Structure confirmation, reactivity, bacterial mutagenicity and quantification of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in drinking water

Davide Ciccarelli; Ben M J Lancaster; D Christopher Braddock; Matteo Calvaresi; Miroslav Mišík; Siegfried Knasmüller; Edoardo Jun Mattioli; Francesco Zerbetto; Andrew J P White; Tim Marczylo; Timothy W Gant; Leon P Barron

doi:10.1038/s42004-024-01356-3

Structure confirmation, reactivity, bacterial mutagenicity and quantification of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in drinking water

Commun Chem. 2024 Nov 14;7(1):266. doi: 10.1038/s42004-024-01356-3.

Authors

Davide Ciccarelli^{1

2}, Ben M J Lancaster³, D Christopher Braddock³, Matteo Calvaresi⁴, Miroslav Mišík⁵, Siegfried Knasmüller⁵, Edoardo Jun Mattioli⁴, Francesco Zerbetto⁴, Andrew J P White³, Tim Marczylo^{2

6}, Timothy W Gant^{2

6}, Leon P Barron^{7

8

9}

Affiliations

¹ Environmental Research Group, MRC Centre for Environment and Health, School of Public Health, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK.
² NIHR-HPRU Chemical and Radiation Threats and Hazards, NIHR-HPRU Environmental Exposures and Health, MRC Centre for Environment and Health, School of Public Health, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK.
³ Department of Chemistry, Imperial College London, 82 Wood Lane, London, W12 0BZ, UK.
⁴ Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum - Università di Bologna, Via Francesco Selmi 2, 40126, Bologna, Italy.
⁵ Medical University of Vienna, Center for Cancer Research, Borschkegasse 8a, 1090, Vienna, Austria.
⁶ UK Health Security Agency, Harwell Science Campus, Oxon, OX11 0RQ, UK.
⁷ Environmental Research Group, MRC Centre for Environment and Health, School of Public Health, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK. [email protected].
⁸ NIHR-HPRU Chemical and Radiation Threats and Hazards, NIHR-HPRU Environmental Exposures and Health, MRC Centre for Environment and Health, School of Public Health, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK. [email protected].
⁹ UK Health Security Agency, Harwell Science Campus, Oxon, OX11 0RQ, UK. [email protected].

Abstract

The presence of two new disinfectant by-product (DBP) groups in the UK was recently shown using non-target analysis, halogenated-hydroxycyclopentenediones and halogenated-methanesulfonic acids. In this work, we confirmed the structure of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione (TBHCD), and quantified it together with dibromomethanesulfonic acid at 122 ± 34 and 326 ± 157 ng L^-1 on average in London's drinking water, respectively (n = 21). We found TBHCD to be photolabile and unstable in tap water and at alkaline pH. Furthermore, spectral and computational data for TBHCD and three other halogenated-hydroxycyclopentenediones indicated they could act as a source of radicals in water and in the body. Importantly, TBHCD was calculated to have a 14.5 kcal mol^-1 lower C-Br bond dissociation enthalpy than the N-Br bond of N-bromosuccinimide, a common radical substitution reagent used in organic synthesis. TBHCD was mutagenic in Salmonella/microsome assays using strains TA98, TA100 and TA102. This work reveals the unique features, activity and toxicity of trihalogenated hydroxycyclopent-4-ene-1,3-diones, prompting a need to more comprehensively assess their risks.