Formation, Identification, and Occurrence of New Bromo- and Mixed Halo-Tyrosyl Dipeptides in Chloraminated Water

Abstract

Dipeptides are widely present in surface water and serve as precursors to form disinfection byproducts (DBPs) during disinfection (e.g., chloramination). Bromide (Br–) and iodide (I–) are common in many source waters, enhancing Br- and I-DBP formation. Recently Cl-, I-, and Cl-I-dipeptides were identified after chloramination of tyrosyl dipeptides in the presence of I– and were detected in authentic disinfected drinking water samples. However, the formation and occurrence of Br- and mixed halogen (Cl, Br, and/or I)-dipeptides in disinfected water have not been studied. Here we investigated the formation of halogenated dipeptides from three aromatic dipeptides, phenylalanylglycine (Phe-Gly), tyrosylalanine (Tyr-Ala), and tyrosylglycine (Tyr-Gly), under chloramination in the presence of Br– and I– at environmentally relevant levels ([Br–] and [I–], 0 and 0 μg L–1, 6 and 30 μg L–1, 30 and 30 μg L–1, 150 and 30 μg L–1, 300 and 30 μg L–1, and 900 and 30 μg L–1, respectively). For the first time, N-Br- and N,N-di-Br- as well as N-Br-N-Cl- and N-Br-3-I-tyrosyl dipeptides were identified using infusion electrospray quadrupole time-of-flight mass spectrometry. Tyrosyl dipeptides produced N-Cl-, 3-I-/3,5-di-I-, and N-Cl-3-I-tyrosyl dipeptides, while Phe-Gly formed only N-Cl-/N,N-di-Cl-Phe-Gly. To determine halogenated dipeptides in authentic water samples, we developed a new method of solid phase extraction and high-performance liquid chromatography with quadrupole ion trap mass spectrometry using reaction monitoring. 3,5-Di-I-Tyr-Ala and N-Br-Tyr-Ala were detected in treated water but not in the corresponding raw water, warranting further investigation into the occurrence of halogenated peptides in other drinking water systems.

Cytotoxicity of Halogenated Tyrosyl Compounds, an Emerging Class of Disinfection Byproducts

“…26,27 Huang and colleagues also found that free iodide or bromide can influence the formation of iodinated and brominated DP−DBPs during disinfection. 14,15 The greater cytotoxicity of the di-iodinated and dibrominated species observed here is therefore relevant to source waters that contain elevated iodide or bromide levels due to natural or anthropogenic factors such as seawater intrusion, wastewater discharge, geomorphological deposits, or hydraulic fracturing activities, 25,28−32 as the disinfection of these source waters could lead to the formation of more cytotoxic tyrosyl-DBPs.…”

“…16 These compounds are also of toxicological interest, because the presence of free iodide or bromide during treatment can induce the formation of iodinated and brominated tyrosyl DBPs. 14,15 In general, the toxicity trend among analogous DBPs is iodo-> bromo-≥ chloro-DBPs. 20,21 To better understand the human health implications related to exposure, a systematic evaluation of the cytotoxicity of halogenated tyrosyl compounds is needed.…”

“…With its two reactive sites, the amino acid tyrosine (Tyr) has been shown to be reactive to chlorination and can form highly stable reaction products, which was also observed with tyrosyl dipeptides . Halogenated tyrosyl compounds have been identified as DBPs in treated tap water − and in lettuce and spinach washed with treated water . Formation of these compounds is influenced not only by the identity of the peptides present, but also by the presence of free halogen ions, including iodide and bromide. , In the presence of iodide, 3-iodo-tyrosylalanine (3-I-Tyr-Ala) and 3,5-di-iodo-tyrosylalanine (3,5-di-I-Tyr-Ala) were identified as the predominant byproducts from chloramination of the tyrosyl dipeptide tyrosylalanine (Tyr-Ala), formed via electrophilic substitution .…”

“…Halogenated tyrosyl compounds have been identified as DBPs in treated tap water − and in lettuce and spinach washed with treated water . Formation of these compounds is influenced not only by the identity of the peptides present, but also by the presence of free halogen ions, including iodide and bromide. , In the presence of iodide, 3-iodo-tyrosylalanine (3-I-Tyr-Ala) and 3,5-di-iodo-tyrosylalanine (3,5-di-I-Tyr-Ala) were identified as the predominant byproducts from chloramination of the tyrosyl dipeptide tyrosylalanine (Tyr-Ala), formed via electrophilic substitution . Halogenated tyrosyl compounds have also been found intracellularly as a major product of protein oxidation in human cells …”

“…Some chlorinated amino acids have been found to be mutagenic in bacterial assays and can induce micronuclei formation in human cells. , 3-Chloro-tyrosine (3-Cl-Tyr) and 3,5-dichloro-tyrosine (3,5-di-Cl-Tyr) were also shown to be more cytotoxic than regulated THMs in Chinese hamster ovary (CHO) cells . These compounds are also of toxicological interest, because the presence of free iodide or bromide during treatment can induce the formation of iodinated and brominated tyrosyl DBPs. , In general, the toxicity trend among analogous DBPs is iodo- > bromo- ≥ chloro-DBPs. , To better understand the human health implications related to exposure, a systematic evaluation of the cytotoxicity of halogenated tyrosyl compounds is needed.…”