Mechanistic Reaction Prediction via Discrete Flow Matching on Graph-Structured Electron Occupation

Reaction mechanisms describe the step-by-step transformations underlying chemical reactions and are central to reaction analysis and synthesis. Learning-based models have achieved strong performance on established mechanism-prediction benchmarks, but transferring them to unseen chemistry remains challenging. Such transfer is difficult because familiar mechanisms must be applied to unfamiliar molecular structures, and some target mechanisms may be poorly covered by the training data. To address these challenges, we introduce MechaVLM, a visual framework that combines transferable chemical representations with external mechanistic knowledge. It learns reusable visual features through multiscale chemical grounding and cross-rendering contrastive learning. For open-book prediction, MechaVLM retrieves a fixed set of precedents from 70,384 literature mechanism figures and re-reads relevant visual evidence as the molecular state evolves, directly using the figures without symbolic mechanism parsing. An atom-indexed language decoder then recursively generates executable electron edits to construct the complete mechanism. We further introduce MechBench, a challenging literature-derived benchmark with 2,184 mechanisms and 9,146 elementary steps. Across cross-dataset and literature-derived benchmarks, MechaVLM establishes strong zero-shot mechanism prediction. Its closed-book model alone improves Step/Pathway Top-1 by 12.50/13.93 percentage points on FlowER-to-ReactMech transfer, while external visual precedents unlock further gains on challenging OOD reactions. The learned representation also generalizes beyond mechanism prediction to atom mapping and reaction center prediction.

Reaction mechanisms consist of the step-by-step sequences of elementary reactions that explain chemical transformations. Learning the mechanism logic is therefore essential for enhancing the fundamental chemical intelligence of large language models (LLMs). The stepwise deduction of reaction mechanism aligns naturally with the reasoning paradigms of reasoning LLMs. However, current chemical LLMs primarily emphasize coarse-grained name reactions for product prediction and retrosynthesis, often leading to physical inconsistencies and hallucinations. In contrast, specialized small-scale generative models for mechanism inference typically suffer from restricted generalization capacity across diverse chemical spaces. To overcome these limitations, we built a novel, large-scale reasoning dataset of reaction mechanisms. Furthermore, we established the FukuyamaBench, a difficult benchmark derived from Fukuyama's Advanced Organic Reaction Mechanism book, to rigorously evaluate model performance on hierarchical mechanism reasoning. Our fine-tuned Qwen3-30B-A3B achieves 8.3% exact pathway match on FukuyamaBench Set~A, surpassing the specialized FlowER model (5.1%), demonstrating that mechanism-aware training substantially enhances chemical reasoning in language models.

Petri nets have been used to describe chemical processes such as reactions.They map well to chemistry: Places are the bonds between atoms and the free valence of each atom, a token is a unit of bond order, a transition forms or breaks a bond, the conserved quantities are the valence budgets of the atoms, and the enabling rule is the valence rule. These semantics are not guaranteed by learned models of reactions or neural networks that are built on Petri nets that use the net as a scaffold for message passing. Here, we ask what architecture remains a Petri net for every value of its weights. We find the answer in the theory, where all semantics of a net share the firing form $m^\prime=m+Cσ$, locality, as enabling reads only the inputs of a transition, and the enabling rule, and we prove that conservation forces the firing form and that non-negativity forces the enabling rule on local rate laws. This leaves free the rate law, which is the propensity of each transition to fire. We introduce Neural Petri Flow, which learns this rate law, or a readout for classification, and hard-wires the rest as parameter-free layers. On what we denote a valence net, atom mapping, reaction classification, and forward prediction become three tasks on one firing vector. Without training, the minimum firing vector maps 88.8% of the curated Golden set against 85.6% for RXNMapper, and 88.7 against 77.9% of the enzymatic reactions of EnzymeMap. On USPTO-480K, NPF trained on these firing vectors predicts 87.7% of the products and 67.4% when trained on a 1% subset of the training reactions. EC numbers of ECREACT are predicted at the third level for 90.2% of reactions, 5.6 points ahead of the best published method. With electrons as tokens, the same token game predicts 90.5% of the elementary steps of FlowER first, ahead of the published baseline, and every top-1 prediction is a valid molecule without a filter.