Quantum Chemical Insights Into Glycine-Mediated Stepwise Transformation of Halobenzoquinones

Halobenzoquinones (HBQs) are emerging toxic disinfection byproducts widely present in drinking water. Although their reactions with amino acids have been reported, the detailed stepwise mechanisms remain unclear. Herein, density functional theory (DFT) was employed to systematically explore the transformation of HBQs by the anion of glycine (Gly^-), the dominant species at environmental pH. Quantitative thermodynamic and kinetic parameters were obtained for the complete transformation pathway from parent HBQs to poly-Gly-derivatized products. Two major pathways, 1,4-addition (Michael addition) and S_N2 substitution, were identified. 1,4-Addition dominates the initial reaction for mono-, di-, and trihalogenated HBQs, while S_N2 is crucial for perhalogenated HBQs. Water exerts a dual catalytic effect on key proton-transfer steps. A regioselectivity rule was established, with the para-carbon showing the highest reactivity toward subsequent nucleophilic attack, rationalized by the lowest unoccupied molecular orbital (LUMO) distributions and steric effects. Condensed Fukui functions alone are insufficient for regioselectivity prediction. This work provides molecular-level insights into the transformation and detoxification of HBQs by Gly^-, supporting their mass spectrometric identification and the design of amino acid-based water treatment strategies.