Defining the molecular properties of N-nitrosodimethylamine (NDMA) precursors using computational chemistry?

Environmental Science: Water Research & Technology Pub Date: 2017-04-03 DOI: 10.1039/C7EW00068E

Abstract

N-Nitrosodimethylamine (NDMA) is a potent carcinogen and can be produced during chloramination of drinking water and wastewater. Computational chemistry methods were used for the first time to calculate molecular descriptors for 64 NDMA precursors containing a dimethylamine (DMA) moiety. Descriptors were partial charge, bond length and pKa of the DMA nitrogen and planarity of the DMA group. Precursors classified on the basis of chemical functionality showed distinct relationships between partial charge and NDMA formation. Quaternary amines and tertiary amines with the DMA bonded to -COR and -CSR groups had a combination of low NDMA formation and high partial charge. The most potent NDMA precursors are tertiary amines with an acidic hydrogen and electron-donating group α and β to the DMA respectively. They also have comparable molecular descriptors: relatively negative partial charges, low planarity values, high bond lengths and pKa values from ～8.3–10.1. A literature search identified 233 potential NDMA precursors that have never been tested experimentally. Of these chemicals 60% are therapeutics, 13% veterinary therapeutics and 10% natural products. Analysis combining qualitative assessment of chemical functionality and computational calculation of molecular descriptors successfully identified rivastigmine, a therapeutic, and conessine, a naturally occurring species, whose NDMA yields were determined experimentally to be 83.3 ± 0.5% and 42.3 ± 1.8% mol mol?1, respectively. This study defines the molecular properties associated with reactive NDMA precursors and the origin and identity of those amines which contribute to NDMA formation in drinking water.

Graphical abstract: Defining the molecular properties of N-nitrosodimethylamine (NDMA) precursors using computational chemistry
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