A cross-attentive multi-task graph learning framework for chemical reaction modeling.

motivationUnderstanding chemical reactions requires bridging fine-grained molecular edits with broader semantic context. Reaction mechanisms are determined not only by local atom-bond transformations but also by the global reaction class. However, most existing approaches treat these tasks separately or rely on external atom-mapping tools, introducing noise and limiting end-to-end learnability. We introduce MARCC (Mapping-Assisted Reaction Center and Classification), a multi-task graph neural network that jointly predicts atom mappings, reaction centers, and reaction classes within a unified architecture.

resultsMARCC integrates three key innovations: (i) a mapping-guided cross-attention mechanism that aligns reactants and products for local edit detection, (ii) a dual-graph design that explicitly reasons about bond-level transformations, and (iii) pooled product embeddings for global reaction classification. On the USPTO-50K benchmark, MARCC achieves state-of-the-art results when trained with both reactants and products, including 98.2% atom mapping accuracy, 99.1% Top-1 edit localization accuracy, and 97.2% reaction classification accuracy. Even under the products-only setting, MARCC delivers competitive performance comparable to specialized baselines. Ablation studies confirm the value of mapping-guided attention and multi-task supervision, which enhance both predictive accuracy and interpretability. By unifying atom-level alignment, local reactivity, and global classification, MARCC provides a structured and interpretable framework for reaction understanding. Beyond benchmarks, MARCC has the potential to support applications in reaction annotation, template discovery, and mechanism inference; with additional domain-specific modeling and data, it could be extended to biochemical domains such as enzyme-catalyzed transformations and metabolic pathway modeling. AVAILABILITY AND IMPLEMENTATION: The source code and implementation details are available at https://github.com/maryamastero/MARCC and archived at https://doi.org/10.5281/zenodo.18500230.