init draft aromatic

[fgrunewald]

This is the initial draft of the new aromaticity algorithm following the ideas outlined here and here.

The key difference is that we are not trying to assign chemical aromaticity but rather kekulize the molecule (i.e. fixing hcount). In a nutshell, the algorithm proceeds as follows:

1. Assign a preliminary hcount to all non-hydrogen atoms. This is a bit awkward but needed for the next step, because we want to be able to deal with cases where implicit hydrogen are part of the non-aromatic atoms.
2. Remove all nodes that have a full valance, which we can only assess after implicit hydrogens have been added to non-aromatic residues.
3. Get the connected components of the resulting fragmented graph. Each component has to be a delocalized system and is potentially aromatic.
4. For each component we check if there exists a maximum matching and if that matching is perfect. If it is not perfect the delocalized system is written incorrectly and a syntax error is raised. It's like checking if we have perfect alternating single and double bonds.
   5a. If the system is cyclic we assume it to be (anti-)aromatic and give it a bond order of 1.5.
   5b. If it is not cyclic then we simply assign a bond order of 2 to the edges that constitute the perfect matching.

Some differences in behaviour to the previous version:

SMILES	VALID	AROMATIC	old	new
c1c[nH]cc1	yes	no	pass	pass
c1cNcc1	yes	no	pass	pass
c1cncc1	no	raises Error	fail (no hydrogen on N)	pass
c1cscc1	yes	no	fail	pass
c1cScc1	yes	no	pass	pass
c1cnc[nH]1	yes	no	pass	pass
c1cncN1	yes	no	pass	pass
N12ccccc1ccc2	yes	no	pass	pass
n12ccccc1ccc2	yes	no	pass	pass
c12ccccc1Ncc2	yes	no	pass	pass
c12ccccc1[nH]cc2	yes	no	pass	pass
c12ccccc1ncc2	no	raises Error	fail (no hyrdogen on N)	error
c1cscn1	yes	no	fail	pass
cccc	yes	no	fail (raises Error)	pass
OCCn2c(=N)n(CCOc1ccc(Cl)cc1Cl)c3ccccc23	yes	partly	fail ( h on aromatic n)	pass

The molecule from this blog-post mentioned in #19 is also fixed.

Overall I'd say this algorithm is more robust as it raises an Error for hard fails like c1cncc1 but is also linenet towards chemically intuative smiles like cccc.

The major problems are:

• how to deal with wildcards ? For now they are just ignored because we don't know the valency and bond order. That means [*]1[*][*]1 is not aromatic anymore.
• how to deal with charges in the intial valance assignment ? I think it should be missing = valance - bonds + charges
• how to assing aromarticity for fused rings. Currently napthalene is not aromatic, which might be fine???

[pckroon]

Many thanks! First your questions, I'll have a look at the code as well.

how to deal with wildcards ? For now they are just ignored because we don't know the valency and bond order. That means []1[][*]1 is not aromatic anymore.

Wildcard should always be able to form a double bond without inducing a charge, so they should be part of the delocalized subgraph. I'm not a hundred percent sure why [*]1[*][*]1 should be aromatic though, since it only has 3 atoms.

how to deal with charges in the initial valence assignment ? I think it should be missing = valence - bonds + charges

I need to brood on this. Can this be summarized in such a general way, or do we need to do actualy octet-rule?

how to assign aromaticity for fused rings. Currently naphthalene is not aromatic, which might be fine???

This is a problem IMO, naphthalene does show DIME.

[pckroon]

Very nice! I do think it can be cleaned up a little bit more though.
We can also draw some inspiration from https://github.com/aspuru-guzik-group/selfies/blob/master/selfies/mol_graph.py#L287

We can assume that any atom that did not specify any number of hydrogens is saturated and can be pruned from the DS. So no need to prefill the valence.
The wildcard atoms can become an issue if they result in a non-perfect matching, so maybe all wildcards that are not in a maximal matching should be removed before checking whether it's perfect.

[fgrunewald]

@pckroon small update: so naphthalene is correctly assigned (now). I had an earlier error. All systems that show DIME are identified as aromatic as far as test-cases go. Only those like Thiophene are not.

[pckroon]

Love it. Small nitpick on some code, and a doubt on the indole test

[pckroon]

Awesome work, I love it <3

[pckroon]

Could you add 2 more testcases? One with a triangle, and one that cannot be kekulized and trips the error. That should bring the coverage back up