Filtering building blocks containing alkyl bromines and attach with R-group in core structure

Hi,

I am trying to filter the building blocks(bb) which contains only alkyl bromines not aromatic. Next use these number of bb to attach to the specific R-group of the core compound.

I have used SDF Reader to read both bb and core molecules >RDkit From Molecules-> RDKit substructure filter used smiles of br followed by RDKit Functional group. I would appreciate if you can suggest the steps for bb filtration and attaching to R-group.

Thanks,
RJ

Welcome to the forum @rajiv.

Can you be more specific about what you’re trying to accomplish, what you’ve done so far, and what you’re having trouble with?

It seems to me that the RDKit Functional Group Filter will allow you to differentiate between molecules that contain aliphatic vs aromatic bromines.

The Examples Server has workflows that use RDKit to carry out reactions. Have you looked at those?

1 Like

Thanks @elsamuel

Actually I did followed the Example server and was able to filter the building blocks with RDKit Functional Group Filter. However I am not able to attach these filtered fragments to the core molecule.

First I would like to get aliphatic bromines, next attach these fragments(Br as attaching point, by removing br) to the R-group of my core structure.

It should be something like this;

BrC1CC1 (building blocks) attach to OC(C([R])=O)C1=CC=CC=C1 and get OC(C(CC1CC1)=O)C2=CC=CC=C2

Based solely on what you’ve said here, I think the RDKit One-Component Reaction node is what you want.

You’ll need to create a SMARTS string that encodes the reaction you want to do. I use this SMARTS viewer to help with the process.

BrC1CC1 (building blocks) attach to OC(C([R])=O)C1=CC=CC=C1 and get OC(C(CC1CC1)=O)C2=CC=CC=C2

It seems to me that this reaction has an extra carbon in it. Maybe this should be double-checked.

I’ve uploaded an example workflow here:

1 Like

Hi @elsamuel

What I am really looking here as follows; Br containing bb attach to R-group in the core structure. Your suggestions could work with rxn within the bb, but I need rxn between R-group of core and bb. Hope my questions is clear here! Also, I wonder how do we make the SMART rxn scheme for this joining? Thanks

rxn

Your suggestions could work with rxn within the bb, but I need rxn between R-group of core and bb.

I’m afraid I don’t see the distinction you’re trying to make.

The workflow I shared takes the building blocks and substitutes the Br with the core. If you’re reacting each building block with the same core, then this approach works fine and gives the desired results. What exactly is the issue?

Also, I wonder how do we make the SMART rxn scheme for this joining?

I don’t think I understand what you’re asking here. I shared the link to the SMARTS documentation in my last post. It shows what these strings look like. If you’re familiar with SMILES then SMARTS is similar.

1 Like

Hi @elsamuel

Can you show me how RDKit One-Component Reaction node works for this? Attaching two fragments is more like two component reaction? rxn = AllChem.ReactionFromSmarts("[Br][:1].[R][:2]>>[:1][:2]")?

I tried something like below in RDKit One-Component Reaction SMARTS but didn’t works for me as it shown painting failed for error in product"
[#6:1][Br:2] >> [#6]-[#6]-#6:7-#6:6-[#6:9]-1=[#6:10]-[#6:11]=[#6:12]-[#6:13]=[#6:14]-1

Please share your steps you have followed! Thanks

Can you show me how RDKit One-Component Reaction node works for this?

I don’t quite understand what you’re asking for. The workflow I uploaded should have an RDKit One Component reaction node that carries out this reaction. Does it work when you download and execute the workflow? Have you looked at the node configuration?

Attaching two fragments is more like two component reaction?

From my point of view (and based solely on what you’ve posted so far) this is a simple one-component reaction: for every building block, you’re substituting the Br with the same chemical entity which you call the “core”.

If you’d like a more complicated approach, you could use the two component reaction node.

image

I’ve updated the workflow that I previously uploaded to include this. Download it and look at the molecule tables and the reaction node configurations to see how they work.

I tried something like below in RDKit One-Component Reaction SMARTS but didn’t works for me as it shown painting failed for error in product"
[#6:1][Br:2] >> [#6]-[#6]-#6:7-#6:6-[#6:9]-1=[#6:10]-[#6:11]=[#6:12]-[#6:13]=[#6:14]-1

Do you have any experience with SMILES or SMARTS? Just by looking at it you should be able to tell that this product is not a valid SMARTS string. Where did you get it from?

There really aren’t any detailed steps that I can share. I created SMARTS for the reactants and the products (using a combination of intuition, ChemDraw, and the SMARTS tool I linked to earlier), then tried to assemble a reaction query that made sense. This type of work requires a lot of reading along with trial and error.

1 Like

Many thanks @elsamuel

The SMARTS were copied from Marvin. I did used SMART plus and was having same issue.
The example workflow you provided works fine by reading the molecules from Table creator. However if I read bb from SD Reader->RDKit From Molecules → RDKit one component reaction gets “painting failed for”.

Can you share that sd file?
An alternative would be to share a workflow with the SD reader already executed.

Attached workflow with SD file

KNIME_example_one-component.knwf (9.6 KB)

Had chance to look the file? It doesnt work with SDF

The SDF reader is pointing to an sd file on your machine.

There are 3 ways I think you can get around this:

  1. Change the extension of the sd file to txt and upload it here. If it’s a large file, then we only need the few few entries.
  2. Execute the node on your end then export the workflow without resetting it. That way when you upload the workflow here the data will travel with it.
  3. Upload the SD file and workflow to your KNIME hub account and share the link here

ChemBridge.txt (1.6 MB)

Attached example SDF. I tried different sdf but it gets same error;

I think it’s just a representation issue. If you choose a different render then you see that the molecules are there:

image

image

For the RDKit rendering, if you generate new coordinates for the molecules in the product column, everything works fine:

image
image
image

1 Like

All works fine. Thanks.

Just wondering how to get the compound name in product table? Final product table doesn’t have initial fragments name!

@elsamuel Any thoughts on my previous post?

What are you asking for specifically?

Do you want a column that contains the name of the building block that went into the reaction for that row? If so, then you’ll need to join the output of RDKit reaction node with the output from the initial SD file. If you generate a counter on the SD file table, you can do an inner join on the Counter column and the Reactant Sequence Index, then retain whichever “name” column you want from the SD table

Do you want IUPAC names of the final compounds? Unless you purchase a license for the ChemAxon nodes, there’s no way to generate IUPAC names from chemical structures.

@elsamuel counter & join works! Thanks

1 Like

Can you mark this as solved and create a new post?

1 Like