Re: [Cdk-devel] aromaticity detection

[Andreas S. <a.s...@ch...>]

I agree that the pyrrole nitrogen should be protonated. But it shouldn't
matter whether the hydrogen is given implicitly or explicitly.

So the difficulty is how to determine whether a nitrogen contained in a
ring is N.planar3 or N.sp2. Given the two smiles n1cccc1 and n1ccccc1
for pyrrole and pyridine the only information given are the atom
symbols, the connectivity and the aromaticity.

One solution for atom typing now is to perform a ring detection or
substructure matching on a 5-membered ring. If the nitrogen is part of a
5-ring, its configuration should be N.planar3, otherwise N.sp2. If there
are more than one nitrogens in a 5-ring, only one of them should be
N.planar3, the rest should be N.sp2. The same applied to oxygens and
sulfurs.

I guess one needs to implement a special treatment of 5-rings in order
to perform atom typing correctly.

Best wishes,
Andreas

Rajarshi Guha wrote:
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> On May 5, 2008, at 10:43 AM, Rajarshi Guha wrote:
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>> Hi, I was looking into the case of the aromaticity problem with
>> substituted pyridine derived from a SMILES string. What I see is that
>> after explicit atom typing, the ring nitrogen gets an atom type of
>> N.planar3 when the molecule is obtained from a SMILES string. But
>> when the molecule is built explicitly (via CDK source code writer)
>> the ring nitrogen is N.sp2.
>>
>> As a result, in the former case the pi electron count is of by one
>> causing armaticity detection to fail.
>>
>> So it would seem that the problem the problem is in atom typing. Can
>> anybody confirm this?
> 
> Digging more into this, since the SMILES parser is not setting bond  
> order information explicitly (all bonds appear to be single bonds),  
> the nitrogen detection method in the CDK atom type matcher assigns  
> the ring nitrogen N.planar3
> 
> It seems that the confusion is between pyrrole and pyridine - in  
> general, cases where the ring nitrogen should have a hydrogen and  
> cases where it should not.
> 
> Now if I update the code to ensure that h-count is non-zero (to take  
> into account pyrrole et al), then the pyridine case works fine. But  
> then the pyrrole test case (and 3 other related cases such as indole0  
> in the atom type tests fails. Looking at the structure that is used  
> to test pyrrole, it appears there is no explicit hydrogen.
> 
> Is that correct? I've always thought that pyrrole should have an  
> explicit H on the ring nitrogen.
> 
> - -------------------------------------------------------------------
> Rajarshi Guha  <rg...@in...>
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-- 
Andreas Schüller
PhD student in the research group of Prof. Dr. Gisbert Schneider

Johann Wolfgang Goethe University
Beilstein-endowed Chair for Chemoinformatics
Building B - 3rd floor
Siesmayerstr. 70
60323 Frankfurt am Main
Germany

Tel.: +49 69 798 24879
Fax: +49 69 798 24880
http://www.modlab.de/