Recently many studies have investigated the formation of N-nitrosodimethylamine (NDMA) from chloramination of dimethylamine (DMA) and many tertiary amines. Nonetheless, there is uncertainty about why specific tertiary amines are far more potent precursors than DMA. To investigate this, computational chemistry was used to generate a range of molecular descriptors for 52 known NDMA precursors. This included calculating partial charge, bond angle and bond length of the DMA nitrogen using Guassian 09 software and pKa values using Jaguar by Schr�dinger. The six most reactive NDMA precursors all have the DMA moiety connected via an alkyl group to an R group. DMA had the lowest partial charge of the investigated precursors, at -0.761. The five most reactive precursors - N,N-dimethylthiophene-2-methylamine, 5-(dimethylaminomethyl) furfuryl alcohol, ranitidine, N,N-dimethylbenzylamine and N,N-dimethylisopropylamine - had partial charge values between -0.263 and -0.503, while the mean partial charge across all compounds was -0.357. Furthermore, the five most reactive NDMA precursors were among those with lowest bond angle and the highest pKa values. Overall these results indicate that reactive NDMA precursors can be defined as follows: a DMA group linked by an alkyl to an R group, plus a relatively high partial charge, low bond angle and high pKa on the DMA nitrogen. Nonetheless, strong correlations between these molecular properties and NDMA formation do not exist; rather, a subtle interplay of multiple variables impact upon NDMA formation.

Identification of key molecular properties of reactive NDMA precursors using computational chemistry

248th National Meeting (2014)

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