Groups containing Aryl alcohol are incorrectly deprotonated

[tushar-dm]

Molecule / groups containing phenol are incorrectly deprotonated at ph 7

e.g.
protonate_smiles("OC(C=CC1)=CC=1", ph_min=6.8, ph_max=7.4, precision=0.1)

returns:

Using dimorphite_dl V2.0.2

[jacobdurrant]

Hi @tushar-dm

Thanks for bringing this issue to my attention. This highlights one of the limitations of the dimorphite approach. A pure phenol has a pH of about 10, but depending on the decorating moieties, the pKa can change pretty drastically. For example, a compound that differs from phenol by only a single fluorine atom has a pKa that's much lower (per ChemAxon):

Since dimorphite uses a single phenol pattern to match all phenols, it has to cover situations where the pKa is much lower. We have very tentative plans to update dimorphite with more specific SMARTS patterns that will hopefully resolve this sort of thing, but I don't think we will be implementing that anytime soon, unfortunately.

Anyway, thanks for your interest in my lab's software. Much appreciated!