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Chlor(am)ination of iopamidol: Kinetics, pathways and disinfection by-products formation
Accepted Manuscript Chlor(am)ination of iopamidol: Kinetics, pathways and disinfection by-products formation Fu-Xiang Tian, Bin Xu, Yi-Li Lin, Chen-Yan Hu, Tian-Yang Zhang, Sheng-Ji Xia, WenHai Chu, Nai-Yun Gao PII:
S0045-6535(17)30914-1
DOI:
10.1016/j.chemosphere.2017.06.012
Reference:
CHEM 19405
To appear in:
ECSN
Received Date: 23 February 2017 Revised Date:
22 May 2017
Accepted Date: 4 June 2017
Please cite this article as: Tian, F.-X., Xu, B., Lin, Y.-L., Hu, C.-Y., Zhang, T.-Y., Xia, S.-J., Chu, W.-H., Gao, N.-Y., Chlor(am)ination of iopamidol: Kinetics, pathways and disinfection by-products formation, Chemosphere (2017), doi: 10.1016/j.chemosphere.2017.06.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Chlor(am)ination of iopamidol: Kinetics, pathways
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and disinfection by-products formation
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Fu-Xiang Tian1, Bin Xu1*, Yi-Li Lin2, Chen-Yan Hu3, Tian-Yang Zhang1, Sheng-Ji
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Xia1, Wen-Hai Chu1, Nai-Yun Gao1
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1. State Key Laboratory of Pollution Control and Resource Reuse, Institute of
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Disinfection By-product Control in Water Treatment, College of Environmental
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Science and Engineering, Tongji University, Shanghai 200092; P. R. China
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2. Department of Safety, Health and Environmental Engineering, National Kaohsiung
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First University of Science and Technology, Kaohsiung 824, Taiwan, R.O.C.
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3. College of Environmental and Chemical Engineering, Shanghai University of
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Electric Power, Shanghai 200090; P. R. China
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*Corresponding author: Bin Xu
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Email: [email protected]
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Phone: +86-13918493316
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Abstract The degradation kinetics, pathways and disinfection by-products (DBPs)
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formation of iopamidol by chlorine and chloramines were investigated in this paper.
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The chlorination kinetics can be well described by a second-order model. The
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apparent second-order rate constants of iopamidol chlorination significantly increased
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with solution pH. The rate constants of iopamidol with HOCl and OCl- were
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calculated as 1.66±0.094×10-3 M-1 s-1 and 0.446±0.022 M-1 s-1, respectively. However,
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the chloramination of iopamidol fitted well with third-order kinetics and the
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maximum of the apparent rate constant occurred at pH 7. It was inferred that the free
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chlorine (i.e., HOCl and OCl-) can react with iopamidol while the combined chlorine
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species (i.e., NH2Cl and NHCl2) were not reactive with iopamidol. The main
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intermediates during chlorination or chloramination of iopamidol were identified
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using ultra performance liquid chromatography - electrospray ionization-mass
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spectrometry (UPLC-ESI-MS), and the destruction pathways including stepwise
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deiodination, hydroxylation as well as chlorination were then proposed. The regular
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and iodinated DBPs formed during chlorination and chloramination of iopamidol
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were measured. It was found that iodine conversion from iopamidol to toxic iodinated
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DBPs distinctly increased during chloramination. The results also indicated that
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although chloramines were much less reactive than chlorine toward iopamidol, they
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led to the formation of much more toxic iodinated DBPs, especially CHI3.
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Keywords:
iopamidol;
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by-products (DBPs).
kinetics;
chlorination;
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chloramination;
disinfection
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1. Introduction Iodinated X-ray contrast media (ICM) have been widely used for imaging of
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organs or blood vessels during diagnostic tests (Perez et al., 2006; Duirk et al., 2011).
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Generally, they are administered at high daily doses in human medicine and then be
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excreted without much metabolization (Schulz et al., 2008). Therefore, ICM have
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been frequently detected in wastewater and surface waters at elevated concentrations
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(sometimes more than 10 µg L-1) (Perez et al., 2006; Schulz et al., 2008; Sugihara et
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al., 2013). As one type of emerging waterborne pollutants, ICM have drawn more and
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more concerns recently due to their extremely stable structure and evidenced
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conversion to highly toxic iodinated disinfection by-products (DBPs) (Perez et al.,
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2006; Jeong et al., 2010; Duirk et al., 2011; Sugihara et al., 2013; Tian et al., 2014).
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Iopamidol is the most frequently detected ICM in waters at concentrations of several
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µg L-1 (Ternes and Hirsch, 2000; Perez et al., 2006; Duirk et al., 2011). Chlorinated
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and chloraminated source waters containing iopamidol were reported to be genotoxic
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and cytotoxic to mammalian cells (Plewa et al., 2004; Richardson et al., 2008). Duirk
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et al. have demonstrated that ICM, especially iopamidol, act as an important organic
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iodine source in the formation of iodinated DBPs (Duirk et al., 2011), which are much
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more toxic than the regular DBPs such as trihalomethanes (THMs) and haloacetic
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acids (Bichsel and von Gunten, 2000; Smith et al., 2010; Richardson et al., 2012).
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Moreover, the degradation of iopamidol could lead to the formation of intermediates
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that are partially or completely iodinated, chlorinated or hydroxylated on the aromatic
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ring (Tian et al., 2014; Wendel et al., 2014). The iodinated aromatic DBPs have also
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been reported to present significantly higher developmental toxicity and growth
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inhibition than aliphatic iodinated DBPs and regulated DBPs (Yang and Zhang, 2013;
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Pan et al., 2016).
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ACCEPTED MANUSCRIPT Chlorine is the most common oxidant and disinfectant used in water treatment
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plants nowadays (Bull et al., 1995). Therefore, extensive studies have investigated the
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chlorination of organic compounds such as endocrine disruptors (Deborde et al., 2004;
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Gallard et al., 2004), antibacterials (Dodd and Huang, 2007), herbicides (Duirk and
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Collette, 2006; Acero et al., 2007; Xu et al., 2011; Zhang et al., 2013) and
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pharmaceuticals (Acero et al., 2010). However, the formation of undesirable DBPs
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during chlorination has received high concerns because of their high toxicity and
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carcinogenicity (Hu et al., 2002; Richardson et al., 2012). Chloramines are therefore
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adopted as a secondary disinfectant to reduce DBP formation in drinking water
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because chloramines are weaker disinfectants and can produce much less DBPs
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compared to chlorine (Hua and Reckhow, 2007). Chloramination of many organic
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compounds have been reported, such as organophosphorus pesticides (Duirk et al.,
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2010), nitrogenous organic compounds (Yang et al., 2010), algal organic matter (Fang
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et al., 2010), herbicide (Xu et al., 2012), and oxytetracycline (Bi et al., 2013).,.
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However, the formation of iodinated DBPs has also been reported during
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chloramination at levels higher than those during chlorination. Both chlorine and
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chloramines can oxidize iodide to hypoiodois acid (HOI). However, the subsequent
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reactions to form iodate are much faster than reactions those to form iodinated DBPs
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during chlorination, while the corresponding reactions to form iodite and iodate are
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much slower than those to form iodinated DBPs during chloramination (Bichsel and
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von Gunten, 1999; 2000. Richardson et al., 2012).
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Due to their structure stability, the degradation kinetics and pathways of ICM
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during chlorination and chloramination have not been fully explored. As the most
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reported organic iodine contributors to iodinated DBPs (Duirk et al., 2011; Tian et al.,
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2014; Wang et al., 2014; Ye et al., 2014) and persistent organic pollutants (Doll and
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al., 2013), ICM, especially iopamidol, are beginning to gain more and more attention
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in water treatment processes. However, limited studies have focused on the
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degradation of iopamidol during common oxidation process (Tian et al., 2014; Wang
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et al., 2014; Wendel et al., 2014). Wendel et al. (2014) investigated the reaction
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kinetics, iodine fate, reaction pathways as well as mammalian cell toxicology of
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iopamidol during chlorination, but the chloramination kinetics and DBPs, especially
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iodinated DBPs formation were not involved. Therefore, it is of great practical
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significance to investigate and understand the mechanisms and DBPs formation of
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iopamidol during chlorination and chloramination.
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The objectives of this study were (1) to investigate the degradation kinetics and
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the effect of pH during chlorination and chloramination of iopamidol and (2) to
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elucidate the degradation pathways and the formation of regular and iodinated DBPs
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during chlorination and chloramination of iopamidol. This study aimed to shed light
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on the possible transformation mechanisms of ICM to toxic iodinated DBPs by
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oxidants in water treatment.
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2. Materials and methods
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2.1. Chemicals
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All chemicals were at least of analytical grade and used without further
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purification. The calibration standards, internal standards, surrogate standards for
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volatile DBPs (including THMs with 3 hydrogen atoms being replaced by chlorine
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and/or bromine (THM4), vinyl chloride (VC), haloketones (HKs), haloacetonitriles
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(HANs) and chloropicrin (CP)), EPA 552.2 haloacetic acids mix, CHI3 (99%),
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iodoacetic acid (≥ 99.0%) standards, sodium hypochlorite (NaOCl) solution (available
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ACCEPTED MANUSCRIPT chlorine 4.00-4.99%), ammonium acetate (≥98%), NaOH (≥98%), KH2PO4 (≥99.0%),
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Na2CO3 (≥99.0%), and NaHCO3 (≥99.0%) were purchased from Sigma-Aldrich (St.
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Louis, MO, USA). The CHClI2 and CHCl2I standards were obtained from CanSyn
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Chemical Corp. (Canada). Iopamidol (99.6%) was obtained from U.S.Pharmacopeia.
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Formic acid solution (49-51%) was purchased from Fluka (St. Louis, MO, USA).
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Triiodoacetic acid (90%) standard solution was obtained from Toronto Research
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Chemicals Inc. (Canada). Methyl tert-butyl ether (MtBE) and acetonitrile were
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obtained from J.T. Baker (USA). Analytical grade reagents including Na2S2O3,
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Na2SO4 and H2SO4 were purchased from Sinopharm Chemical Reagent Co., Ltd.
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(Shanghai, China). All solutions were prepared with ultra-pure water produced by a
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Milli-Q water purification system (Millipore, USA).
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The monochloramine (NH2Cl) solution was freshly prepared by mixing NH4Cl
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and NaOCl solutions at a Cl2/N molar ratio of 0.8 at pH 8.5 (Mitch and Sedlak, 2002).
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2.2. Experimental procedures
Chlorination and chloramination of iopamidol were carried out in a batch reactor
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fixed in a thermostatic culture oscillator at controlled temperature of 25±1 oC. The
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batch reactor was a 250 mL bottle equipped with a dispenser. Experiments were
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conducted in duplicate under pseudo-first-order conditions, while the dosage of
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oxidant was at least 10 times higher than that of iopamidol. In kinetic experiments, the
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Cl2 concentrations were controlled at 50, 100, 200, 500 and 1000 µM while the
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NH2Cl concentrations were 50, 100, 25 and 1000 µM, respectively. Experiments were
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initiated by adding Cl2 or NH2Cl stock solution to the reactor containing iopamidol
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with concentration of 5 µM. The solution was buffered at pH 5 - 9 using 10 mM
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phosphate (for pH 5-8) or carbonate (for pH 9) buffer, and the pH was adjusted with
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ACCEPTED MANUSCRIPT small volume of 0.01, 0.1 or 1 M H2SO4 and/or NaOH. At different reaction time,
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1 mL of solution was rapidly transferred into an ultra performance liquid
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chromatography (UPLC) vial containing Na2SO3 solution (20 mM) at 1.2 times of
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oxidant concentration to quench the reaction, and then the samples were analyzed
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using UPLC or ultra performance liquid chromatography-electrospray ionization-mass
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spectrometry (UPLC-ESI-MS) as soon as possible.
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The experiments of DBPs formation were conducted in triplicate under
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headspace-free conditions in 40-mL glass screw-cap amber vials with PTFE-lined
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septa in dark at 25 ±1 o) in a thermostatic biochemical incubator. The concentrations
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of iopamidol and chlor(am)ine were 10 and 100 µM, respectively. At the scheduled
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time of 7 d, the reaction was quenched using NH4Cl (for regular DBPs) or Na2SO3
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(for iodinated DBPs) at 1.2 times of the oxidant concentration, and the samples were
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then extracted for analysis as soon as possible (Lin et al., 2014).
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The experiments for the identifying of intermediates during iopamidol
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chlor(am)ination were conducted at initial iopamidol concentration of 25 µM for
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higher analytical resolution. The solutions were buffered using 10 mM phosphate and
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the pH was adjusted with H2SO4 and/or NaOH. After dosed with 250 µM
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chlor(am)ine, the samples were collected and quenched with Na2SO3 solution at the
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scheduled time of 0, 2, 4, 8, 12 and 24 h for chlorination, and 0, 24, 48, 96, 120, 144
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and 168 h for chloramination, respectively. Finally, with no further extraction steps,
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the samples were directly analyzed using UPLC-ESI-MS immediately.
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2.3. Analytical methods
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Iopamidol was analyzed using UPLC (Waters, USA) equipped with a XTerra®
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MS C18 column (4.6 mm×250 mm i.d., 5 µm film thickness, Waters, USA) and an
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UV detector at the wavelength 242 nm. The mobile phase was consisted of 10%/90%
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(v/v) acetonitrile and Milli-Q water at a flow rate of 0.80 mL min-1. The injection
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volume was 10 µL and the detection limit of iopamidol was 6.4×10-3 µM (5 µg L-1). The pH measurements were carried out with a regularly calibrated pH meter
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(FE20-FiveEasy, Mettler Toledo, Switzerland) using standard buffer solutions
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(Mettler Toledo, pH = 4.01, 7.00 and 9.21). The concentrations of Cl2 and NH2Cl
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were measured using the N, N-diethyl-p-phenylenediamine (DPD) colorimetric
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method (APHA, 1998).
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Methods for quantifying regular and iodinated DBPs were developed by
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modifying the USEPA Method 551.1 (Munch and Hautman, 1995) and 552.2
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(Hodgeson et al., 1995). Samples were extracted with MtBE, and the extracts were
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analyzed using a gas chromatograph (GC-2010, Shimadzu, Japan) equipped with an
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electron capture detector (ECD) and a HP-5 capillary column (30 m×0.25 mm i.d.,
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0.25 µm film thickness, J&W, USA). The injector and detector temperatures were 200
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and 290 οC, respectively, and the flow rate of the nitrogen carrier gas was 30 mL min-1
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with pressure of 69.8 kPa. The temperature program for the analysis of regular DBPs
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was as follows: hold at 37 οC for 10 min, ramp to 50 οC at rate of 5 οC min-1 and hold
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for 5 min, and finally ramp to 260 οC at rate of 15 οC min-1 and hold for 10 min. The
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temperature program for the analysis of iodinated DBPs was as follows: hold at 40 οC
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for 10 min and then ramp to 260 οC at rate of 15 οC min-1 and hold for 10 min.
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The analysis of intermediates during iopamidol chlor(am)nation was carried out
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using a UPLC-ESI-MS system consisted of an Accela U-HPLC system, a TSQ
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Quantum mass spectrometer (ESI source, Thermo Scientific Inc., USA) and an
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XTerra® MS C18 column (250 mm×2.1 mm, i.d., 5 µm film thickness, Waters, USA).
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Acetonitrile and 1% formic acid solution (10%/90%, v/v) were used as the mobile
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were as follows: spray voltage 4.0 kV, capillary temperature 350 oC, sheath gas
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pressure 50 (arbitrary units), and auxiliary gas pressure 45 (arbitrary units). The MS
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chromatograms were obtained both in total ion current (TIC) mode using full scans
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(m/z 200-900) for mass spectra acquisition and the selected ion monitoring (SIM)
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mode.
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3. Results and discussion
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3.1. Chlorination of iopamidol
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3.1.1. Chlorination kinetics
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The kinetics for the chlorination of organic compounds such as phenols,
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bisphenol A, chlortoluron, have been developed to be a second-order model,
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first-order in chlorine and first-order in compound concentrations (Gallard and von
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Gunten, 2002; Gallard et al., 2004; Xu et al., 2011). Based on this conclusion, the
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relationship of ln (C0/Ct) to the reaction time (t) with different initial chlorine dosages
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was analogously fitted and shown in Fig. 1, where C0 and Ct are the concentrations of
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iopamidol (M)at reaction time of t = 0 and t = t, respectively.
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The good linear fit (R2>0.994) of experimental data was indicative of the
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pseudo-first order kinetic for iopamidol chlorination. Iopamidol does not dissociate in
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water and remains molecular in solution (Duirk et al., 2011; Tian et al., 2014).
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Therefore, the overall reaction can be expressed as follows:
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(1)
After integrating Eq. (1), the following expression was obtained:
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dC Cl 2 Cl 2 = k obs C = k app [ HOCl ]T C dt
ln
C0 Cl2 Cl2 = k obs t = k app [HOCl ]T t Ct
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Here,
Cl2 k obs is the pseudo-first order rate constant of iopamidol chlorination,
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which can be calculated from the slope of the fitted lines in Fig. 1. Furthermore, as the
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relationship of
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in Fig. 1 (R2 = 0.988), the relation between
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constant of iopamidol chlorination) and
Cl2 k obs to the total concentration of chlorine species ([HOC] T) is linear
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Cl2 k app (the apparent second-order rate
Cl2 k obs can be obtained from Eq. (2).
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3.1.2. Effect of pH on the reaction rate constants
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It is known that dissociation and distribution of chlorine species in water highly
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depend upon the solution pH (Acero et al., 2007). Besides, the degradation
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mechanisms and pathways of organic matter during chlorination might also be greatly
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influenced by pH (Deborde et al., 2004; Xu et al., 2011; Zhang et al., 2013; Gallard
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and von Gunten, 2002). Therefore, the reactions between chlorine (200 µM) and
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iopamidol (5 µM) under different pHs were investigated in this study, and the
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pH-profile of
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5 - 9 were also presented in Fig. 2 (Eq. (3)).
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Cl2 k app was given in Fig. 2. The molar fractions of HOCl and OCl- in pH
As can be seen from Fig. 2, the calculated
Cl2 k app values of iopamidol
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chlorination were significantly increased with increasing solution pH. It is also
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concluded that iopamidol was much less reactive than other organic compounds such
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as phenol (Gallard and von Gunten, 2002), bisphenol A (Gallard et al., 2004), diuron
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(Acero et al., 2007), ametryn (Xu et al., 2009), chlorotoluron (Xu et al., 2011) and
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dinoseb (Zhang et al., 2013), which may be due to the limited access of chlorine to the
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reactive sites on the aromatic ring of the triiodinated structure (a steric effect). The
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reactivity between iopamidol and chlorine was significantly promoted under alkaline
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ACCEPTED MANUSCRIPT Cl2 k app at acidic conditions were also observed,
pHs (Fig. 2). However, the minimal
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where the dominant chorine species was HOCl (Fig. 2). The rational mechanisms
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should involve reactions between iopamidol and HOCl/OCl-, which were listed in Eqs.
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(4) and (5).
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HOCl ⇔ OCl - + H +
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iopamidol + HOCl → products k 1
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iopamidol + OCl - → products k 2
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where Ka1 is the acid dissociation constant of HOCl, and k1 and k2 are the rate
254
constants of the reactions in Eqs. (4) and (5), respectively. Thus, the chlorination rate
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of iopamidol can be expressed in the following Eq. (6).
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Ka1 = 2.88×10-8 M
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(3) (4)
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d[iopamidol ] = k1[iopamidol ][ HOCl ] + k 2 [iopamidol ][OCl - ] (6) dt Assuming that the proportion of HOCl is α, where α = [HOCl]/HOCl] T, then
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[H + ] [OCl ] = (1 − α )[ HOCl ]T . Expression α = can be obtained from Eq. (3). K a1 + [H + ]
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Then the above three expressions can be substituted in then Eq. (6) can be rearranged
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as Eq. (7).
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d[iopamidol ] k1[H + ] + k 2 K a1 = [iopamidol ][ HOCl ]T dt K a1 + [H + ]
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The
Cl 2 k app =
(7)
Cl2 k app can be expressed as Eq. (8).
k 1 [H + ] + k 2 K a1 K a1 + [H + ]
(8)
The rate constants (k1 and k2) were determined by nonlinear least-squares Cl2 k app at different pHs using the
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regression analysis of the experimental data of
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function of nlinfit in Matlab 7.4.0 (R2007a). The calculated values of k1 and k2 were
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ACCEPTED MANUSCRIPT 1.66±0.09×10-3 M-1 s-1 and 0.45±0.02 M-1 s-1, respectively. k1 and k2 were slightly
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smaller than those obtained by Wendel et al. (2014) (1.5±2.5×10-3 M-1 s-1 and
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0.94±0.03 M-1 s-1), which might be attributed to the different pH range applied in each
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research. It is obvious that k2 was much greater than k1, which indicated that OCl- was
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more reactive toward iopamidol than HOCl. The pH effect in Fig. 2 could also be
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explained by the rate constants of the two elementary reactions. The
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electron-with-drawing effect caused by the carbonyl function groups on the aromatic
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ring, is prone to attract negatively charged ClO- rather than the neutral HOCl
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(Deborde and von Gunten, 2008). It is also confirmed that OCl- is a much more
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powerful chlorination agent than HOCl towards iopamidol (Thomm and Wayman,
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1969; Deborde and von Gunten, 2008). This result was consistent with previous
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studies regarding the chlorination kinetics of many inorganic and organic compounds
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(Thomm and Wayman, 1969; Deborde and von Gunten, 2008; Xu et al., 2009; 2011;
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Wendel et al., 2014).
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3.2. Chloramination of iopamidol
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3.2.1. Chloramination kinetics
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Some studies have confirmed that the chloramination of organic compounds
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followed second-order kinetics (Cimetiere et al., 2009; Xu et al., 2012). However, due
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to the weak oxidation capacity and self-dissociation of chloramines, the
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chloramination of organic compounds might involve complicated reactions. For
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instance, Wendel et al. reported that no significant degradation of iopamidol by
289
monochloramine was found within 24 h, regardless of the pH (Wendel et al., 2014).
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However, as shown in Fig. 3, a pseudo-second-order model can depict the
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experimental data well. Therefore, the overall reaction rate can be expressed as
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ACCEPTED MANUSCRIPT Eq. (10), which then can be integrated to get Eq. (11).
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−
dC NH 2Cl 2 = k obs C dt
(10)
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1 1 NH 2Cl − = k obs t Ct C 0
(11)
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NH 2Cl NH 2Cl k obs = k app [ NH 2 Cl ]T
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where C is the instant concentration of iopamidol, [NH2Cl] T is the total initial
297
concentration of chloramine and
298
iopamidol chloramination. As presented in Fig. 3, the slopes of the linearly fitted lines
299
(R2> 0.985) are the values of
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linear (R2> 0.998) so that Eq. (12) can be drawn, where
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third-order rate constant of iopamidol chloramination.
(12)
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NH 2Cl k app is the apparent
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3.2.2. Effect of pH on the reaction rate constants It is believed that NH2Cl is unstable in solution and can undergo a series of
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auto-decomposition reactions, resulting in the formation of complex combined
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chlorine species (Valentine and Jafvert, 1988). Therefore, the oxidation capacity of
307
chloramines is highly related to solution pH (Valentine and Jafvert, 1988; Bi et al.,
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2013). The influence of pH on iopamidol chloramination was then investigated in the
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range of 5 – 9, and the calculated
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NH 2Cl k app were plotted in Fig. 4.
As shown in Fig. 4, the trend of
NH 2Cl k app with pH values during iopamidol
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chloramination was neither monotone increasing nor decreasing. The distinct
312
maximum of
313
alkaline and acidic conditions. The phenomena could be explained by the coexistence
NH 2Cl k app appeared at pH 7, while much lower values were observed in
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solution. NHCl2 can form from the hydrolysis (Eqs. (13)-(15)) (Deinzer et al., 1978;
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Vikesland et al., 2001) and the acid catalyzed disproportionation of NH2Cl (Valentine
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and Jafvert, 1988). The proportional distributions of NH2Cl and NHCl2 were also
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shown in Fig. 4 (Nicholson et al., 1994; Vikesland et al., 2001).
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NH 2 Cl + H 2 O ⇔ HOCl + NH 3
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NH 2 Cl + HOCl ⇔ NHCl2 + H 2 O
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NH 2 Cl + NH 2 Cl ⇔ NHCl 2 + NH 3
(13)
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As can be seen in Fig. 4, there is no linear relationship between
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(15) NH 2Cl k app values
323
and the proportion of NH2Cl or NHCl2, which indicated their low reactivity toward
324
iopamidol. The negligible and lowest
325
the main combined chlorine species, NH2Cl, and iopamidol. However,
326
5 and 6 increased slightly, which can be concluded that the reactivity of NHCl2 with
327
iopamidol was also weak (Fig. 4). The hydrolysis was demonstrated to play a key role
328
in governing the overall decomposition rate of monochloramine in water in the
329
presence of natural organic matter (NOM) (Duirk et al., 2005; Duirk and Valentine,
330
2006). Moreover, the free chlorines in equilibrium with monochloramine were
331
demonstrated to contribute to the oxidation of As (III) (Dodd et al., 2006). Similarly,
332
the possible explanation compatible with all the available data in this study may be
333
that the free chlorines (i.e., HOCl and OCl-) were the predominant reactive oxidants
334
with iopamidol while the combined chlorine (i.e., NH2Cl and NHCl2) can not degrade
335
the compound effectively (Fig. 4).
NH 2Cl k app at pH 9 indicates no reaction between
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NH 2Cl k app at pH
336
As concluded above, OCl- was the more reactive chorine species with iopamidol
337
than HOCl (Eqs. (3), (13), (14) and (15)). The complicated balance among reactions 14
ACCEPTED MANUSCRIPT at different pHs exhibited the eventual results in this study. It can also be seen that
339
although the chlorination and chloramination of iopamidol followed different reaction
340
kinetics, the predominant reactants with iopamidol were identical (i.e., HOCl and
341
OCl-). The different generation routes of free chlorines derived from the hydrolysis of
342
chloramines, which highly depended on pH, made the overall reaction rate
343
significantly distinct from that during chlorination. Further investigation is still
344
needed to differentiate the role of chloramines and free chlorines in the decomposition
345
of iopamidol.
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346
3.3. Degradation pathways and DBP formation during chlor(am)ination of
348
iopamidol
349
3.3.1. Degradation pathways
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Previous studies on the degradation of ICM by simulated solar radiation
351
photolysis (Pérez et al., 2009), advanced oxidation/reduction processes (Jeong et al.,
352
2010), TiO2-photocatalyzed transformation (Sugihara et al., 2013), chlorination
353
(Wendel et al., 2014) as well as UV irradiation (Tian et al., 2014), have revealed that
354
deiodination is the major route. Besides, hydroxylated and chlorinated derivatives of
355
the target compounds might also be formed during chlorination and chloramination
356
(Losito et al., 2000; Zambonin et al., 2000; Xu et al., 2011; Xu et al., 2012; Bi et al.,
357
2013; Zhang et al., 2013). Wendel et al. (2014) identified the organic iodinated DBPs
358
with side chain cleavage as well as the exchange of iodine by chlorine during the
359
transformation of iopamidol by chlorine. On the basis of these results, the chlorination
360
and chloramination intermediates of iopamidol were analyzed and identified in this
361
work. Chromatographic retention time and mass spectral data for the proposed
362
structures were presented in Fig. 5 and Table S1. The molecular ion of iopamidol,
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350
15
ACCEPTED MANUSCRIPT 363
corresponding to the (m+H)/z peak, was 777. The products characterized with m/z 651 and 686.5 were correlated to the
365
substitution of iodine (126) by one hydrogen atom (1.0) or chloro atom (35.5),
366
respectively (Fig. 5 and Table S1). Moreover, the stepwise deiodination of iopamidol
367
was accompanied by the addition of hydroxyl groups and chloro atoms at the iodo
368
sites on the aromatic ring. Then the ions with m/z of 595, 503.5, 485, 467, 469, 434.5,
369
450.5, 561 and 576.5 were identified as different derivatives of the parent compound
370
with partial or complete iodo sites being substituted by hydroxyl groups and/or chloro
371
atoms (Fig. 5 and Table S1). The products inferred here were a bit different from
372
those reported by Wendel et al. (2014), which might be attributed to the completely
373
different reaction conditions of pH, reactant concentrations and oxidation time in each
374
research. However, the main deiodination and mechanisms of iopamidol chlorination
375
were internally coherent. The detected intermediates of iopamidol during
376
chloramination were basically the same as those during chlorination, but the
377
corresponding reaction time was much longer. In summary, the degradation pathways
378
of iopamidol during chlor(am)ination were proposed and exhibited in Fig. 5.
SC
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380
3.3.2. DBPs formation
381
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379
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364
As illustrated in Section 3.3.1, the deiodinated, hydroxylated and chlorinated
382
products of iopamidol during chlorination and chloramination might form and
383
facilitate the subsequent attack by oxidants in DBPs formation. Meanwhile, the
384
gradual deiodination of iopamidol would lead to the release of iodide in solution
385
(Steger-Hartmann et al., 2002; Doll and Frimmel, 2004; Jeong et al., 2010; Tian et al.,
386
2014), which can be further oxidized to HOI (Richardson et al., 2012) and lead to the
387
formation of iodinated DBPs. Therefore, the regular DBPs and iodinated DBPs
16
ACCEPTED MANUSCRIPT 388
formation during chlor(am)ination was measured, and the results were summarized in
389
Table 1. As exhibited in Table 1, regular DBPs (including chloroform (CF),
391
dichloroacetonitrile (DCAN), trichloroacetic acid (TCAA) and dichloroacetic acid
392
(DCAA)) and iodinated DBPs (including CHCl2I and CHClI2) were detected during
393
iopamidol chlorination. DCAN, DCAA and TCAA constituted the majority of regular
394
DBPs, which may be related to the comparatively stronger oxidation capacity of
395
chlorine upon the peptide groups of iopamidol (Hong et al., 2009). CHCl2I was the
396
main iodinated DBPs while no CHI3 was measured. The CHO cell chronic
397
cytotoxicity data also clearly indicated that chlorination of iopamidol generated a
398
toxic mixture of DBPs (Wendel et al., 2014). The DBPs especially iodinated DBPs
399
(CHCl2I and CHClI2) might be responsible for the enhanced toxicity of the
400
chlorinated iopamidol solution.
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390
The regular DBPs detected during iopamidol chloramination include trace
402
DCAN but no haloacetic acids due to the weaker oxidation capability of chloramines
403
than chlorine. The findings that chloramination produced significantly less regular
404
DBPs than chlorination agreed well with former studies (Guay et al., 2005; Bougeard
405
et al., 2010). However, the chloramination of iopamidol led to the formation of
406
slightly higher iodinated DBPs, remarkable CHI3, but much less CHCl2I and CHClI2
407
compared to those during chlorination. The organoleptic threshold concentration of
408
CHI3 is the lowest in all of the iodinated DBPs, which lies between 0.03 and 1.0 µg
409
L-1 (Cancho et al., 2001). Therefore, the risk of CHI3-related problems was highly
410
enhanced during chloramination of waters containing iopamidol.
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401
411
The formation of iodinated DBPs was due to the oxidation of iodide by chlorine
412
and chloramines (Bichsel and von Gunten, 1999; 2000). The enhanced formation of
17
ACCEPTED MANUSCRIPT 413
iodinated DBPs and induction of CHI3 during chloramination were in agreement with
414
other studies (Bichsel and von Gunten, 1999; 2000). It is also inferred from Table 1
415
that the iodine conversion from iopamidol to iodinated DBPs distinctly increased by
416
40% during chloramination compared to that during chlorination.
418
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417
3.4. Practical Implications
Iopamidol, the most frequently detected ICM, was also reported to be the most
420
important contributor to the formation of highly toxic iodinated DBPs among the
421
investigated ICM (Duirk et al., 2011). However, due to the structure stability and
422
nontoxicity, the features of iopamidol during chlor(am)ination are not fully
423
understood yet. However, it was evident from the pH effect in this study that the
424
degradation of iopamidol by chlor(am)ine might be highly favored in real waters at
425
circumneutral pHs (Figs. 2 and 4).
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419
The unified degradation pathways of iopamidol during chlori(am)nation
427
provided a deep insight on the transformation of this triiodinated compound to
428
iodinated DBPs. Highly toxic iodinated DBPs, especially CHI3, were formed during
429
chloramination, which greatly enhanced the toxicity of the disinfected waters.
430
Therefore, the disinfection risk of chloramines should be concerned for waters
431
polluted with iopamidol. Moreover, the results obtained here were from the
432
experiments conducted in purified water in the absence of NOM. Further research
433
regarding the effects of NOM on iopadimal chlor(am)ination as well as iodinated
434
DBPs formation should be explored so as to adopt feasible technology for the control
435
these highly toxic DBPs in drinking water treatment processes.
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436 437
4. Conclusions
18
ACCEPTED MANUSCRIPT 438
(1) The chlorination kinetics of iopamidol can be described by a second-order Cl2 k app
model, first-order in iopamidol and first-order in chlorine concentrations. The
440
significantly increased with solution pH. The reaction rate constants of iopamidol
441
with HOCl and OCl- were 1.66±0.09×10-3 M-1 s-1 and 0.45±0.02 M-1 s-1, respectively.
442
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439
(2) The chloramination of iopamidol fitted third-order kinetics, second-order in NH 2Cl k app reached a
iopamidol and first-order in chloramine concentrations. The
444
maximum at pH 7 but lowered evidently in both alkaline and acidic conditions. It was
445
thus inferred that the free chlorines can degrade iopamidol effectively while the
446
combined chlorines can not.
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443
(3) The main intermediates during chlor(am)ination of iopamidol were identified
448
using UPLC-ESI-MS. The degradation pathways were characterized, including
449
stepwise deiodination accompanied by the addition of hydroxyl groups and chloro
450
atoms at the iodo sites on the aromatic ring of iopamidol.
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447
451
(4) Regular DBPs (including CF, DCAN, TCAA and DCAA) and iodinated
452
DBPs (including CHCl2I and CHClI2) were measured during chlorination of
453
iopamidol.
454
chloramination. The iodine conversion to iodinated DBPs distinctly increased during
455
chloramination compared with that during chlorination.
457
formation
was
remarkable
during
iopamidol
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CHI3
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456
However,
Acknowledgments
458
This study was supported in part by the Natural Science Foundation of China
459
(No. 51678354 and 51478323), State Key Laboratory of Pollution Control and
460
Resource Reuse Foundation in China (No. PCRRK16005), the National Major
461
Science and Technology Project of China (No. 2015ZX07406004) and the Ministry of
462
Science and Technology in Taiwan (and 104-2221-E-327-001-MY3). 19
ACCEPTED MANUSCRIPT 463
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polychaete Platynereis dumerilii. Environ. Sci. Technol. 47, 10868-10876.
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Zhang, T.Y., Xu, B., Hu, C.Y., Li, M., Xia, S.J., Tian, F.X., Gao, N.Y., 2013.
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Degradation kinetics and chloropicrin formation during aqueous chlorination of
649
dinoseb. Chemosphere 93, 2662-2668.
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Table Table 1. Formation of regular and iodinated DBPs during chlorination and chloramination of iopamidol a Oxidation process
CF
22.23 ± 1.41 b
DCAN
221.27 ± 5.66
DCAA
55.85 ± 0.66
TCAA
302.63 ± 6.36
CHCl2I
154.62 ± 4.36
CHClI2
35.14 ± 3.76
12.02 ± 2.42
CHI3
ND
168.47 ± 13.45
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Iodinated DBPs
Chloramination
iodine conversion to iodinated DBPs (%) d Notes:
ND c
5.55 ± 1.43 ND
ND
6.24 ± 1.86
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Regular DBPs
Chlorination
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Detected DBPs (µg -1 L)
3.22 ± 0.04
4.64 ± 0.25
Contact time 7 d for chlorination or chloramination of iopamidol.
b
The standard deviation was obtained from triplicate measurements.
c
ND = Not-detected.
d
Iodine conversion from iopamidol to iodinated DBPs was calculated as the total
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iodine molar quantity of iodinated DBPs divided by the initial concentration of
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ACCEPTED MANUSCRIPT List of Figure Captions Fig. 1. Pseudo-first-order kinetics plot of iopamidol chlorination and the relationship of
Cl2 k obs to [HOCl ]T at 25 ±1oC, pH 7, [iopamidol]0 = 5 µM, [phosphate buffer] =
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10 mM and five different chlorine dosages. Cl
Fig. 2. Effect of pH on the apparent second-order rate constant ( k app2 ) of iopamidol chlorination. ([buffer] = 10 mM, [iopamidol]0 = 5 µ M, [Cl2]0 = 200 µM)
NH 2Cl k obs to [ NH 2 Cl ]T at 25 ±1oC, pH 7, [iopamidol]0 = 5 µM,
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relationship of
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Fig. 3. Pseudo-second-order kinetics plot of iopamidol chloramination and the
[phosphate buffer] = 10 mM and four different chloramine dosages. NH Cl
Fig. 4. Effect of pH on the apparent third-order rate constant ( k app 2 ) of iopamidol chloramination. ([buffer] = 10 mM, [iopamidol]0 = 5 µ M, [NH2Cl]0 = 250 µM)
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chloramination.
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Fig. 5. Proposed degradation pathways of iopamidol during chlorination or
ACCEPTED MANUSCRIPT 6.94 x10-5 5.56
obs
kCl2 (s-1)
5
4.2 2.78
4
0 0
3
200
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ln(C 0/C t)
1.39
400 600 [Cl ] (µM) 2 0
800
1000
2
[Cl2]0=50µ M, R =0.996 2
[Cl2]0=100µ M, R =0.998
2
2
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[Cl2]0=200µ M, R =0.997 2
[Cl2]0=500µ M, R =0.994
1
2
0
0
8
16
24
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40 48 56 Time (h)
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ACCEPTED MANUSCRIPT 1
0.5 HClO 0.42
-1
-1
kapp (M s )
0.33 0.6
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Cl2
Molar fraction
0.8
0.4
0.17
0.2
5
6
7 pH
8
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0.083
-
ClO
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ACCEPTED MANUSCRIPT 4.17 x10-3 2.78
obs
kNH2Cl (M -2 s-1)
2
1.5
0
1
0
200
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-1
1/Ct-1/C0 (M )
1.39
400 600 NH Cl (µM) 2
800
2
[NH 2Cl]0=50µ M, R =0.997 2
[NH 2Cl]0=100µ M, R =0.994
0.5
2
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[NH 2Cl]0=250µ M, R =0.985 2
[NH 2Cl]0=1000µ M, R =0.994
0
48
96
144 192 Time (h)
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ACCEPTED MANUSCRIPT 1
8.33 NH2Cl
6.94
-2 NH2Cl
kapp
4.17
0.4
NHCl2
2.78
0.2
5
6
7 pH
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1.39
8
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-1
5.56 0.6
(M s )
0.8
-3
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Proportional distribution
X10
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0
ACCEPTED MANUSCRIPT HO O I O CH 3 NH OH
OH NH I NH I
OH
HO O
deiodination CH3
OH
NH I
OI
NH OH
NH
O
OH Iopamidol(M=777)
O 651
OH
OH
addition of Cl HO O I CH3 O
OH NH I NH Cl O
OH
CH 3 OH
NH Cl O
OH
OH
595
CH 3 NH Cl O 561
OH
Cl O 576.5
OH
NH
O
CH 3 O
NH
OH
NH
Cl O 434.5
OH
OH NH OH NH
HO O
OH
HO O
OH
substitution of I by OH
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deiodination
CH3
OH
NH
OH
NH OH
OI
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CH 3
NH
OI
OH NH OH NH
HO O
OH
HO O
NH Cl NH
OI
substitution of I by OH
deiodination
OH
HO O
OH
Cl 686.5
substitution of I by Cl
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OH
NH
OH
OH
NH
OH
Cl O 450.5
OH
addition of Cl
substitution of I by Cl
OH
NH
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HO O Cl O CH3 NH
OH
NH
Cl O 469
addition of OH OH OH
addition of OH
OH NH Cl NH
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HO O Cl CH 3 O
OH
NH
Cl O
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OH
HO O Cl CH3 O
503.5
OH
OH NH OH NH OH
NH OH
HO O OH CH 3 O
Cl O 485
OH
Further degradation products
Fig. 5
OH NH OH NH OH
NH OH
Cl O 467
OH
ACCEPTED MANUSCRIPT Highlights The chlorination kinetics of iopamidol can be described by a second-order model. Iopamidol chlorination significantly increased with solution pH. NH 2Cl k obs
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Iopamidol chloramination fitted third-order model and maximum occurred at pH 7.
The destruction pathways of iopamidol by chlor(am)ination were proposed.
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More iodinated DBPs especially CHI3 was formed in chloramination than
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chlorination.
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DOI:
10.1016/j.chemosphere.2017.06.012
Reference:
CHEM 19405
To appear in:
ECSN
Received Date: 23 February 2017 Revised Date:
22 May 2017
Accepted Date: 4 June 2017
Please cite this article as: Tian, F.-X., Xu, B., Lin, Y.-L., Hu, C.-Y., Zhang, T.-Y., Xia, S.-J., Chu, W.-H., Gao, N.-Y., Chlor(am)ination of iopamidol: Kinetics, pathways and disinfection by-products formation, Chemosphere (2017), doi: 10.1016/j.chemosphere.2017.06.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Chlor(am)ination of iopamidol: Kinetics, pathways
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and disinfection by-products formation
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Fu-Xiang Tian1, Bin Xu1*, Yi-Li Lin2, Chen-Yan Hu3, Tian-Yang Zhang1, Sheng-Ji
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Xia1, Wen-Hai Chu1, Nai-Yun Gao1
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1. State Key Laboratory of Pollution Control and Resource Reuse, Institute of
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Disinfection By-product Control in Water Treatment, College of Environmental
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Science and Engineering, Tongji University, Shanghai 200092; P. R. China
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2. Department of Safety, Health and Environmental Engineering, National Kaohsiung
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First University of Science and Technology, Kaohsiung 824, Taiwan, R.O.C.
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3. College of Environmental and Chemical Engineering, Shanghai University of
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Electric Power, Shanghai 200090; P. R. China
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*Corresponding author: Bin Xu
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Email: [email protected]
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Phone: +86-13918493316
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1
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Abstract The degradation kinetics, pathways and disinfection by-products (DBPs)
26
formation of iopamidol by chlorine and chloramines were investigated in this paper.
27
The chlorination kinetics can be well described by a second-order model. The
28
apparent second-order rate constants of iopamidol chlorination significantly increased
29
with solution pH. The rate constants of iopamidol with HOCl and OCl- were
30
calculated as 1.66±0.094×10-3 M-1 s-1 and 0.446±0.022 M-1 s-1, respectively. However,
31
the chloramination of iopamidol fitted well with third-order kinetics and the
32
maximum of the apparent rate constant occurred at pH 7. It was inferred that the free
33
chlorine (i.e., HOCl and OCl-) can react with iopamidol while the combined chlorine
34
species (i.e., NH2Cl and NHCl2) were not reactive with iopamidol. The main
35
intermediates during chlorination or chloramination of iopamidol were identified
36
using ultra performance liquid chromatography - electrospray ionization-mass
37
spectrometry (UPLC-ESI-MS), and the destruction pathways including stepwise
38
deiodination, hydroxylation as well as chlorination were then proposed. The regular
39
and iodinated DBPs formed during chlorination and chloramination of iopamidol
40
were measured. It was found that iodine conversion from iopamidol to toxic iodinated
41
DBPs distinctly increased during chloramination. The results also indicated that
42
although chloramines were much less reactive than chlorine toward iopamidol, they
43
led to the formation of much more toxic iodinated DBPs, especially CHI3.
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Keywords:
iopamidol;
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by-products (DBPs).
kinetics;
chlorination;
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2
chloramination;
disinfection
ACCEPTED MANUSCRIPT 49
1. Introduction Iodinated X-ray contrast media (ICM) have been widely used for imaging of
51
organs or blood vessels during diagnostic tests (Perez et al., 2006; Duirk et al., 2011).
52
Generally, they are administered at high daily doses in human medicine and then be
53
excreted without much metabolization (Schulz et al., 2008). Therefore, ICM have
54
been frequently detected in wastewater and surface waters at elevated concentrations
55
(sometimes more than 10 µg L-1) (Perez et al., 2006; Schulz et al., 2008; Sugihara et
56
al., 2013). As one type of emerging waterborne pollutants, ICM have drawn more and
57
more concerns recently due to their extremely stable structure and evidenced
58
conversion to highly toxic iodinated disinfection by-products (DBPs) (Perez et al.,
59
2006; Jeong et al., 2010; Duirk et al., 2011; Sugihara et al., 2013; Tian et al., 2014).
60
Iopamidol is the most frequently detected ICM in waters at concentrations of several
61
µg L-1 (Ternes and Hirsch, 2000; Perez et al., 2006; Duirk et al., 2011). Chlorinated
62
and chloraminated source waters containing iopamidol were reported to be genotoxic
63
and cytotoxic to mammalian cells (Plewa et al., 2004; Richardson et al., 2008). Duirk
64
et al. have demonstrated that ICM, especially iopamidol, act as an important organic
65
iodine source in the formation of iodinated DBPs (Duirk et al., 2011), which are much
66
more toxic than the regular DBPs such as trihalomethanes (THMs) and haloacetic
67
acids (Bichsel and von Gunten, 2000; Smith et al., 2010; Richardson et al., 2012).
68
Moreover, the degradation of iopamidol could lead to the formation of intermediates
69
that are partially or completely iodinated, chlorinated or hydroxylated on the aromatic
70
ring (Tian et al., 2014; Wendel et al., 2014). The iodinated aromatic DBPs have also
71
been reported to present significantly higher developmental toxicity and growth
72
inhibition than aliphatic iodinated DBPs and regulated DBPs (Yang and Zhang, 2013;
73
Pan et al., 2016).
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3
ACCEPTED MANUSCRIPT Chlorine is the most common oxidant and disinfectant used in water treatment
75
plants nowadays (Bull et al., 1995). Therefore, extensive studies have investigated the
76
chlorination of organic compounds such as endocrine disruptors (Deborde et al., 2004;
77
Gallard et al., 2004), antibacterials (Dodd and Huang, 2007), herbicides (Duirk and
78
Collette, 2006; Acero et al., 2007; Xu et al., 2011; Zhang et al., 2013) and
79
pharmaceuticals (Acero et al., 2010). However, the formation of undesirable DBPs
80
during chlorination has received high concerns because of their high toxicity and
81
carcinogenicity (Hu et al., 2002; Richardson et al., 2012). Chloramines are therefore
82
adopted as a secondary disinfectant to reduce DBP formation in drinking water
83
because chloramines are weaker disinfectants and can produce much less DBPs
84
compared to chlorine (Hua and Reckhow, 2007). Chloramination of many organic
85
compounds have been reported, such as organophosphorus pesticides (Duirk et al.,
86
2010), nitrogenous organic compounds (Yang et al., 2010), algal organic matter (Fang
87
et al., 2010), herbicide (Xu et al., 2012), and oxytetracycline (Bi et al., 2013).,.
88
However, the formation of iodinated DBPs has also been reported during
89
chloramination at levels higher than those during chlorination. Both chlorine and
90
chloramines can oxidize iodide to hypoiodois acid (HOI). However, the subsequent
91
reactions to form iodate are much faster than reactions those to form iodinated DBPs
92
during chlorination, while the corresponding reactions to form iodite and iodate are
93
much slower than those to form iodinated DBPs during chloramination (Bichsel and
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von Gunten, 1999; 2000. Richardson et al., 2012).
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Due to their structure stability, the degradation kinetics and pathways of ICM
96
during chlorination and chloramination have not been fully explored. As the most
97
reported organic iodine contributors to iodinated DBPs (Duirk et al., 2011; Tian et al.,
98
2014; Wang et al., 2014; Ye et al., 2014) and persistent organic pollutants (Doll and
4
ACCEPTED MANUSCRIPT Frimmel, 2004; Huber et al., 2005; Schulz et al., 2008; Jeong et al., 2010; Sugihara et
100
al., 2013), ICM, especially iopamidol, are beginning to gain more and more attention
101
in water treatment processes. However, limited studies have focused on the
102
degradation of iopamidol during common oxidation process (Tian et al., 2014; Wang
103
et al., 2014; Wendel et al., 2014). Wendel et al. (2014) investigated the reaction
104
kinetics, iodine fate, reaction pathways as well as mammalian cell toxicology of
105
iopamidol during chlorination, but the chloramination kinetics and DBPs, especially
106
iodinated DBPs formation were not involved. Therefore, it is of great practical
107
significance to investigate and understand the mechanisms and DBPs formation of
108
iopamidol during chlorination and chloramination.
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The objectives of this study were (1) to investigate the degradation kinetics and
110
the effect of pH during chlorination and chloramination of iopamidol and (2) to
111
elucidate the degradation pathways and the formation of regular and iodinated DBPs
112
during chlorination and chloramination of iopamidol. This study aimed to shed light
113
on the possible transformation mechanisms of ICM to toxic iodinated DBPs by
114
oxidants in water treatment.
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2. Materials and methods
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2.1. Chemicals
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All chemicals were at least of analytical grade and used without further
119
purification. The calibration standards, internal standards, surrogate standards for
120
volatile DBPs (including THMs with 3 hydrogen atoms being replaced by chlorine
121
and/or bromine (THM4), vinyl chloride (VC), haloketones (HKs), haloacetonitriles
122
(HANs) and chloropicrin (CP)), EPA 552.2 haloacetic acids mix, CHI3 (99%),
123
iodoacetic acid (≥ 99.0%) standards, sodium hypochlorite (NaOCl) solution (available
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ACCEPTED MANUSCRIPT chlorine 4.00-4.99%), ammonium acetate (≥98%), NaOH (≥98%), KH2PO4 (≥99.0%),
125
Na2CO3 (≥99.0%), and NaHCO3 (≥99.0%) were purchased from Sigma-Aldrich (St.
126
Louis, MO, USA). The CHClI2 and CHCl2I standards were obtained from CanSyn
127
Chemical Corp. (Canada). Iopamidol (99.6%) was obtained from U.S.Pharmacopeia.
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Formic acid solution (49-51%) was purchased from Fluka (St. Louis, MO, USA).
129
Triiodoacetic acid (90%) standard solution was obtained from Toronto Research
130
Chemicals Inc. (Canada). Methyl tert-butyl ether (MtBE) and acetonitrile were
131
obtained from J.T. Baker (USA). Analytical grade reagents including Na2S2O3,
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Na2SO4 and H2SO4 were purchased from Sinopharm Chemical Reagent Co., Ltd.
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(Shanghai, China). All solutions were prepared with ultra-pure water produced by a
134
Milli-Q water purification system (Millipore, USA).
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The monochloramine (NH2Cl) solution was freshly prepared by mixing NH4Cl
136
and NaOCl solutions at a Cl2/N molar ratio of 0.8 at pH 8.5 (Mitch and Sedlak, 2002).
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2.2. Experimental procedures
Chlorination and chloramination of iopamidol were carried out in a batch reactor
140
fixed in a thermostatic culture oscillator at controlled temperature of 25±1 oC. The
141
batch reactor was a 250 mL bottle equipped with a dispenser. Experiments were
142
conducted in duplicate under pseudo-first-order conditions, while the dosage of
143
oxidant was at least 10 times higher than that of iopamidol. In kinetic experiments, the
144
Cl2 concentrations were controlled at 50, 100, 200, 500 and 1000 µM while the
145
NH2Cl concentrations were 50, 100, 25 and 1000 µM, respectively. Experiments were
146
initiated by adding Cl2 or NH2Cl stock solution to the reactor containing iopamidol
147
with concentration of 5 µM. The solution was buffered at pH 5 - 9 using 10 mM
148
phosphate (for pH 5-8) or carbonate (for pH 9) buffer, and the pH was adjusted with
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ACCEPTED MANUSCRIPT small volume of 0.01, 0.1 or 1 M H2SO4 and/or NaOH. At different reaction time,
150
1 mL of solution was rapidly transferred into an ultra performance liquid
151
chromatography (UPLC) vial containing Na2SO3 solution (20 mM) at 1.2 times of
152
oxidant concentration to quench the reaction, and then the samples were analyzed
153
using UPLC or ultra performance liquid chromatography-electrospray ionization-mass
154
spectrometry (UPLC-ESI-MS) as soon as possible.
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The experiments of DBPs formation were conducted in triplicate under
156
headspace-free conditions in 40-mL glass screw-cap amber vials with PTFE-lined
157
septa in dark at 25 ±1 o) in a thermostatic biochemical incubator. The concentrations
158
of iopamidol and chlor(am)ine were 10 and 100 µM, respectively. At the scheduled
159
time of 7 d, the reaction was quenched using NH4Cl (for regular DBPs) or Na2SO3
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(for iodinated DBPs) at 1.2 times of the oxidant concentration, and the samples were
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then extracted for analysis as soon as possible (Lin et al., 2014).
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The experiments for the identifying of intermediates during iopamidol
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chlor(am)ination were conducted at initial iopamidol concentration of 25 µM for
164
higher analytical resolution. The solutions were buffered using 10 mM phosphate and
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the pH was adjusted with H2SO4 and/or NaOH. After dosed with 250 µM
166
chlor(am)ine, the samples were collected and quenched with Na2SO3 solution at the
167
scheduled time of 0, 2, 4, 8, 12 and 24 h for chlorination, and 0, 24, 48, 96, 120, 144
168
and 168 h for chloramination, respectively. Finally, with no further extraction steps,
169
the samples were directly analyzed using UPLC-ESI-MS immediately.
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2.3. Analytical methods
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Iopamidol was analyzed using UPLC (Waters, USA) equipped with a XTerra®
173
MS C18 column (4.6 mm×250 mm i.d., 5 µm film thickness, Waters, USA) and an
7
ACCEPTED MANUSCRIPT 174
UV detector at the wavelength 242 nm. The mobile phase was consisted of 10%/90%
175
(v/v) acetonitrile and Milli-Q water at a flow rate of 0.80 mL min-1. The injection
176
volume was 10 µL and the detection limit of iopamidol was 6.4×10-3 µM (5 µg L-1). The pH measurements were carried out with a regularly calibrated pH meter
178
(FE20-FiveEasy, Mettler Toledo, Switzerland) using standard buffer solutions
179
(Mettler Toledo, pH = 4.01, 7.00 and 9.21). The concentrations of Cl2 and NH2Cl
180
were measured using the N, N-diethyl-p-phenylenediamine (DPD) colorimetric
181
method (APHA, 1998).
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Methods for quantifying regular and iodinated DBPs were developed by
183
modifying the USEPA Method 551.1 (Munch and Hautman, 1995) and 552.2
184
(Hodgeson et al., 1995). Samples were extracted with MtBE, and the extracts were
185
analyzed using a gas chromatograph (GC-2010, Shimadzu, Japan) equipped with an
186
electron capture detector (ECD) and a HP-5 capillary column (30 m×0.25 mm i.d.,
187
0.25 µm film thickness, J&W, USA). The injector and detector temperatures were 200
188
and 290 οC, respectively, and the flow rate of the nitrogen carrier gas was 30 mL min-1
189
with pressure of 69.8 kPa. The temperature program for the analysis of regular DBPs
190
was as follows: hold at 37 οC for 10 min, ramp to 50 οC at rate of 5 οC min-1 and hold
191
for 5 min, and finally ramp to 260 οC at rate of 15 οC min-1 and hold for 10 min. The
192
temperature program for the analysis of iodinated DBPs was as follows: hold at 40 οC
193
for 10 min and then ramp to 260 οC at rate of 15 οC min-1 and hold for 10 min.
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The analysis of intermediates during iopamidol chlor(am)nation was carried out
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using a UPLC-ESI-MS system consisted of an Accela U-HPLC system, a TSQ
196
Quantum mass spectrometer (ESI source, Thermo Scientific Inc., USA) and an
197
XTerra® MS C18 column (250 mm×2.1 mm, i.d., 5 µm film thickness, Waters, USA).
198
Acetonitrile and 1% formic acid solution (10%/90%, v/v) were used as the mobile
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200
were as follows: spray voltage 4.0 kV, capillary temperature 350 oC, sheath gas
201
pressure 50 (arbitrary units), and auxiliary gas pressure 45 (arbitrary units). The MS
202
chromatograms were obtained both in total ion current (TIC) mode using full scans
203
(m/z 200-900) for mass spectra acquisition and the selected ion monitoring (SIM)
204
mode.
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3. Results and discussion
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3.1. Chlorination of iopamidol
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3.1.1. Chlorination kinetics
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The kinetics for the chlorination of organic compounds such as phenols,
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bisphenol A, chlortoluron, have been developed to be a second-order model,
211
first-order in chlorine and first-order in compound concentrations (Gallard and von
212
Gunten, 2002; Gallard et al., 2004; Xu et al., 2011). Based on this conclusion, the
213
relationship of ln (C0/Ct) to the reaction time (t) with different initial chlorine dosages
214
was analogously fitted and shown in Fig. 1, where C0 and Ct are the concentrations of
215
iopamidol (M)at reaction time of t = 0 and t = t, respectively.
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The good linear fit (R2>0.994) of experimental data was indicative of the
217
pseudo-first order kinetic for iopamidol chlorination. Iopamidol does not dissociate in
218
water and remains molecular in solution (Duirk et al., 2011; Tian et al., 2014).
219
Therefore, the overall reaction can be expressed as follows:
220
−
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(1)
After integrating Eq. (1), the following expression was obtained:
221
222
dC Cl 2 Cl 2 = k obs C = k app [ HOCl ]T C dt
ln
C0 Cl2 Cl2 = k obs t = k app [HOCl ]T t Ct
(2) 9
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Here,
Cl2 k obs is the pseudo-first order rate constant of iopamidol chlorination,
224
which can be calculated from the slope of the fitted lines in Fig. 1. Furthermore, as the
225
relationship of
226
in Fig. 1 (R2 = 0.988), the relation between
227
constant of iopamidol chlorination) and
Cl2 k obs to the total concentration of chlorine species ([HOC] T) is linear
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Cl2 k app (the apparent second-order rate
Cl2 k obs can be obtained from Eq. (2).
229
3.1.2. Effect of pH on the reaction rate constants
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It is known that dissociation and distribution of chlorine species in water highly
231
depend upon the solution pH (Acero et al., 2007). Besides, the degradation
232
mechanisms and pathways of organic matter during chlorination might also be greatly
233
influenced by pH (Deborde et al., 2004; Xu et al., 2011; Zhang et al., 2013; Gallard
234
and von Gunten, 2002). Therefore, the reactions between chlorine (200 µM) and
235
iopamidol (5 µM) under different pHs were investigated in this study, and the
236
pH-profile of
237
5 - 9 were also presented in Fig. 2 (Eq. (3)).
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Cl2 k app was given in Fig. 2. The molar fractions of HOCl and OCl- in pH
As can be seen from Fig. 2, the calculated
Cl2 k app values of iopamidol
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chlorination were significantly increased with increasing solution pH. It is also
240
concluded that iopamidol was much less reactive than other organic compounds such
241
as phenol (Gallard and von Gunten, 2002), bisphenol A (Gallard et al., 2004), diuron
242
(Acero et al., 2007), ametryn (Xu et al., 2009), chlorotoluron (Xu et al., 2011) and
243
dinoseb (Zhang et al., 2013), which may be due to the limited access of chlorine to the
244
reactive sites on the aromatic ring of the triiodinated structure (a steric effect). The
245
reactivity between iopamidol and chlorine was significantly promoted under alkaline
10
ACCEPTED MANUSCRIPT Cl2 k app at acidic conditions were also observed,
pHs (Fig. 2). However, the minimal
247
where the dominant chorine species was HOCl (Fig. 2). The rational mechanisms
248
should involve reactions between iopamidol and HOCl/OCl-, which were listed in Eqs.
249
(4) and (5).
250
HOCl ⇔ OCl - + H +
251
iopamidol + HOCl → products k 1
252
iopamidol + OCl - → products k 2
253
where Ka1 is the acid dissociation constant of HOCl, and k1 and k2 are the rate
254
constants of the reactions in Eqs. (4) and (5), respectively. Thus, the chlorination rate
255
of iopamidol can be expressed in the following Eq. (6).
256
−
Ka1 = 2.88×10-8 M
RI PT
246
(3) (4)
257
M AN U
SC
(5)
d[iopamidol ] = k1[iopamidol ][ HOCl ] + k 2 [iopamidol ][OCl - ] (6) dt Assuming that the proportion of HOCl is α, where α = [HOCl]/HOCl] T, then
258
[H + ] [OCl ] = (1 − α )[ HOCl ]T . Expression α = can be obtained from Eq. (3). K a1 + [H + ]
259
Then the above three expressions can be substituted in then Eq. (6) can be rearranged
260
as Eq. (7).
261
−
263 264
TE D
EP
d[iopamidol ] k1[H + ] + k 2 K a1 = [iopamidol ][ HOCl ]T dt K a1 + [H + ]
AC C
262
-
The
Cl 2 k app =
(7)
Cl2 k app can be expressed as Eq. (8).
k 1 [H + ] + k 2 K a1 K a1 + [H + ]
(8)
The rate constants (k1 and k2) were determined by nonlinear least-squares Cl2 k app at different pHs using the
265
regression analysis of the experimental data of
266
function of nlinfit in Matlab 7.4.0 (R2007a). The calculated values of k1 and k2 were
11
ACCEPTED MANUSCRIPT 1.66±0.09×10-3 M-1 s-1 and 0.45±0.02 M-1 s-1, respectively. k1 and k2 were slightly
268
smaller than those obtained by Wendel et al. (2014) (1.5±2.5×10-3 M-1 s-1 and
269
0.94±0.03 M-1 s-1), which might be attributed to the different pH range applied in each
270
research. It is obvious that k2 was much greater than k1, which indicated that OCl- was
271
more reactive toward iopamidol than HOCl. The pH effect in Fig. 2 could also be
272
explained by the rate constants of the two elementary reactions. The
273
electron-with-drawing effect caused by the carbonyl function groups on the aromatic
274
ring, is prone to attract negatively charged ClO- rather than the neutral HOCl
275
(Deborde and von Gunten, 2008). It is also confirmed that OCl- is a much more
276
powerful chlorination agent than HOCl towards iopamidol (Thomm and Wayman,
277
1969; Deborde and von Gunten, 2008). This result was consistent with previous
278
studies regarding the chlorination kinetics of many inorganic and organic compounds
279
(Thomm and Wayman, 1969; Deborde and von Gunten, 2008; Xu et al., 2009; 2011;
280
Wendel et al., 2014).
SC
M AN U
TE D
281
RI PT
267
3.2. Chloramination of iopamidol
283
3.2.1. Chloramination kinetics
EP
282
Some studies have confirmed that the chloramination of organic compounds
285
followed second-order kinetics (Cimetiere et al., 2009; Xu et al., 2012). However, due
286
to the weak oxidation capacity and self-dissociation of chloramines, the
287
chloramination of organic compounds might involve complicated reactions. For
288
instance, Wendel et al. reported that no significant degradation of iopamidol by
289
monochloramine was found within 24 h, regardless of the pH (Wendel et al., 2014).
290
However, as shown in Fig. 3, a pseudo-second-order model can depict the
291
experimental data well. Therefore, the overall reaction rate can be expressed as
AC C
284
12
ACCEPTED MANUSCRIPT Eq. (10), which then can be integrated to get Eq. (11).
293
−
dC NH 2Cl 2 = k obs C dt
(10)
294
1 1 NH 2Cl − = k obs t Ct C 0
(11)
295
NH 2Cl NH 2Cl k obs = k app [ NH 2 Cl ]T
296
where C is the instant concentration of iopamidol, [NH2Cl] T is the total initial
297
concentration of chloramine and
298
iopamidol chloramination. As presented in Fig. 3, the slopes of the linearly fitted lines
299
(R2> 0.985) are the values of
300
linear (R2> 0.998) so that Eq. (12) can be drawn, where
301
third-order rate constant of iopamidol chloramination.
(12)
SC
NH 2Cl k obs is the pseudo-second order rate constant of
NH 2Cl k app is the apparent
TE D
M AN U
NH 2Cl NH Cl k obs . The plot of k obs 2 toward [NH2Cl] T is also
302 303
RI PT
292
3.2.2. Effect of pH on the reaction rate constants It is believed that NH2Cl is unstable in solution and can undergo a series of
305
auto-decomposition reactions, resulting in the formation of complex combined
306
chlorine species (Valentine and Jafvert, 1988). Therefore, the oxidation capacity of
307
chloramines is highly related to solution pH (Valentine and Jafvert, 1988; Bi et al.,
308
2013). The influence of pH on iopamidol chloramination was then investigated in the
309
range of 5 – 9, and the calculated
310
AC C
EP
304
NH 2Cl k app were plotted in Fig. 4.
As shown in Fig. 4, the trend of
NH 2Cl k app with pH values during iopamidol
311
chloramination was neither monotone increasing nor decreasing. The distinct
312
maximum of
313
alkaline and acidic conditions. The phenomena could be explained by the coexistence
NH 2Cl k app appeared at pH 7, while much lower values were observed in
13
ACCEPTED MANUSCRIPT of complicated chlorine-based oxidative species as NH2Cl, NHCl2, HOCl and OCl- in
315
solution. NHCl2 can form from the hydrolysis (Eqs. (13)-(15)) (Deinzer et al., 1978;
316
Vikesland et al., 2001) and the acid catalyzed disproportionation of NH2Cl (Valentine
317
and Jafvert, 1988). The proportional distributions of NH2Cl and NHCl2 were also
318
shown in Fig. 4 (Nicholson et al., 1994; Vikesland et al., 2001).
319
NH 2 Cl + H 2 O ⇔ HOCl + NH 3
320
NH 2 Cl + HOCl ⇔ NHCl2 + H 2 O
321
NH 2 Cl + NH 2 Cl ⇔ NHCl 2 + NH 3
(13)
SC
(14)
As can be seen in Fig. 4, there is no linear relationship between
M AN U
322
RI PT
314
(15) NH 2Cl k app values
323
and the proportion of NH2Cl or NHCl2, which indicated their low reactivity toward
324
iopamidol. The negligible and lowest
325
the main combined chlorine species, NH2Cl, and iopamidol. However,
326
5 and 6 increased slightly, which can be concluded that the reactivity of NHCl2 with
327
iopamidol was also weak (Fig. 4). The hydrolysis was demonstrated to play a key role
328
in governing the overall decomposition rate of monochloramine in water in the
329
presence of natural organic matter (NOM) (Duirk et al., 2005; Duirk and Valentine,
330
2006). Moreover, the free chlorines in equilibrium with monochloramine were
331
demonstrated to contribute to the oxidation of As (III) (Dodd et al., 2006). Similarly,
332
the possible explanation compatible with all the available data in this study may be
333
that the free chlorines (i.e., HOCl and OCl-) were the predominant reactive oxidants
334
with iopamidol while the combined chlorine (i.e., NH2Cl and NHCl2) can not degrade
335
the compound effectively (Fig. 4).
NH 2Cl k app at pH 9 indicates no reaction between
AC C
EP
TE D
NH 2Cl k app at pH
336
As concluded above, OCl- was the more reactive chorine species with iopamidol
337
than HOCl (Eqs. (3), (13), (14) and (15)). The complicated balance among reactions 14
ACCEPTED MANUSCRIPT at different pHs exhibited the eventual results in this study. It can also be seen that
339
although the chlorination and chloramination of iopamidol followed different reaction
340
kinetics, the predominant reactants with iopamidol were identical (i.e., HOCl and
341
OCl-). The different generation routes of free chlorines derived from the hydrolysis of
342
chloramines, which highly depended on pH, made the overall reaction rate
343
significantly distinct from that during chlorination. Further investigation is still
344
needed to differentiate the role of chloramines and free chlorines in the decomposition
345
of iopamidol.
SC
RI PT
338
346
3.3. Degradation pathways and DBP formation during chlor(am)ination of
348
iopamidol
349
3.3.1. Degradation pathways
M AN U
347
Previous studies on the degradation of ICM by simulated solar radiation
351
photolysis (Pérez et al., 2009), advanced oxidation/reduction processes (Jeong et al.,
352
2010), TiO2-photocatalyzed transformation (Sugihara et al., 2013), chlorination
353
(Wendel et al., 2014) as well as UV irradiation (Tian et al., 2014), have revealed that
354
deiodination is the major route. Besides, hydroxylated and chlorinated derivatives of
355
the target compounds might also be formed during chlorination and chloramination
356
(Losito et al., 2000; Zambonin et al., 2000; Xu et al., 2011; Xu et al., 2012; Bi et al.,
357
2013; Zhang et al., 2013). Wendel et al. (2014) identified the organic iodinated DBPs
358
with side chain cleavage as well as the exchange of iodine by chlorine during the
359
transformation of iopamidol by chlorine. On the basis of these results, the chlorination
360
and chloramination intermediates of iopamidol were analyzed and identified in this
361
work. Chromatographic retention time and mass spectral data for the proposed
362
structures were presented in Fig. 5 and Table S1. The molecular ion of iopamidol,
AC C
EP
TE D
350
15
ACCEPTED MANUSCRIPT 363
corresponding to the (m+H)/z peak, was 777. The products characterized with m/z 651 and 686.5 were correlated to the
365
substitution of iodine (126) by one hydrogen atom (1.0) or chloro atom (35.5),
366
respectively (Fig. 5 and Table S1). Moreover, the stepwise deiodination of iopamidol
367
was accompanied by the addition of hydroxyl groups and chloro atoms at the iodo
368
sites on the aromatic ring. Then the ions with m/z of 595, 503.5, 485, 467, 469, 434.5,
369
450.5, 561 and 576.5 were identified as different derivatives of the parent compound
370
with partial or complete iodo sites being substituted by hydroxyl groups and/or chloro
371
atoms (Fig. 5 and Table S1). The products inferred here were a bit different from
372
those reported by Wendel et al. (2014), which might be attributed to the completely
373
different reaction conditions of pH, reactant concentrations and oxidation time in each
374
research. However, the main deiodination and mechanisms of iopamidol chlorination
375
were internally coherent. The detected intermediates of iopamidol during
376
chloramination were basically the same as those during chlorination, but the
377
corresponding reaction time was much longer. In summary, the degradation pathways
378
of iopamidol during chlor(am)ination were proposed and exhibited in Fig. 5.
SC
M AN U
TE D
EP
380
3.3.2. DBPs formation
381
AC C
379
RI PT
364
As illustrated in Section 3.3.1, the deiodinated, hydroxylated and chlorinated
382
products of iopamidol during chlorination and chloramination might form and
383
facilitate the subsequent attack by oxidants in DBPs formation. Meanwhile, the
384
gradual deiodination of iopamidol would lead to the release of iodide in solution
385
(Steger-Hartmann et al., 2002; Doll and Frimmel, 2004; Jeong et al., 2010; Tian et al.,
386
2014), which can be further oxidized to HOI (Richardson et al., 2012) and lead to the
387
formation of iodinated DBPs. Therefore, the regular DBPs and iodinated DBPs
16
ACCEPTED MANUSCRIPT 388
formation during chlor(am)ination was measured, and the results were summarized in
389
Table 1. As exhibited in Table 1, regular DBPs (including chloroform (CF),
391
dichloroacetonitrile (DCAN), trichloroacetic acid (TCAA) and dichloroacetic acid
392
(DCAA)) and iodinated DBPs (including CHCl2I and CHClI2) were detected during
393
iopamidol chlorination. DCAN, DCAA and TCAA constituted the majority of regular
394
DBPs, which may be related to the comparatively stronger oxidation capacity of
395
chlorine upon the peptide groups of iopamidol (Hong et al., 2009). CHCl2I was the
396
main iodinated DBPs while no CHI3 was measured. The CHO cell chronic
397
cytotoxicity data also clearly indicated that chlorination of iopamidol generated a
398
toxic mixture of DBPs (Wendel et al., 2014). The DBPs especially iodinated DBPs
399
(CHCl2I and CHClI2) might be responsible for the enhanced toxicity of the
400
chlorinated iopamidol solution.
M AN U
SC
RI PT
390
The regular DBPs detected during iopamidol chloramination include trace
402
DCAN but no haloacetic acids due to the weaker oxidation capability of chloramines
403
than chlorine. The findings that chloramination produced significantly less regular
404
DBPs than chlorination agreed well with former studies (Guay et al., 2005; Bougeard
405
et al., 2010). However, the chloramination of iopamidol led to the formation of
406
slightly higher iodinated DBPs, remarkable CHI3, but much less CHCl2I and CHClI2
407
compared to those during chlorination. The organoleptic threshold concentration of
408
CHI3 is the lowest in all of the iodinated DBPs, which lies between 0.03 and 1.0 µg
409
L-1 (Cancho et al., 2001). Therefore, the risk of CHI3-related problems was highly
410
enhanced during chloramination of waters containing iopamidol.
AC C
EP
TE D
401
411
The formation of iodinated DBPs was due to the oxidation of iodide by chlorine
412
and chloramines (Bichsel and von Gunten, 1999; 2000). The enhanced formation of
17
ACCEPTED MANUSCRIPT 413
iodinated DBPs and induction of CHI3 during chloramination were in agreement with
414
other studies (Bichsel and von Gunten, 1999; 2000). It is also inferred from Table 1
415
that the iodine conversion from iopamidol to iodinated DBPs distinctly increased by
416
40% during chloramination compared to that during chlorination.
418
RI PT
417
3.4. Practical Implications
Iopamidol, the most frequently detected ICM, was also reported to be the most
420
important contributor to the formation of highly toxic iodinated DBPs among the
421
investigated ICM (Duirk et al., 2011). However, due to the structure stability and
422
nontoxicity, the features of iopamidol during chlor(am)ination are not fully
423
understood yet. However, it was evident from the pH effect in this study that the
424
degradation of iopamidol by chlor(am)ine might be highly favored in real waters at
425
circumneutral pHs (Figs. 2 and 4).
M AN U
SC
419
The unified degradation pathways of iopamidol during chlori(am)nation
427
provided a deep insight on the transformation of this triiodinated compound to
428
iodinated DBPs. Highly toxic iodinated DBPs, especially CHI3, were formed during
429
chloramination, which greatly enhanced the toxicity of the disinfected waters.
430
Therefore, the disinfection risk of chloramines should be concerned for waters
431
polluted with iopamidol. Moreover, the results obtained here were from the
432
experiments conducted in purified water in the absence of NOM. Further research
433
regarding the effects of NOM on iopadimal chlor(am)ination as well as iodinated
434
DBPs formation should be explored so as to adopt feasible technology for the control
435
these highly toxic DBPs in drinking water treatment processes.
AC C
EP
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426
436 437
4. Conclusions
18
ACCEPTED MANUSCRIPT 438
(1) The chlorination kinetics of iopamidol can be described by a second-order Cl2 k app
model, first-order in iopamidol and first-order in chlorine concentrations. The
440
significantly increased with solution pH. The reaction rate constants of iopamidol
441
with HOCl and OCl- were 1.66±0.09×10-3 M-1 s-1 and 0.45±0.02 M-1 s-1, respectively.
442
RI PT
439
(2) The chloramination of iopamidol fitted third-order kinetics, second-order in NH 2Cl k app reached a
iopamidol and first-order in chloramine concentrations. The
444
maximum at pH 7 but lowered evidently in both alkaline and acidic conditions. It was
445
thus inferred that the free chlorines can degrade iopamidol effectively while the
446
combined chlorines can not.
M AN U
SC
443
(3) The main intermediates during chlor(am)ination of iopamidol were identified
448
using UPLC-ESI-MS. The degradation pathways were characterized, including
449
stepwise deiodination accompanied by the addition of hydroxyl groups and chloro
450
atoms at the iodo sites on the aromatic ring of iopamidol.
TE D
447
451
(4) Regular DBPs (including CF, DCAN, TCAA and DCAA) and iodinated
452
DBPs (including CHCl2I and CHClI2) were measured during chlorination of
453
iopamidol.
454
chloramination. The iodine conversion to iodinated DBPs distinctly increased during
455
chloramination compared with that during chlorination.
457
formation
was
remarkable
during
iopamidol
EP
CHI3
AC C
456
However,
Acknowledgments
458
This study was supported in part by the Natural Science Foundation of China
459
(No. 51678354 and 51478323), State Key Laboratory of Pollution Control and
460
Resource Reuse Foundation in China (No. PCRRK16005), the National Major
461
Science and Technology Project of China (No. 2015ZX07406004) and the Ministry of
462
Science and Technology in Taiwan (and 104-2221-E-327-001-MY3). 19
ACCEPTED MANUSCRIPT 463
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EP
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ACCEPTED MANUSCRIPT 523
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538
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TE D
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EP
541
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Jeong, J., Jung, J., Cooper, W.J., Song, W., 2010. Degradation mechanisms and kinetic 22
ACCEPTED MANUSCRIPT 553
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554
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556
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557
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558
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555
Losito, H., Zambonin, C.G., Palmisano, F., 2000. Degradation of chlortoluron in water disinfection processes: a kinetic study. J. Environ. Monitor. 2, 582-586.
Mitch, W.A., Sedlak, D.L., 2002. Formation of N-nitrosodimethylamine (NDMA)
562
from dimethylamine during chlorination. Environ. Sci. Technol. 36, 588-595.
563
Munch, D., Hautman, D., 1995. Method 551.1: Determination of Chlorination Byproducts,
M AN U
SC
561
564
Disinfection
565
Pesticides/Herbicides in Drinking Water by Liquid-Liquid Extraction and Gas
566
Chromatography
567
Determination of organic compounds in drinking water.
with
Chlorinated
Electron-Capture
Solvents,
Detection.
and
Halogenated
Methods
for
the
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648
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649
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26
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Table Table 1. Formation of regular and iodinated DBPs during chlorination and chloramination of iopamidol a Oxidation process
CF
22.23 ± 1.41 b
DCAN
221.27 ± 5.66
DCAA
55.85 ± 0.66
TCAA
302.63 ± 6.36
CHCl2I
154.62 ± 4.36
CHClI2
35.14 ± 3.76
12.02 ± 2.42
CHI3
ND
168.47 ± 13.45
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Iodinated DBPs
Chloramination
iodine conversion to iodinated DBPs (%) d Notes:
ND c
5.55 ± 1.43 ND
ND
6.24 ± 1.86
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Regular DBPs
Chlorination
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Detected DBPs (µg -1 L)
3.22 ± 0.04
4.64 ± 0.25
Contact time 7 d for chlorination or chloramination of iopamidol.
b
The standard deviation was obtained from triplicate measurements.
c
ND = Not-detected.
d
Iodine conversion from iopamidol to iodinated DBPs was calculated as the total
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a
iodine molar quantity of iodinated DBPs divided by the initial concentration of
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iodine in iopamidol (30 µM).
ACCEPTED MANUSCRIPT List of Figure Captions Fig. 1. Pseudo-first-order kinetics plot of iopamidol chlorination and the relationship of
Cl2 k obs to [HOCl ]T at 25 ±1oC, pH 7, [iopamidol]0 = 5 µM, [phosphate buffer] =
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10 mM and five different chlorine dosages. Cl
Fig. 2. Effect of pH on the apparent second-order rate constant ( k app2 ) of iopamidol chlorination. ([buffer] = 10 mM, [iopamidol]0 = 5 µ M, [Cl2]0 = 200 µM)
NH 2Cl k obs to [ NH 2 Cl ]T at 25 ±1oC, pH 7, [iopamidol]0 = 5 µM,
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relationship of
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Fig. 3. Pseudo-second-order kinetics plot of iopamidol chloramination and the
[phosphate buffer] = 10 mM and four different chloramine dosages. NH Cl
Fig. 4. Effect of pH on the apparent third-order rate constant ( k app 2 ) of iopamidol chloramination. ([buffer] = 10 mM, [iopamidol]0 = 5 µ M, [NH2Cl]0 = 250 µM)
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chloramination.
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Fig. 5. Proposed degradation pathways of iopamidol during chlorination or
ACCEPTED MANUSCRIPT 6.94 x10-5 5.56
obs
kCl2 (s-1)
5
4.2 2.78
4
0 0
3
200
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ln(C 0/C t)
1.39
400 600 [Cl ] (µM) 2 0
800
1000
2
[Cl2]0=50µ M, R =0.996 2
[Cl2]0=100µ M, R =0.998
2
2
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[Cl2]0=200µ M, R =0.997 2
[Cl2]0=500µ M, R =0.994
1
2
0
0
8
16
24
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[Cl2]0=1000µ M, R =0.998
32
40 48 56 Time (h)
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Fig. 1
64
72
80
88
96
ACCEPTED MANUSCRIPT 1
0.5 HClO 0.42
-1
-1
kapp (M s )
0.33 0.6
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Cl2
Molar fraction
0.8
0.4
0.17
0.2
5
6
7 pH
8
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0
SC
0.083
-
ClO
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Fig. 2
9
0
ACCEPTED MANUSCRIPT 4.17 x10-3 2.78
obs
kNH2Cl (M -2 s-1)
2
1.5
0
1
0
200
RI PT
-1
1/Ct-1/C0 (M )
1.39
400 600 NH Cl (µM) 2
800
2
[NH 2Cl]0=50µ M, R =0.997 2
[NH 2Cl]0=100µ M, R =0.994
0.5
2
SC
[NH 2Cl]0=250µ M, R =0.985 2
[NH 2Cl]0=1000µ M, R =0.994
0
48
96
144 192 Time (h)
240
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0
AC C
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Fig. 3
288
336
1000
ACCEPTED MANUSCRIPT 1
8.33 NH2Cl
6.94
-2 NH2Cl
kapp
4.17
0.4
NHCl2
2.78
0.2
5
6
7 pH
SC
1.39
8
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0
-1
5.56 0.6
(M s )
0.8
-3
RI PT
Proportional distribution
X10
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Fig. 4
9
0
ACCEPTED MANUSCRIPT HO O I O CH 3 NH OH
OH NH I NH I
OH
HO O
deiodination CH3
OH
NH I
OI
NH OH
NH
O
OH Iopamidol(M=777)
O 651
OH
OH
addition of Cl HO O I CH3 O
OH NH I NH Cl O
OH
CH 3 OH
NH Cl O
OH
OH
595
CH 3 NH Cl O 561
OH
Cl O 576.5
OH
NH
O
CH 3 O
NH
OH
NH
Cl O 434.5
OH
OH NH OH NH
HO O
OH
HO O
OH
substitution of I by OH
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deiodination
CH3
OH
NH
OH
NH OH
OI
SC
CH 3
NH
OI
OH NH OH NH
HO O
OH
HO O
NH Cl NH
OI
substitution of I by OH
deiodination
OH
HO O
OH
Cl 686.5
substitution of I by Cl
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OH
NH
OH
OH
NH
OH
Cl O 450.5
OH
addition of Cl
substitution of I by Cl
OH
NH
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HO O Cl O CH3 NH
OH
NH
Cl O 469
addition of OH OH OH
addition of OH
OH NH Cl NH
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HO O Cl CH 3 O
OH
NH
Cl O
AC C
OH
HO O Cl CH3 O
503.5
OH
OH NH OH NH OH
NH OH
HO O OH CH 3 O
Cl O 485
OH
Further degradation products
Fig. 5
OH NH OH NH OH
NH OH
Cl O 467
OH
ACCEPTED MANUSCRIPT Highlights The chlorination kinetics of iopamidol can be described by a second-order model. Iopamidol chlorination significantly increased with solution pH. NH 2Cl k obs
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Iopamidol chloramination fitted third-order model and maximum occurred at pH 7.
The destruction pathways of iopamidol by chlor(am)ination were proposed.
SC
More iodinated DBPs especially CHI3 was formed in chloramination than
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chlorination.
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