Re-Examining the Role of Dichloramine in High-Yield N‑Nitrosodimethylamine Formation from N,N‑Dimethyl-α-arylamines Meredith E. Huang, Shiyang Huang, and Daniel L. McCurry* Astani Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, California 90089, United States * S Supporting Information ABSTRACT: N-Nitrosodimethylamine (NDMA) is a potent carcino- gen associated with chloramination of wastewater and wastewater- impacted drinking waters. Substantial effort has been expended to identify the precursors and mechanisms leading to NDMA formation. One of the major discoveries has been that molecules in the N,N- dimethyl-α-arylamine class, including the common pharmaceutical ranitidine, form NDMA in high yield during chloramination. Simultaneously, it was hypothesized that these precursors react with monochloramine, the dominant species in most chloramine mixtures, to form NDMA. This monochloramine hypothesis contradicts past mechanistic work with simple secondary amines, as well as practical experience showing that minimization of dichloramine reduces the level of NDMA formation during wastewater reuse and drinking water treatment. In this work, we address the contradiction between practical experience and model precursor studies by showing that N,N-dimethyl-α-arylamines form NDMA chiefly via reactions with dichloramine, rather than monochloramine. We experimentally demonstrate substantially higher NDMA yields from dichloramination than from monochloramination of four N,N-dimethyl-α-arylamine compounds, including ranitidine, and computationally rationalize declining NDMA yields at large dichloramine doses, which may explain past results reporting low NDMA yields from dichloramination of ranitidine. These results provide support for NDMA control strategies currently under evaluation at wastewater reuse facilities. ■ INTRODUCTION Since the discovery of high concentrations of the potent carcinogen N-nitrosodimethyalmine (NDMA) in recycled wastewater effluent, 1 considerable effort has been expended to characterize the precursors and formation mechanisms of NDMA during water treatment. 2-4 Early research identified chloramination as the key step in NDMA formation in water and wastewater 1 and postulated monochloramine (NH 2 Cl) as the key chlorine species. 5,6 Subsequent work indicated that dichloramine, a relatively minor component of total chlorine, was the critical compound leading to NDMA formation. 7 This dichloramine hypothesis has been exploited in NDMA control schemes; minimizing dichloramine formation has been successful at reducing NDMA formation during drinking water and wastewater chloramination. 8-11 In parallel to research on oxidative species involved in NDMA formation, research seeks to identify the organic precursors of NDMA. NDMA precursors are generally postulated to be organic amines, 2-4 such as dimethylamine. 5,6 Dimethylamine has been widely shown to form NDMA in ∼2% yield during chloramination [range of 0.5-3% (Table S1)] 12-17 but was determined not to be an important precursor in wastewater effluent. 12,13 Many other compounds have since been identified as NDMA precursors, including pharmaceut- icals, 18-22 quaternary amine polymers, 17,23-27 and a fungicide degradation product. 28 Particular attention has been focused on a class of structurally similar compounds, beginning with the pharmaceutical ranitidine, that form NDMA in high (≥40%) molar yields upon chloramination (Table S1). 16-20,29-31 This category of compounds has grown to include, e.g., N,N- dimethylbenzylamine, 5-(dimethylaminomethyl)furfuryl alco- hol, and methadone. 16,22,29 The common structural motif conveying high NDMA formation potential is the N,N- dimethyl-α-arylamine functional group. 16 Additionally, selected alkylamines (e.g., N,N-dimethylisopropylamine) were found to form NDMA in relatively high yields, indicating that the key property is a leaving group capable of stabilizing a positive charge (e.g., benzyl and isopropyl) bonded to a dimethylamine group. 16,32 The revolution in NDMA research caused by the discovery of high-yield NDMA precursors led to a revisitation of the mechanism of formation of NDMA. Several reports of high- yield NDMA formation from ranitidine implicated monochlor- amine (NH 2 Cl) as the reactive electrophile, 16,20,29 in contrast with previous research demonstrating NDMA formation from simple secondary amines was caused by dichloramine (NHCl 2 ) and contemporaneous evidence supporting the role of Received: December 20, 2017 Revised: January 19, 2018 Accepted: January 22, 2018 Published: January 22, 2018 Letter pubs.acs.org/journal/estlcu Cite This: Environ. Sci. Technol. Lett. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.estlett.7b00572 Environ. Sci. Technol. Lett. XXXX, XXX, XXX-XXX