[Apologies, resending, as my previous reply did not go to rdkit; added some more info, too].
Thank you, James. My mistake was to think that, as RGroupDecompose() is somehow able to tell that molecules with this literal substructure in my set (unsubstituted N): [cid:image004.png@01D95D5E.053F3E00] match the original core I used: [cid:image005.png@01D95D5E.053F3E00] it would then stick to the core I specified for the RGroup decomposition, not create its tautomer with different R group labels on it, to match the target molecule's pattern rather than the core pattern. But OK, I imagine there's a reason for this. I tried specifying core_mol with R labels on: [cid:image006.png@01D95D5E.053F3E00] --> then all the molecules with the alternative tautomeric form, even when N is unsubstituted, do not match :/ In practice, I think I must convert all N-unsubstituted molecules to the tautomeric form I want, before running RGroupDecompose(). I tried CanonicalTautomer(), and it does not do that consistently; actually, it converts more often the desired tautomer (NH attached to the benzene ring) into the other one. Probably need to do this via a reaction. Thanks again for your input. From: James Wallace <james.wall...@evotec.com<mailto:james.wall...@evotec.com>> Sent: 22 March 2023 14:20 To: Giovanni Tricarico <giovanni.tricar...@glpg.com<mailto:giovanni.tricar...@glpg.com>> Subject: RE: invalid core SMILES returned by RGroupDecompose You don't often get email from james.wall...@evotec.com<mailto:james.wall...@evotec.com>. Learn why this is important<https://aka.ms/LearnAboutSenderIdentification> I've found some similar behaviour with respect to the tautomer, but when part of my query molecule is a bridged ring. In that case, instead of matching the structure as presented, it matches the bridged ring as a whole, as well as matching smaller rings represented by the bridge. Being able to force a 'complete' match so to speak will help here. As for your core, I've experienced this before where the aromaticity check seems to fail around the presence of [nH] in that kind of structure confusing the Kekulize/dekekulize code. All I could do to work around it was to build the molecule with the added option sanitize=False, so: mol = Chem.MolFromSmiles("[nH]1c2c([*:5])c([*:6])c([*:7])c([*:1])c2c([*:2])n1[*:3]", sanitize=False) But that's not ideal. From: Giovanni Tricarico <giovanni.tricar...@glpg.com<mailto:giovanni.tricar...@glpg.com>> Sent: 22 March 2023 10:04 To: Rdkit-discuss@lists.sourceforge.net<mailto:Rdkit-discuss@lists.sourceforge.net> Subject: [Rdkit-discuss] invalid core SMILES returned by RGroupDecompose ALERT : This message originated outside of Evotec's network. BE CAUTIOUS before clicking any link or attachment. Hello, I tried out RGroupDecompose on a set of indazoles, using "c1ccc2[nH]ncc2c1" as core molecule. Most of them gave a valid core SMILES: n1c([*:2])c2c([*:1])c([*:7])c([*:6])c([*:5])c2n1[*:4] However, some gave this core SMILES: [nH]1c2c([*:5])c([*:6])c([*:7])c([*:1])c2c([*:2])n1[*:3] which rdkit itself then refuses to convert to a molecule (other software like Dotmatics Vortex does instead (?)). [cid:image007.png@01D95D5E.053F3E00] Any idea what may be going wrong? I noticed that the tautomeric form of the indazole ring is different in the molecules that originated the 'wrong' core, in particular the H (or other substituent) is on the nitrogen atom that is not attached to the benzene ring. [In fact, that also raises the question of why a tautomer of the original core was matched by RGroupDecompose, and how one would instead force the matching of the chosen tautomer only]. 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