EPR detection of nitrogen-containing radicals in dimethylamine oxidation: insights into NDMA formation

Dimethylamine (DMA) is a key precursor for the carcinogenic N-nitrosodimethylamine (NDMA), yet the role of radical intermediates in DMA oxidation and N-N bond formation remains unclear. Using electron paramagnetic resonance (EPR), this study explored free radical generation in the DMA/NaClO and DMA/KMnO₄ systems, previously linked to NDMA formation. Without spin traps, three long-lived nitrogen-containing radicals were detected: dimethyl nitroxide radicals (DMNO˙), tetramethylhydrazine cation radicals (TMH˙⁺), and N,N-dimethylaminomethyl radicals (UDMHr). Their formation depends on pH, reaction time, and oxidant type and concentration. DMNO˙, formed via DMA oxygenation or hydrogen abstraction, is unstable at acidic pH and converts to N,N-dimethylhydroxylamine (DIMHA). TMH˙⁺ likely arises from tetramethylhydrazine (TMH) through single-electron transfer, followed by further reactions to produce UDMHr, a key NDMA precursor. This study proposes pathways for these radicals in DMA oxidation, offering direct EPR evidence of N-containing radicals and their potential role in NDMA formation.