HI Jan,
That is certainly a bug. It'd be good to report in github (or I can do if
if you don't have a github account).
This may not be trivial to fix but a workaround is to use the RDKit's
ChemicalReaction functionality (which tends to be more robust when it comes
to chirality):
In [31]: rxn = AllChem.ReactionFromSmarts('[NX2;H0:1]>>[*H+:1]')
In [32]: rxn
Out[32]: <rdkit.Chem.rdChemReactions.ChemicalReaction at 0x10bc6df80>
In [33]: ps = rxn.RunReactants((Chem.MolFromSmiles('C[C@
]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OCC1(F)F'),))
In [34]: len(ps)
Out[34]: 1
In [35]: Chem.MolToSmiles(ps[0][0],isomericSmiles=True)
Out[35]: 'C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)[NH+]=C(N)OCC1(F)F'
You could even use this to simplify things a bit and combine two of your
protonation patterns into one:
In [36]: rxn = AllChem.ReactionFromSmarts('[#7X2;H0:1]>>[*H+:1]') # <-
matches aromatic and aliphatic N
In [37]: ps = rxn.RunReactants((Chem.MolFromSmiles('C[C@
]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OCC1(F)F'),))
In [38]: len(ps)
Out[38]: 2
In [39]: [Chem.MolToSmiles(x[0],isomericSmiles=True) for x in ps]
Out[39]:
['C[C@]1(c2cc(NC(=O)c3ccc(C#N)c[nH+]3)ccc2F)N=C(N)OCC1(F)F',
'C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)[NH+]=C(N)OCC1(F)F']
Best,
-greg
On Sat, May 27, 2017 at 3:11 PM, Jan Halborg Jensen <[email protected]>
wrote:
>
>
> The code below protonates select nitrogen atoms using ReplaceSubstructs
> but in some cases the chirality is changed, despite the fact that I
> used MolToSmiles(xx,isomericSmiles=True)
>
> Any help appreciated
>
>
> Output
>
> C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OCC1(F)F [NX2;H0] [NH+] C[C@
> @]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)[NH+]=C(N)OCC1(F)F
>
> C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OCC1(F)F [nX2;H0] [NH+] C[C@
> ]1(c2cc(NC(=O)c3ccc(C#N)c[nH+]3)ccc2F)N=C(N)OCC1(F)F
>
>
> code:
>
> from rdkit import Chem
>
> from rdkit.Chem import AllChem
>
>
> smartsref = ( ('[NX2;H1]','[NH2+]'),
>
> ('[NX2;H0]','[NH+]'),
>
> ('[nX2;H0]','[NH+]'))
>
>
>
> smiles = "C[C@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)N=C(N)OCC1(F)F"
>
> m = Chem.MolFromSmiles(smiles)
>
>
> for (smarts1, smiles2) in smartsref:
>
> patt1 = Chem.MolFromSmarts(smarts1)
>
> patt2 = Chem.MolFromSmiles(smiles2)
>
> if(m.HasSubstructMatch(patt1)):
>
> newmol = AllChem.ReplaceSubstructs(m, patt1, patt2)
>
> for ion in newmol:
>
> ion = Chem.MolToSmiles(ion,isomericSmiles=True)
>
> print smiles,smarts1,smiles2,ion
>
> ------------------------------------------------------------
> ------------------
> Check out the vibrant tech community on one of the world's most
> engaging tech sites, Slashdot.org! http://sdm.link/slashdot
> _______________________________________________
> Rdkit-discuss mailing list
> [email protected]
> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>
>
------------------------------------------------------------------------------
Check out the vibrant tech community on one of the world's most
engaging tech sites, Slashdot.org! http://sdm.link/slashdot
_______________________________________________
Rdkit-discuss mailing list
[email protected]
https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
