Carbon, hydrogen, and nitrogen isotope fractionation associated with oxidative transformation of substituted aromatic N-alkyl amines

We investigated the mechanisms and isotope effects associated with the N-dealkylation and N-atom oxidation of substituted N-methyl- and N,N-dimethylanilines to identify isotope fractionation trends for the assessment of oxidations of aromatic N-alkyl moieties by compound-specific isotope analysis (CSIA). In laboratory batch model systems, we determined the C, H, and N isotope enrichment factors for the oxidation by MnO₂ and horseradish peroxidase (HRP), derived apparent ¹³C-, ²H-, and ¹⁵N-kinetic isotope effects (AKIEs), and characterized reaction products. The N-atom oxidation pathway leading to radical coupling products typically exhibited inverse ¹⁵N-AKIEs (up to 0.991) and only minor ¹³C- and ²H-AKIEs. Oxidative N-dealkylation, in contrast, was subject to large normal ¹³C- and ²H-AKIEs (up to 1.019 and 3.1, respectively) and small ¹⁵N-AKIEs. Subtle changes of the compound's electronic properties due to different types of aromatic and/or N-alkyl substituents resulted in changes of reaction mechanisms, rate-limiting step(s), and thus isotope fractionation trends. The complex sequence of electron and proton transfers during the oxidative transformation of substituted aromatic N-alkyl amines suggests highly compound- and mechanism-dependent isotope effects precluding extrapolations to other organic micropollutants reacting along the same degradation pathways.