Linking Structural Features of Amisulpride and Sulpiride to Their Photoreactivity and Environmental Fate: The Role of NH ₂ Substitution in Photodegradation Behavior

Amisulpride (AMI) and sulpiride (SUL), two structurally related benzamide antipsychotics frequently detected in aquatic environments, differ in whether a primary amino group (-NH₂) is directly attached to the benzoyl ring, a minor variation that leads to striking differences in their photoreactivity and environmental fate. AMI undergoes rapid direct photodegradation (<i>t</i>_1/2 = 14.5 min at pH 8.0), whereas SUL degrades 28 times more slowly (<i>t</i>_1/2 = 407.7 min). Theoretical calculations revealed that the disparity originates from their primary photoexcitation mechanisms. AMI retains planarity and exhibits a strong π→π* transition, while torsional distortion in SUL results in a weak, partially forbidden n→π* transition, making SUL far more dependent on the photodegradation involving ^•OH, CO₃^•-, and self-sensitized ³SUL*. Experiments with NO₃^-, HCO₃^-, and Br^- demonstrated pronounced acceleration of SUL photodegradation in natural and simulated waters, confirming the key role of indirect pathways for SUL and their minimal contribution to AMI. Six AMI and four SUL transformation products (TPs) were identified exclusively from direct photodegradation, arising from sulfone cleavage, ring oxidation, and N-dealkylation. Toxicity predictions showed that SUL photodegradation leads to detoxification, whereas AMI produces multiple transformation products with higher predicted toxicity. These findings demonstrate that -NH₂ positional isomerism governs photoexcitation, indirect photoreactivity, and environmental risk.