general aromatized molecule is calculated and used for searching. We will fix that bug in the next minor release, version 5.3.7. 

Is this suitable for you?

Regards,

Robert

Hi Robert,

I guess we don't have much of a choice, unless you know a way we could use right now to force JChemSearcher to do correct aromatization during the search.

Thanks,
Valery

Dear Robert and Szabolcs,

Although the Release Note for 5.3.6 states that 'Vague bond level 1 misses hit when basic aromatization is used' bug was fixed, in all the tests it behaves exactly the same way as previous version when it comes to tables with Basic Aromatization. Could you please recreate test conditions of the original problem and see if the bug was actually fixed? So far I haven't managed to get expected results.

Cheers,
Valery

Hello,

You are right the bug isn't corrected yet. This is an error in the release notes, it's my earlier comment on this topic that's correct not the notes. The bug has been fixed but couldn't fit in this release and will be released in 5.3.7. 

Sorry for the inconvenience.

Bye,

Robert

Hey guys,

It seems the bug wasn't fixed in neither 5.3.7 nor 5.3.8.
Any estimate on as to when?

Cheers,
Valery.

Hi Valery,

Do you specify standardizer configuration with an xml file? If yes then we have found the cause of the incorrect fix.

We do appologize for this incorrect fix, we checked this case with a standardizer configuration given in its short form ("standardize:b").

e.g. jcsearch --standardize "aromatize:b" -q 'CN1C(=O)C=NC2=C1C=CC=C2' 'CN(CCCN)C(=O)CCN1C(=O)C=NC2=C1C=CC=C2'

gives hit. In case of an xml configuration during handling 5-membered ambiguous aromaticity rings it's not recognized that basic aromatization should be used.

We will fix the bug with the xml configuration and return here when it's ready.

Bye,

Robert

Hi,

Some notes to the previous post.

Basic aromatization standardizer configuration and 5-membered ambiguous rings:

The one-line standardizer configuration version works in 5.3.8 in case of memory searches. For DB searches  this was corrected in 5.4.

We are now working on the correct handling of the xml configuration file.

Bye,

Robert

Hi Robers,

The original bug report was about a search on JChemBase table with standardizer config applied upon its creation. I guess that what's you call XML configuration. Both IJC and JChemSearch class behave identically.

And what did you mean by 'For DB searches  this was corrected in 5.4.'?

Cheers,
Valery

Hi,

It's about DB searches where the Standardizer is created with API and the configuration is specified by one-line strings like "aromatize:b" and not by an xml configuration file.

Bye,

Robert

Hi,

The bug with basic aromatization specified with an xml string/file will be fixed in version 5.4.1 both for memory and database.

Bye,

Robert

Hi Robert,

Could you please re-run the search steps on the configuration described in my original post from 15 June using jchem-5.4.0.1 and confirm the bug is solved?

As far as I can see, the search number 5 is still failing to produce any results.

I would like you to take a close look on it once again.

Regards,
Valery

Hi Valery,

Could you please re-run the search steps on the configuration described in my original post from 15 June using jchem-5.4.0.1 and confirm the bug is solved?

 

Just to prevent a possible misunderstanding about versions:

Did you try with 5.4.0.1  or 5.4.1 (the latter was just released yesterday) ?

Please note the fix is only in 5.4.1.

(I see you were trying with 5.3.3 originally, since then there might have been partial improvements even in the earlier 5.4.0.1)

Best,

Szilard

Hi Valery,

I checked and it works.

Could you possibly try the following script with the attached files:

jcman c test --stconfig basicArom.xml

jcman a test basic_arom_table.smiles

jcsearch -q "CN(CCCN)C(=O)CCN1C(=O)C=NC2=C1C=CC=C2" DB:test

jcsearch -q "NC1=CN(CCN2C(=O)C=Nc3ccccc23)C(=O)C=C1" DB:test

jcsearch -q "O=C1NC2=C(C=CC=C2)N=C1" DB:test

jcsearch -q "CN1C(=O)C=NC2=C1C=CC=C2" DB:test

 

What are the outputs of these searches for you?

The first two should retrieve itself only, the third all 4 records while the fourth all except the 3rd query.

Do you obtain different results for this test?

Bye,

Robert

Hi,

I checked with 5.4.1 and it works indeed.
Looks like in 5.4.0.1 the fix wasn't included yet.

Thank you guys.