Standardization Error?

Good morning,





When standardizing compounds with carbamates, I get some unexpected results.


(JChem 5.0.2 and JChem 3.2.6 both gave the same results)





select jc_Standardize('CC(C)(C)OC(=O)NC1CCCCC1', 'sep=! config:tautomerize') from dual





output = CC(C)(C)OC(O)=NC1CCCCC1


I expected the initial Smiles to be returned.





I have tried to draw the same molecule in MSketch (5.0.3) and the major tautomer is 'CC(C)(C)OC(=O)NC1CCCCC1'





Why does the Standardizer not return the major tautomer?





Thanks


Catherine

The tautomerize action of standardizer returns a canonical tautomeric form, whch is not necessarily the stable tautomer. The canonical tautomer calculation is under revision at the moment, it changed in version 5.0.3 and will probably change in the next version as well. Our developers are just working on that part of the code.





If you are standardizing your compounds for substructure searching, please do not use tautomerize and mesomerize actions, because they are intended to provide canonical molecules, but not canonical functional groups. For example, the canonical tautomer of a compound can be an enol, while the canonical tautomer of another compound is oxo.

I understand why selecting

jc_standardize(smiles, 'config:tautomerize outFormat:smiles:u') canonical,

jc_evaluate_x(smiles, 'chemTerms:dominantTautomer() outFormat:smiles:u') stable

might return different values for one structure, but if different structures return the same canonical tautomer (i.e., we think they would interconvert to the same thing), shouldn't they also give the same value of the stable, dominant tautomer?  But the following example suggests otherwise:

WITH list as (select 'O=C1N=CNC1' smi from dual union all select 'O=C1NC=NC1' from dual union all select 'Oc1c[nH]cn1' from dual) select smi smiles, jc_standardize(smi, 'config:tautomerize..aromatize outFormat:smiles:u') canonical, jc_evaluate_x(smi, 'chemTerms:dominantTautomer() outFormat:smiles:u')  stable from list;

SMILES     CANONICAL STABLE

O=C1N=CNC1 Oc1c[nH]cn1 OC1=NC=NC1 

O=C1NC=NC1 Oc1c[nH]cn1 O=C1CN=CN1 

Oc1c[nH]cn1 Oc1c[nH]cn1 Oc1cnc[nH]1 

Hi,

Yes, it can occure. Because, intention of the canonical and the stable tautomers are different. See the attached figure.

Please note that we constantly improve the canonical and the stable tautomer generators. The actual version of the tauotmer generator provides better results.

Jozsi