Can tautomer plugin modify total formal charge of molecule?

Hi,

I have been looking at the pKa scan for a molecule, single_ligand.sdf, attached below. At pH 7.4 one species dominates over the other, with about 78% versus 22%. The 78% molecule has an imidazole ring where one nitrogen has no hydrogen atom attached and is negatively charged. The 22% molecule has a 'normal' imidazole ring where the nitrogen has a hydrogen atom attached and is neutral.

When I then look at the dominant tautomer distribution, taking into account pH effects at pH 7.4, regardless of which protonation state (the 88% or the 22% one) I choose as a starting point, I end up with the exact same tautomer distribution, where the most dominant tautomer (with 100% distribution) has the 'normal' imidazole ring.

My question is: can the tautomer plugin entirely add/remove a hydrogen atom from a structure, thus modifying the total formal charge of the molecule? If so, then would you recommend that I do not calculate the major microspecies prior to calculating the dominant tautomer distribution, as it is taken into account when selecting the option to consider pH effect?

Many thanks,

Juliette

Hi,

My question is: can the tautomer plugin entirely add/remove a hydrogen atom from a structure, thus modifying the total formal charge of the molecule? 

Yes. This is the intended behaviour of the dominant tautomer generation at an adjusted pH value.

 

If so, then would you recommend that I do not calculate the major microspecies prior to calculating the dominant tautomer distribution, as it is taken into account when selecting the option to consider pH effect?  

  Yes , you are right ,  it would be waste of time to generate the major microspecies in  preliminary calculation step.

 

Jozsi

Hi Jozsi,

Thank you for your reply, that's very helpful!

Juliette