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+# Online reactivity
+
+:material-menu-open: **Feature list methods → Feature grouping → Online reactivity**
+
+This module searches for reaction educt-product pairs in individual samples or in control and
+reacted samples. As a result features are flagged as products or educts of a reaction defined by
+SMARTS string (similar to SMILES but better to define functional groups with flexibility). This
+annotation can later be exported in the MS2 spectra export, GNPS export, SIRIUS export, and for
+other annotation tools. These SMARTS can provide information of functional groups that need to be
+present in the actual structure to facilitate structure annotation.
+
+This module follows an online, post-column derivatization/reaction LC-MS strategy. After the LC
+separation, reactants are added before ionization and MS analysis. This means that the reaction's
+educt and product have the same retention time. They may appear in the same **reacted** sample or if
+the reaction is complete, a control sample (sample without a reactant) without a reaction is
+required.
+
+Control samples (without reaction) provide additional filtering options that the product should only
+appear in reacted samples, and the educt must appear in the control and may be present in the
+reacted sample.
+
+## Recommended citations
+
+!!! info
+
+ When using mzmine for your work, please consider citing:
+ Schmid R., Heuckeroth S., Korf A., et al. Integrative analysis of multimodal mass spectrometry data in MZmine 3, Nature Biotechnology (2023), doi:10.1038/s41587-023-01690-2.
+
+ When using this modules, please consider citing the corresponding publication(s):
+ Vitale, G.A., Xia, SN., Dührkop, K. et al. Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling. Nature Communications 16, 6911 (2025). https://www.nature.com/articles/s41467-025-61240-z
+
+---
+
+## Parameters
+
+
+
+#### Feature lists
+
+Select the feature lists to process
+
+#### Reactions file
+
+This file defines the reactions applied to specific samples. The example button provides a template
+tsv or csv table file. The file contains:
+
+- **filename_contains**: A unique ID that links a reaction to a sample
+- **reaction_name:** A free text name for the reaction
+- **delta_mz:** The m/z difference of m/z(product) - m/z(educt)
+- **educt_smarts:** The SMARTS that defines the educt of the reaction. This is the molecule targeted
+ by the reaction.
+- **reaction_smarts:** The reaction SMARTS that defines the transformation from educt to product.
+ The . defines molecule boundaries and allows the definition of multiple molecules per reaction
+ side. [SMARTS definitions.](https://www.daylight.com/dayhtml/doc/theory/theory.smarts.html)
+
+| filename_contains | reaction_name | delta_mz | educt_smarts | reaction_smarts |
+|-----------------------|---------------|----------|----------------------|--------------------------------------------------|
+| unique_id_in_filename | my_reaction | 123.45 | (\[#6]\[CX3]\(=O\)O) | (\[#6]\[CX3]\(=O\)O).(OC)>>\[#6]\[CX3]\(=O\)OC.O |
+
+#### Unique sample ID
+
+Metadata column that defines a unique sample ID. Go to Project/Metadata to load a metadata sheet and
+reload this module to select this column. The values should be a substring found in the filenames.
+Make sure to use a prefix or suffix before and after numbers otherwise id1 also matches id10. Just
+adding a simple suffix id1_ will resolve this issue.
+
+#### Reaction sample type
+
+Metadata column that defines all samples as either control or reacted. Control is unreacted and
+reacted is after applying the reaction. Go to Project/Metadata to load a metadata sheet and reload
+this module to select this column.
+
+Possible values are:
+
+- **Control**: false, educt, control
+- **Reacted**: true, product, reacted
+
+#### Only grouped features
+
+Only allow reaction relationships if the features where grouped. For example,
+by [metaCorrelate](../id_ion_networking/metacorr/metacorr.md)
+feature grouping based on retention time. The idea is that in the online reaction setup, the
+retention time should be the same for educts and products. If the educt is fully converted into
+products in the reacted samples, then consider disabling feature shape correlation to rely on
+retention time only for grouping.
+
+#### m/z tolerance
+
+The tolerance to match the reaction with potential educt and product features. The m/z tolerance is
+applied to the product m/z (important for the relative tolerance in ppm). This means a potential
+product is matched against the educt + delta_mz (from reactions file).
+
+#### Educt adducts & Product adducts
+
+Educt and product adducts define more combinations to check reactivity matches.
+This can be helpful if the ionization changes after the reaction, e.g.,
+educt ionizes as \[M+Na\]+ and product as \[M+H\]+ - this changes the delta m/z searched.
+
+---
+
+{{ git_page_authors }}
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--- a/mkdocs.yml
+++ b/mkdocs.yml
@@ -47,7 +47,7 @@ nav:
- Mass calibration: module_docs/featdet_mass_detection/mass-calibration.md
- LC-MS feature detection:
- Chromatogram builder: module_docs/lc-ms_featdet/featdet_adap_chromatogram_builder/adap-chromatogram-builder.md
- - MSn tree builder: module_docs/lc-ms_featdet/featuredet_msn_tree/msn_tree_builder.md
+ - MSn tree builder: module_docs/featuredet_msn_tree/msn_tree_builder.md
- GridMass: module_docs/lc-ms_featdet/featdet_gridmass/gridmass.md
- Targeted feature detection: module_docs/lc-ms_featdet/targeted_featdet/targeted-featdet.md
- Feature detection results: module_docs/lc-ms_featdet/featdet_results/featdet_results.md
@@ -85,6 +85,7 @@ nav:
- Correlation grouping: module_docs/id_ion_networking/metacorr/metacorr.md
- Ion Identity Networking: module_docs/id_ion_networking/iin/iin.md
- Spectral / Molecular Networking: module_docs/group_spectral_net/molecular_networking.md
+ - Online reactivity: module_docs/id_online_reactivity/online_reactivity.md
- Feature list filtering:
- Duplicate feature filter: module_docs/filter_duplicate_features/duplicate_feature_filter.md
- Feature list rows filter: module_docs/feature_list_row_filter/feature_list_rows_filter.md