Estrogenic Disruption Effects and Formation Mechanisms of Transformation Products During Photolysis of Preservative Parabens

Abstract

The pervasive presence of emerging contaminants (ECs) in environments and their associated adverse effects are underscored. Notably, the increased toxicity observed in the environmental transformation of ECs is often linked to the formation of transformation products (TPs). However, understanding the interaction and formation mechanisms contributing to increased toxicity, particularly concerning estrogenic effects, remains an unresolved challenge. To address this gap, by combining quantum chemical and molecular simulations with photochemical experiments in water, the identification and formation of TPs as well as their molecular interactions of estrogenic effect during the photochemical degradation of preservatives benzylparaben (BZP). Our results revealed the identification of three previously unknown TPs during the transformation of BZP using a non-targeted analysis. Notably, two of these novel TPs, namely oligomers BZP-o-phenol and BZP-m-phenol, exhibited higher estrogenic activities compared to the parent BZP. Their IC50 values of 0.26 and 0.50 μM were found to be lower than that of the parent BZP (6.42 μM). Furthermore, the binding free energies (ΔGbind) of the oligomers BZP-o-phenol and BZP-m-phenol (-29.71 to -23.28 kcal/mol) were lower than the parent BZP (-20.86 kcal/mol), confirming that their stronger binding affinities to the ERα-LBD. Subsequent analysis unveiled those hydrophobic residues made the most favourable contributions to ER binding, with Van der Waals interactions playing a significant role. In-depth examination of the formation mechanisms indicated that these toxic TPs primarily originated from the successive cleavage of ester bonds (O-CH2C6H5 and -COO group), followed by their combination with BZP*. In summary, this study provides valuable insights into the mechanisms underlying the formation of toxic TPs and their binding interactions with endocrine-disrupting effects. It offers a crucial framework for elucidating the toxicological patterns of ECs with similar structures.

Keywords: emerging contaminants, Parabens, Transformation Products, Toxicity mechanism, Molecular Simulation