Inconsistent tautomeric states

Dear support:

Consider the following protonation states of 3-amino 5-methyl indazol, in smiles format:

Cc2ccc3n[nH]c(N)c3c2
Cc2ccc3[nH]nc(N)c3c2

If I paste each of these compound variants one at a time into MarvinSketch (as SMILES), and then use the tautomer tool to ask for the dominator tautomer at a pH of 7.4, I get two very different answers (please refer to the enclosed picture). The dominate tautomer from the latter protonation state produces an imino form, which, by casual inspection, looks somewhat unlikely.

Naively, I would have expected both protonation states to be roughly equally likely.

Depending on how the two compounds are created (pasted from SMILES or drawn from scratch), different results can be obtained, suggesting some internal inconsistency.

I am currently using MarvinSketch 5.3.3.

Hi,

 

Thank you for reporting this bug.  The fix will be available in the 5.3.7 version in a few weeks.

 

Jozsi

Hello Jozsi:

I just tried the same two smiles strings on version 5.3.8, and I obtain the same, inconsistent results. Could you confirm if the issue has been fixed?

  - David W.

Hi,

 

Sorry , I  confused the version number. It was changed too fastly this summer. The fix will be available in  the 5.4 version which will be released in 2-3 weeks.

 

 You may  try the next method instead of the fix.

1. Firstly generate the "canonical tautomer".

2. Secondly apply the "pH" criteria for the "canonical tautomer".

 

Jozsi