A transferable fragment dictionary for eco-safety and environmental risk assessment

Developing environmentally safe and sustainable chemicals is essential for maintaining the ecological integrity. Here we introduced a new molecular representation, atomic charge enhanced Fragment Dictionary (eFragD), to quantify fragment-level contributions to molecular biological effects, including acute toxicity and cyanocidal activity. Unlike conventional fragment-based approaches, eFragD incorporates density functional theory (DFT)-derived atomic charge information to enhance structural sensitivity, improving predictive specificity and interpretability. Applied to a dataset of 7,804 compounds, the framework identified 19 high-risk and 18 eco-compatible fragments, which were validated on 1,400 external chemicals, including antibiotics, new compounds and organic ligands for hybrid perovskite materials. This approach enables early-stage chemical screening for both biological safety and ecological compatibility, supporting sustainable materials design. Notably, in data-scarce scenarios, eFragD effectively prioritized low-toxicity cyanocides, demonstrating its utility in balancing environmental efficacy with long-term sustainability. This work bridges computational toxicology and sustainability science, providing a scalable framework for green chemistry, water quality protection, and evidence-based chemical regulation.