Mechanistic insights into the degradation of ibuprofen by hydroxyl radicals: A theoretical and toxicity study.

The oxidative degradation of ibuprofen (IBP) by •OH was investigated using density functional theory (DFT) to address key scientific gaps related to conformer-specific reactivity, site-selective reaction kinetics, and the environmental implications of degradation intermediates. Unlike previous studies that consider a single IBP structure and emphasize overall removal efficiency, this work systematically examines two stable IBP conformers (IBP-C1 and IBP-C2) to identify the most reactive configurations. Two primary mechanisms, hydrogen atom abstraction (HAA) and radical adduct formation (RAF), were explored, and corresponding rate constants were calculated using transition-state theory with Wigner tunneling corrections. The HAA pathway at the propanoic acid side-chain hydrogen (Path-5, H33 abstraction) exhibited the rate constant (k = 1.91 × 1013 M-1·s-1 for IBP-C1 and 1.51 × 1013 M-1·s-1 for IBP-C2), consistent with its lowest activation barrier and strongly exergonic ΔGR0 values. Among RAF pathways, the C5 cis addition (Path-13) was kinetically most favourable (k ≈ 6.3 × 1012 M-1·s-1). ECOSAR-based ecotoxicity assessment of IBP and its intermediates (Path-5: P5_IM1-P5_IM17; Path-13: P13_IM1-P13_IM11) revealed that several degradation products exhibit higher predicted toxicity than the parent compound, highlighting potential ecological risks associated with incomplete oxidation. These findings provide a conformer-dependent mechanistic and kinetic understanding of •OH-initiated IBP degradation, identifying key reactive sites and clarifying the environmental fate of its transformation intermediates.