Reaction Constants

All reactions and alternative reaction/reactant specifications are formatted with SMIRKS or SMARTS. If you’d like to edit or add to the libraries, you can follow my tutorial, here.

Please feel free to add directly to the following files in your forked version or open an issue and I can help in formatting SMARTS/SMIRKS strings to your needs as they can be quite finicky.

These are found at syndirella/syndirella/constants.

RXN_SMIRKS_CONSTANTS.json

This file defines the SMIRKS for reactions.

The .json structure follows this format:

  • Key (e.g., “Amidation”): The name of the reaction (with _ as spaces)

  • Value: A dictionary containing reaction metadata with the following fields:

    • smirks (string): The reaction SMIRKS pattern

      Example: "[#6:1](=[#8:2])-[#8;H1].[$([N+0&H1,N+0&H2]);!$(NC=*);!$(NS);!$(N=*);!$(N-O);!$(N-o):3]>>[#6:1](=[#8:2])-[#7X3:3]"

    • source (string): The source of the reaction

      • "manual": Manually curated reactions

      • "rxn-insight": Reactions from RXN insight paper

    • type (string): The reaction hierarchy type

      • "parent": Base reaction category

      • "child": More specific variant of a parent reaction

    • parent (string, optional): For child reactions, the name of the parent reaction

      Example: "Amidation"

Adding new reactions:

You can add new reactions to the library using the following command:

syndirella add-reaction --name "Reaction_Name" --smirks "SMIRKS_STRING" --find_parent --fp_type maccs_rxn_fp --threshold 0.2

--name: The name of the reaction.
--smirks: The SMIRKS string of the reaction.
--find_parent: Whether to find a parent reaction for the new reaction.
--fp_type: The type of fingerprint to use for the reaction.
--threshold: The threshold for the similarity score.

REACTANT_FILTER_CONSTANTS.json

This file defines options to transform reactants in specific reactions. Such as transforming a boronic acid to a boronate ester. The transformed reactant is used as an additional reactant in the library of reactants. It is used to structure inputs for rdkit.Chem.ReplaceSubstructs().

The .json structure follows this format:

  • Key (e.g., “Sp2-sp2_Suzuki_coupling”): This indicates the specific reaction type being targeted.

  • SMARTS Pattern (e.g., “[#5](-[#8])(-[#8])”): The SMARTS pattern to be modified for a reactant. Each reaction type can have multiple SMARTS patterns that describe specific substructures to look for in the reactants. These patterns are used to identify the appropriate atoms for modification.

  • Values:

    • name: Describes the action to take (e.g., “add_boronate_ester”). This is the modification to be applied when the SMARTS pattern is found.

    • to_add: Specifies the SMARTS string of the atoms to be added to the structure. For instance, a boronate ester group (“[#6]-[#6]1(-[#6])-[#8]-[#5]-[#8]-[#6]-1(-[#6])-[#6]”) might be added.

    • connecting_atom_id: Specifies the index (0-based) of the atom in to_add that will connect to the existing structure. This number corresponds to the atom’s position in the SMARTS string.

Example entry:

{
  "Sp2-sp2_Suzuki_coupling": {
    "[#5](-[#8])(-[#8])": {
      "name": "add_boronate_ester",
      "to_add": "[#6]-[#6]1(-[#6])-[#8]-[#5]-[#8]-[#6]-1(-[#6])-[#6]",
      "connecting_atom_id": 4
    },
    "[#9,#17,#53]": {
      "name": "add_bromine",
      "to_add": "[#35]",
      "connecting_atom_id": 0
    }
  }
}

ADDITIONAL_RXN_OPTIONS.json

This file specifies reactions that should be replaced by another reaction to make a new route for the pipeline. Similar to REACTANT_FILTER_CONSTANTS.json as it used to structure inputs for rdkit.Chem.ReplaceSubstructs(). But instead of adding the edited reactant to the library of reactants of one reaction, it is creating a completely new route.

The .json structure follows this format:

  • name: The reaction name that triggers for an additional route to be created with this reaction replaced (e.g., “Amide_schotten-baumann”). Must match the reaction name in the RXN_SMIRKS_CONSTANTS.json.

  • replace_with: The new reaction to replace the original reaction in a new route. This is the reaction you’re swapping in (e.g., “Amidation”).

  • reactant_smarts_to_replace: A SMARTS string of the atoms in the reactant you are directly editing for use in the new reaction.

  • reactant_id_to_replace: Specifies which reactant (by index, starting from 1) is being replaced in the original reaction SMIRKS.

  • reactant_smarts_to_replace_with: A SMARTS string specifying the reactant pattern that will replace the atoms found in reactant_smarts_to_replace.

  • replacement_connecting_atom_id: The index of the atom in the reactant_smarts_to_replace_with that connects to the rest of the reactant. The index is 0-based, meaning it refers to the atom index in SMARTS minus 1.

Example entry:

{
    "name": "Amide_schotten-baumann",
    "replace_with": "Amidation",
    "reactant_smarts_to_replace": "[#6X3;!$(C-N):1](=[OX1:2])-[#17,#9,#35:3]",
    "reactant_id_to_replace": 2,
    "reactant_smarts_to_replace_with": "[#6X3;!$(C-N):1](=[OX1:2])-[#8;H1:3]",
    "replacement_connecting_atom_id": 0
}

Note

To specify your own options, you can follow the tutorial syndirella/examples/fairydust/configure_fairydust.ipynb. Additionally, there are more examples seen in syndirella/examples/fairydust/additional_rxn_options_examples