Coupling vs Cleavage: Elucidating the Transformation Pathways and Enhanced Ecological Risks of Nonylphenols during Chlorination

While chlorination is a cornerstone of wastewater disinfection, its potential to inadvertently transform endocrine-disrupting nonylphenols (NPs) into more hazardous products remains poorly understood. In this study, we integrated non-targeted screening with density functional theory (DFT) calculations to systematically elucidate the time-dependent transformation pathways and toxicity evolution of two representative NPs (NP36 and NP112) during chlorination. Our findings reveal a distinct, multi-stage transformation mechanism: the early stage (0–30 min) is dominated by electrophilic substitution and phenoxyl radical-mediated aromatic coupling, whereas oxidative side-chain cleavage prevails in later stages. DFT analysis confirms that electrophilic attack exhibits strong ortho-selectivity, and the spontaneous formation of phenoxyl radicals serves as the key thermodynamic driver for the coupling pathways. Quantitative structure-activity relationship (QSAR) assessment indicates that aromatic coupling products and certain chlorinated products exhibit a 1–7 orders of magnitude increase in acute/chronic toxicity compared to the parent NPs, whereas side-chain cleavage functions as the sole detoxification pathway. Notably, traditional halogenated byproducts (mono-chlorinated nonylphenol and di-chlorinated nonylphenol; MCNP/DCNP) accounted for less than 6% of the initial NPs, suggesting that highly toxic coupling products, rather than halogenated species, are the primary drivers of ecological risk. This work challenges the current monitoring paradigms focused primarily on halogenated byproducts and underscores the urgent need to incorporate high-molecular-weight coupling products into risk assessment frameworks for water treatment processes.