Comparative study on degradation of propranolol and formation of oxidation products by UV/H2O2 and UV/persulfate (PDS)

Article abstract of DOI:10.1016/j.watres.2018.08.074

The frequent detection of propranolol, a widely used β-blocker, in wastewater effluents and surface waters has raised serious concern, due to its adverse effects on organisms. UV/hydrogen peroxide (UV/H₂O₂) and UV/persulfate (UV/PDS) processes are efficient in eliminating propranolol in various waters, but the formation of oxidation products in these processes, as well as the assessment of their toxicity, has not been systematically addressed. In this study, we identified and compared transformation products of propranolol produced by hydroxyl radical (^?OH) and sulfate radical (SO₄^?-). The electrostatic attraction enhances the reaction between SO₄^?- and the protonated form of propranolol, while ^?OH shows non-selectivity toward both protonated and neutral propranolol species. The hydroxylation of propranolol by ^?OH occurs at either amine moiety or naphthalene group while SO₄^?- favors the oxidation of the electron-rich naphthalene group. Further oxidation by ^?OH and SO₄^?- results in ring-opening products. Bicarbonate and chloride exert no effect on propranolol degradation. The generation of CO₃^?- and Cl-containing radicals is favorable to oxidizing naphthalene group. The acute toxicity assay of Vibrio fischeri suggests that SO₄^?- generates more toxic products than ^?OH, while CO₃^?- and Cl-containing radicals produce similar toxicity as SO₄^?-. High concentrations of bicarbonate in UV/H₂O₂ increase the toxicity of treated solution.

Full text of DOI:10.1016/j.watres.2018.08.074

Accepted Manuscript
Comparative study on degradation of propranolol and formation of oxidation products
by UV/H O and UV/persulfate (PDS)
2 2
Yi Yang, Ying Cao, Jin Jiang, Xinglin Lu, Jun Ma, Suyan Pang, Juan Li, Yongze Liu,
Yang Zhou, Chaoting Guan
PII:
S0043-1354(18)30704-8
https://doi.org/10.1016/j.watres.2018.08.074
WR 14050
DOI:
Reference:
To appear in: Water Research
Received Date: 12 April 2018
Revised Date: 22 July 2018
Accepted Date: 31 August 2018
Please cite this article as: Yang, Y., Cao, Y., Jiang, J., Lu, X., Ma, J., Pang, S., Li, J., Liu, Y.,
Zhou, Y., Guan, C., Comparative study on degradation of propranolol and formation of oxidation
products by UV/H O and UV/persulfate (PDS), Water Research (2018), doi: https://doi.org/10.1016/
2 2
j.watres.2018.08.074.
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ACCEPTED MANUSCRIPT
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Comparative study on degradation of propranolol and
formation of oxidation products by UV/H2O2 and
UV/persulfate (PDS)
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Submitted to
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Water Research
Yi Yang1, Ying Cao1, Jin Jiang1,*, Xinglin Lu1,*, Jun Ma1, Suyan Pang2, Juan
Li1, Yongze Liu3, Yang Zhou1, Chaoting Guan1
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1 State Key Laboratory of Urban Water Resource and Environment,
Harbin Institute of Technology, Harbin 150090, China
2 School of Municipal and Environmental Engineering, Jilin Jianzhu University,
Changchun 130118, China
3 School of Environmental Science and Engineering, Beijing Forestry University,
Beijing 100083, China
*Corresponding authors:
* E-mail: jiangjinhit@126.com (J. Jiang); xinglin.lu@yale.edu (X. Lu)
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22 ABSTRACT.
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The frequent detection of propranolol, a widely used β-blocker, in wastewater effluents and
surface waters has raised serious concern, due to its adverse effects on organisms.
UV/hydrogen peroxide (UV/H2O2) and UV/persulfate (UV/PDS) processes are efficient in
eliminating propranolol in various waters, but the formation of oxidation products in these
processes, as well as the assessment of their toxicity, has not been systematically addressed.
In this study, we identified and compared transformation products of propranolol produced
•-
by hydroxyl radical (•OH) and sulfate radical (SO4 ). The electrostatic attraction enhances the
•-
•
reaction between SO4 and the protonated form of propranolol, while OH shows non-
selectivity toward both protonated and neutral propranolol species. The hydroxylation of
•
•-
propranolol by OH occurs at either amine moiety or naphthalene group while SO4 favors
•
•-
the oxidation of the electron-rich naphthalene group. Further oxidation by OH and SO4
results in ring-opening products. Bicarbonate and chloride exert no effect on propranolol
•-
degradation. The generation of CO3 and Cl-containing radicals is favorable to oxidizing
•-
naphthalene group. The acute toxicity assay of Vibrio fischeri suggests that SO4 generates
•
•-
more toxic products than OH, while CO3 and Cl-containing radicals produce similar
•-
toxicity as SO4 . High concentrations of bicarbonate in UV/H2O2 increase the toxicity of
treated solution.
Keywords: propranolol; hydroxyl radical; sulfate radical; carbonate radical; Cl-containing
radicals;
transformation
products
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46 1. Introduction.
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As an important class of pharmaceuticals, β-blockers bind to the β-adrenergic receptors
in human body and block the action of epinephrine and norepinephrine, which are used to
treat cardiac malfunctions.(Khetan and Collins 2007) This target effect of β-blockers to fish
with β-adrenergic receptors may exert a similar response to other vertebrates.(Huggett et al.
2002b) β-blockers also exhibit specific nontarget effects on organisms. For example, a
previous study demonstrated that three types of β-blocker could inhibit photosynthesis
efficiency of a green algae (Desmodesmus subspicatus), as echoed by EC50 values of 4.1, 40
and 1335 mg/L for propranolol, metoprolol, and atenolol, respectively.(Escher et al. 2006)
Another study also indicated the influence of propranolol on the steroid level and
reproduction in medaka (Oryzias latipes) with exposure to 0.5 µg/L propranolol.(Huggett et
al. 2002a) These results suggest that propranolol is more toxic to organisms than other β-
blockers. The additive effect of propranolol, which extensively exists in β-blockers mixtures,
could contribute to the major toxic potential of overall compounds in the aquatic environment
even at low concentrations.(Cleuvers 2005) Additionally, the growing consumption of
propranolol in medication and its insufficient removal by conventional WWTPs lead to
increasing occurrence of propranolol in surface waters, thereby conceiving substantial
concern of its toxicity to aquatic organisms.(Kostich et al. 2014) (Wang et al. 2015)
Advanced oxidation processes (AOPs) are effective in removal of
pharmaceuticals.(Keen and Linden 2013, Wols and Hofman-Caris 2012, Zhang et al. 2015)
Conventional AOPs typically involve the formation of hydroxyl radicals (•OH) as an
oxidizing species to destruct recalcitrant organic contaminants in drinking water sources and
wastewaters. Recently, sulfate radical-based AOPs have received increasing research
•-
interests, as the rate constants for the reaction of sulfate radical (SO4 ) with many organic
•
contaminants are near diffusion-limited rate constants.(Neta et al. 1988) Compared to OH,
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the benefit of SO4 is its less reactivity to scavengers like bicarbonate and dissolved organic
•
carbon (DOC), which substantially decrease the efficiency of OH-based AOPs through
•
consuming a large portion of OH.(Buxton et al. 1988, Yang et al. 2015) The presence of
•
bicarbonate and halides at high concentrations becomes important scavengers of OH and
•-
•
•-
SO4 to generate daughter reactive species. Unlike OH, SO4 favors the conversion of
halides to halogen reactive species at neutral pH.(Anipsitakis et al. 2006, Yang et al. 2014)
The modeling results showed that inorganic radical concentrations in many wastewaters
exceeded those of •OH and SO4 , especially for CO3 , by several orders of
•-
•-
magnitude.(Grebel et al. 2010, Yang et al. 2014, Zhang et al. 2015) Some halogen reactive
•-
•-
•
•-
species (e.g., Cl2 ) and CO3 are more selective oxidants than OH and SO4 , but they are
capable of oxidizing some organic contaminants.(Beitz et al. 1998, Canonica et al. 2005,
Hasegawa and Neta 1978) For instance, our previous results indicated higher reactivity of
•-
CO3 and halogen reactive species toward propranolol, which led to efficient removal of
propranolol by AOPs in various waters.(Yang et al. 2016)
•
The transformation of propranolol and its product formation by OH-based AOPs (e.g.,
ozone or photocatalytic by TiO2) have been well documented, where hydroxylation and ring-
opening are the major reaction pathways.(Benner and Ternes 2009, Santiago-Morales et al.
2013, Song et al. 2008) Nevertheless, little study has investigated the transformation of
•-
•
•-
propranolol by SO4 -based AOPs. The different reactivity between OH and SO4 in the
formation and the yield of different products have been demonstrated in the transformation of
diclofenac and sulfamethoxazole.(Mahdi Ahmed et al. 2012, Yang et al. 2017, Yu et al. 2013)
•-
In these cases, SO4 reacts with amine moieties to form corresponding hydroxylamine and
•
nitro moieties, which were not observed in the reaction of OH. Due to the poor
mineralization in most applied AOPs, the difference in products formation between these two
processes resulted in the discrepancy in toxicity assay.(Yang et al. 2017) Therefore, it is
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critical to provide a fundamental understanding of the transformation of propranolol in these
AOPs, as well as the toxicity of the formed products, thereby facilitating the application of
these AOPs in oxidizing propranolol.
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This study aims to compare the transformation of propranolol by OH-based or SO4 -
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based AOPs. The rate constants for the reaction of OH and SO4 with propranolol are
determined at different pHs. The transformation products are identified to elucidate the
reaction pathways. We for the first time systematically compare the effect of bicarbonate and
chloride on products formation of propranolol in these two AOPs. The efficiency of
propranolol degradation is also evaluated in two authentic water matrices, while reactive
species involved in reactions are predicted by kinetic modeling. Vibrio fisheri is used in
toxicity assay, which is conducted under various operating conditions to evaluate the toxicity
of the products in both AOPs.
109 2. Materials and methods.
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2.1. Materials.
Propranolol and ammonium acetate were purchased from Sigma-Aldrich. Sodium
perdisulfate (PDS), H2O2 solution (35% w/w), tert-butanol, sodium chloride and sodium
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bicarbonate were received from Sinopharm Chemical Reagent Co. Ltd., China. Methanol and
acetic acid in HPLC grade were obtained from Thermo Fisher Scientific, and acetonitrile was
received from Merck. Stock solutions were prepared in deionized (DI) water (18.2 MΩ/cm)
from a Milli-Q purification system (Millipore, Billerica, MA).
2.2. Experimental procedures.
A collimated beam apparatus, consisting of four low-pressure mercury lamp (254 nm, 10
W, GPH212T5L/4, Heraeus) positioned at 30 cm shining down onto a 100 mL crystallization
dish (pathlength = 4.0 cm), was used for photolysis experiments, as described previously.(Liu
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et al. 2015) The incident photonic flux at 254 nm was 1.291 × 10-7 Einstein L-1 s-1, which was
determined by the iodide-iodate chemical actinometer.(Rahn et al. 2003) Except when
otherwise mentioned, the solution contained PDS or H2O2 at 1 mM and propranolol at 20 µM,
and was buffered with 10 mM phosphate. Samples (1 mL) were periodically withdrawn and
supplemented with 20 µL methanol to quench any radical formed by thermolysis of PDS or
H2O2, and kept at 4 °C for further analysis within 12 h. Experiments were conducted at 20 ±
2 °C.
•
•-
The second-order rate constants of propranolol with OH and SO4 were determined by
competition kinetics. Atrazine was used as a reference compound for •OH and SO4•- reactions
with k ꢀꢁ,ꢂꢃꢄ = 2.6 × 109 M-1 s-1 and kꢅꢀ ,ꢂꢃꢄ = 2.6 × 109 M-1 s-1, respectively.(Yang et al.
∙
∙ꢇ
ꢆ
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2015) Experiments were conducted according to the aforementioned, except that both
propranolol and atrazine were spiked at 5 µM. For the determination of second-order rate
•-
constant with SO4 , 10 mM tert-butanol was added to quench •OH in UV/PDS.
Some experiments were conducted using real water samples (i.e., surface water and
groundwater) from two drinking water treatment plants. These water samples were filtered
through a glass fiber filter (0.7 µm, Whatman) and stored at 4°C. The surface water sample
had a low DOC and low alkalinity (DOC 3.8 mg/L, alkalinity 0.2 mM, [Cl-] = 5.2 mg/L, pH
7.2), while the groundwater sample has relatively higher DOC and alkalinity (DOC 6.9 mg/L,
alkalinity 8.0 mM, [Cl-] = 7.2 mg/L, pH 7.6). Water samples were buffered using 2 mM
phosphate. All experiments were conducted in duplicate, and the average values and standard
deviations were presented.
•-
2.3. Determination of rate constants for the reactions of propranolol with •OH and SO4 .
The degradation rate of propranolol by direct photolysis was negligible at pH range of
8–11 in UV/H2O2 and UV/PDS (Supplementary data, Fig. S1). To evaluate the specific rate
•
•-
constants for the reactions of OH and SO4 with the protonated and the neutral form of
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k
k
app,SO•4-
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propranolol, the apparent rate constants (
and
) were determined using
app, • OH
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competition kinetics at pH ranging from 8 to 11, according to the methods described in Text
S1. The initial rate of propranolol and atrazine degradation (degraded fraction of each
compound < 20%) was used for calculation to circumvent the competitive effect of their
kapp, • OH
k
app,SO•4-
products. The measured
speciation of propranolol:
and
can be expressed as incorporating acid-base
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kapp, • OH = α
k
+αSHkSH,• OH
(1)
SH+2 SH+2 , • OH
k
= α
k
+ αSHk
153
(2)
app,SO•4-
SH+2 SH+2 ,SO•4-
SH,SO•4-
+
α
α
SH
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155
156
where
and
are the equilibrium distribution coefficients of protonated (SH2 ) and
SH+2
neutral (SH) forms at a given pH, respectively, and calculated from acidity constant pKa
kSH,• OH
k
k
k
and
SH,SO•4-
9.5.(Benner and Ternes 2009)
,
,
are the second-order
SH+2
,
• OH
•
SH+2 ,SO•4-
•-
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rate constants for the reactions of OH and SO4 with protonated and neutral forms,
respectively. The specific rate constants were calculated through nonlinear regression of
experimental data.
2.4. Analytical methods.
Propranolol and atrazine were analyzed by a Waters 1525 HPLC with a Waters 2487
dual λ detector. Chromatographic separations were performed using a Waters Symmetry C18
column (150 mm × 4.6 mm, 5 µm). The concentrations of propranolol and atrazine were
quantified at λ = 285 nm and λ = 260 nm, respectively, with an eluent of 0.1% acetic acid and
methanol with a ratio of 30:70 (v/v) at a flow rate of 1 mL/min.
Identification of products of propranolol was performed through molecular mass, which
was determined by a triple quadrupole TOF mass spectrometer (Triple TOF 5600, AB Sciex)
coupled with the Ekspert ultralLC110. A Poroshell 120 EC-C18 column (50 mm × 3.0 mm,
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2.7 µm) was used as chromatographic separation. Accurate MS and MS/MS patterns of
propranolol and its transformation products were analyzed in both positive and negative
electrospray ionization (ESI) modes. The experimental conditions of chromatographic
separation and instrumental parameters for HPLC/ Triple TOF are provided in Text S2.
2.5. Kinetic simulations in water samples.
Kinetic modeling of radical concentration for UV/H2O2 and UV/PDS processes in two
authentic waters was performed using a computer program, Kintecus V6.01.(Ianni 2016)
Over one hundred rate constants of elementary reactions were obtained from the literature
(Table S3).(Das et al. 1999, Yang et al. 2014, 2016) Due to the lack of sufficient rate
constants of many radicals with propranolol, the modeling only took into account the effects
of chloride, bicarbonate, and DOC.
2.6. Toxicity analysis.
The acute toxicity assay was carried out by measuring the decrease in the
bioluminescence of Vibrio fischeri.(Fernández-Alba et al. 2002, Wu et al. 2016, Yang et al.
2017) The measurements were performed using a Promega GloMax®-Multi Jr. The
luminescent intensity was determined to calculate the inhibition after 30 min.
186 3. Results and discussions.
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3.1. Oxidation kinetics of the reaction of propranolol with •OH and SO4 .
The phototransformation quantum yield Φ254 of propranolol was determined to be 8.93 ×
10-3 at pH 8.3 in our previous study.(Yang et al. 2017) The molar absorption and quantum
yield of propranolol were not varied with pH. The photophysical property of propranolol was
attributed to the chromophore structure of naphthalene group, which was unlikely affected by
pH.(Liu and Williams 2007, Sortino et al. 2002)
•
k
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The reaction rate constant of propranolol with OH ( app, • OH ) was independent of pH
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•
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from 8 to 11 (Fig. 1A), indicating that OH exhibited comparable reactivity to both neutral
k
k
and anionic forms of propranolol. Therefore, the same value of
• OH and
,
were
SH,• OH
SH+2
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suggested here and determined to be (1.26 ± 0.10) × 1010 M-1 s-1, which was consistent with
the value of (1.07 ± 0.02) × 1010 M-1 s-1 reported in radiolysis experiments.(Song et al. 2008)
•
This value is also comparable to the rate constants determined for the reaction of OH with
naphthalene (9–12 × 109 M-1 s-1).(Buxton et al. 1988) These results indicated that the reaction
•
of OH with naphthalene group was predominant, with minimal contribution from the side
chain group.
•-
Sulfate radical is an electrophile so that a faster rate constant for the reaction of SO4
k
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with the neutral form of propranolol is expected. However, a continuous decrease in
app,SO•4-
k
k
SH,SO•4-
with increasing pH from 8 to 11 was observed in Fig. 1B, where
and
was
SH+2 ,SO•4-
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determined to be (3.21 ± 0.08) × 1010 M-1 s-1 and (1.39 ± 0.10) × 1010 M-1 s-1, respectively.
•-
Steenken et al. reported that the second-order rate constant for SO4 with naphthalene is 2.9 ×
109 M-1 s-1.(Steenken et al. 1990) The higher rate constant for propranolol may be ascribed to
•-
the following two aspects. Due to the electrophilicity of SO4 , electron-donating substituents
like methoxy or hydroxy groups can cause a significant increase in rate constants, which has
been demonstrated for substituted benzenes and benzoate ions.(Neta et al. 1977) Therefore,
naphthalene substituted by alkoxy group ((CH3)2CNHCH2CH(OH)CH2O–) increases the
•-
reactivity of the naphthalene moiety with SO4 . Additionally, we noticed that these two
values approached the diffusion-controlled limit, suggesting that the difference between the
expected and the experimental data was likely resulted from the electrostatic attraction
•-
between the negatively charged SO4 and the positively charged protonation form of
•-
propranolol. A previous study also reported that the electrostatic repulsion between SO4
with the anionic form of organic compounds resulted in lower reaction rate constants than
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with the neutral form.(Neta et al. 1977)
3.2. Effect of bicarbonate.
•
•-
Bicarbonate is an important scavenger of OH and SO4 in the aqueous phase to form
•-
carbonate radical (CO3 ) (reactions 3 and 4).(Anastasio and Matthew 2006, Grebel et al.
2010, Yang et al. 2014) Fig. 2 exhibits the effect of bicarbonate on the degradation of
propranolol in UV/H2O2 and UV/PDS. No difference in propranolol degradation for
UV/H2O2 was observed as the increase of bicarbonate concentration up to 500 mM. The
presence of 5 and 50 mM bicarbonate in UV/PDS showed negligible impact on propranolol
degradation kinetics as well, while a marginal decline was observed with the addition of 500
•
•-
mM bicarbonate. Based on the calculation, 94.5% of OH and 70% of SO4 were scavenged
•-
by 500 mM bicarbonate respectively to form CO3 . Lian et al. reported that the rate constant
for the reaction of CO3•- with propranolol was 1.42 × 107 M-1 s-1.(Lian et al. 2017) Although
•
this rate constant is three orders of magnitude lower than those for reaction with OH and
•-
•-
SO4 , the concentration of CO3 appeared to be high enough to fully compensate for the
decreased contribution of •OH and SO4 to the degradation of propranolol.
•-
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HCO3− + OH → CO3− + H2O
k = 8.5 × 106 M-1 s-1
(3)
(4)
HCO3− +SO4− → CO3− + HSO−4 k = 2.8 × 106 M-1 s-1
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3.3. Effect of chloride.
Chloride is widely present in drinking water and wastewater with various concentrations.
•
•-
The reaction of OH and SO4 with Cl- generates reactive Cl-containing radicals (e.g., Cl•,
•-
Cl2 and ClOH•-). Kinetic modeling in previous studies demonstrated different formation
pathways of reactive Cl-containing radicals in UV/H2O2 and UV/PDS (Grebel et al. 2010,
Yang et al. 2014). The reaction of OH with Cl- has a fast rate constant of reverse reaction
•
(reaction 5), where Cl• forms at low pH (reaction 6).(Yang et al. 2014) In contrast, the fast
•-
reaction between SO4 and Cl- forms Cl• directly (reaction 7), which can further react with
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Cl- to form other Cl-containing radicals. Since the reaction of •OH with Cl- was negligible in
UV/H2O2 at pH 8, (Yang et al. 2016) the effect of Cl- was only investigated in UV/PDS.
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Cl− + OH → ClOH − + H2O
ClOH − +H+ → Cl + H2O
Cl− +SO4− → Cl +SO42−
kfor = 4.3 × 109 M-1 s-1; krev = 6.1 × 109 M-1 s-1
(5)
kfor = 2.1 × 1010 M-1 s-1
kfor = 3.0 × 108 M-1 s-1
(6)
(7)
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No significant inhibition of propranolol degradation was observed with Cl- concentration
•-
ranging from 0.1 to 100 mM. In the presence of 100 mM Cl-, 98% of SO4 was scavenged,
where Cl-containing radicals were the predominant pathway of propranolol degradation. Cl•
•-
•-
and Cl2 radicals are strong oxidants (E E
(Cl•/Cl-) = 2.4 V and (Cl2 /2Cl-) = 2.0 V)(Martire et
al. 2001) and likely to react with organic compounds.(Hasegawa and Neta 1978) The second-
order rate constants for the reaction of Cl• with organic compounds were reported comparably
•-
•-
•-
to those of •OH and SO4 .(NIST) Although Cl2 was more selective than •OH and SO4 (rate
constants of 105–109 M-1 s-1),(NIST) the concentration of Cl2 could exceed those of •OH and
•-
•-
SO4 by several orders of magnitude,(Yang et al. 2016) which contributed to the degradation
of propranolol.
3.4. Identification of transformation products.
Eleven transformation products (TPs) belonging to nine nominal masses were detected
and identified using ESI-TOF-MS. The accurate m/z values are provided in Table 1. The
product ion spectra and the fragmentation pathways of propranolol ([M + H]+ = 260.1649)
were illustrated in Fig. S2. The m/z 183 fragment ion was resulted from the loss of
isopropene, ammonia and water. Fragment ions m/z 155 and m/z 157 corresponded to the
cleavage on the side chain and rearrangement of the C–O moiety, which exhibited an
unchanged naphthalene group. The m/z 116, 98 and 74 fragment ions were formed by the
different cleavages of the side chain. These characteristic fragments of propranolol were
important for the comparison with the spectra of TPs as they provide information on the
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status of functional groups after oxidation. For structural elucidation, the fragmentation
pathways of TPs were investigated by performing product ion scans, which were provided in
Fig. S3–S13.
3.4.1. Hydroxyl radical.
Hydroxylation. Due to the negligible degradation of propranolol by direct photolysis, all
the nine TPs detected in UV/H2O2 were ascribed to the oxidation by •OH. The observation of
two isomers of TP 275 ([M + H]+ = 276.1594) was owing to the addition of one oxygen atom
to propranolol molecule. The product ion scan of TP 275-1 showing two sequential loss of
water (fragment ions m/z 258 and 240) could signify two hydroxyl moieties, which were
present next to a removable proton. This result implied that amine moiety was likely
hydroxylated to form a hydroxylamine product. The fragment ion m/z 173 of TP 275-2 was
formed through hydroxylation on naphthalene group of m/z 157, thereby indicating the
oxidation of the naphthalene group on propranolol. The occurrence of m/z 116 and 98
fragment ions provided further support on the proposed fragment pathway. The difference in
molecular weight of propranolol and TP 291-1 ([M + H]+ = 292.1543) was 32 Da,
corresponding to the addition of two oxygen atoms. The loss of 60 Da (i.e., 18 + 42 Da)
suggested the cleavage of water and isopropyl moiety. Double hydroxylation on the ring was
supported by the fragment ion m/z 175, corresponding to the cleavage of C–O moiety and
two hydroxylated groups on the ring.
Ring-opening. Several peaks with a nominal mass of 307 Da were observed. TP 307 ([M
+ H]+ = 308.1492) was resulted from the addition of three oxygen atoms (+48 Da) to
propranolol. The product ion scan showing two sequential loss of water (fragment ions m/z
290 and 272) signified that two hydroxyl moieties were present next to a removable proton,
implying one hydroxylation on the side chain. Hydroxylation next to either ethoxy group or
amine moiety would cause an unstable hemiaminal.(Benner and Ternes 2009) Hence, the
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amine moiety was likely hydroxylated, thus leading to the formation of hydroxylamine. The
m/z 175 fragment ion corresponded to the addition of two oxygen atoms on the naphthalene
group. The proposed formation of two aldehyde moieties rather than a double hydroxylation
was supported by the fragment ion m/z 131 (175-131=44 Da, loss of CO2). The structure of
TP 281 ([M + H]+ = 282.1336) was also a ring-opening product with the occurrence of m/z
149, indicating the formation of two aldehyde moieties. Only one loss of water (fragment ion
m/z 264) confirmed the hydroxylation of the naphthalene group. TP 293 ([M + H]+ =
294.1700) showed one less double bond than TP 291-1. The unchanged side chain can be
seen by the single loss of water (fragment ion m/z 276). The fragment ions m/z 199 and m/z
173 had quinone-like structure, which derived from dehydration of one aldehyde moiety and
one hydroxyl group in the aromatic structure. TP 309 ([M + H]+ = 310.1649) showed two
isomers. The fragment ion m/z 177 was resulted from the cleavage of the C-O bond,
indicating that the addition of three oxygen atoms took place at the aromatic structure and no
oxidation on the side chain. The second loss of water (fragment ion m/z 274) suggested that
the hydroxyl group on the aromatic structure was present next to a removable proton. The
second hydroxyl group can either occur in a carboxyl moiety or at other positions of the ring.
However, no carboxyl moiety was detected in negative ionization mode. The detection of TP
309 in the positive mode was likely ascribed to a hydroxylation of the ring. The appearance
of fragment ion m/z 114 demonstrated the ring-opening of the naphthalene group at 3,4-
position.
Cleavage. The fragment ions m/z 116 and 74 of TP 133 ([M + H]+ = 134.1176) were
formed by the loss of water and isopropyl group, indicating two hydroxyl groups of the
structure. The structure of TP 166 ([M - H]- = 165.0193) was proposed to form two carboxyl
moieties, which was supported by the fragment ion m/z 121 (165-121=44 Da, loss of CO2)
and 77 (121-77=44 Da, loss of CO2).
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3.4.2. Sulfate radical.
•-
Seven TPs detected in UV/PDS were ascribed to the oxidation by SO4 , where TP 133,
TP 166, TP 275-2, TP 307 and TP 309 were similar to those in UV/H2O2. TP 273 ([M + H]+
= 274.1437) corresponded to the addition of one oxygen atom to propranolol molecule with
one more double bond than TP 275. The fragment ion m/z 159 indicated the oxidation of
naphthalene group. A fragment ion m/z 131 was ascribed to a loss of CO of m/z 159. Hence,
the occurrence of double bond most likely took place on the side chain. An isomer of TP 291-
1 with different retention time and MS/MS spectra was denoted as TP 291-2. The difference
could be explained by the formation of two aldehyde moieties rather than double
hydroxylation on the ring, which was supported by the occurrence of m/z 131 and 103
through two sequential loss of CO (159-131=28 Da, and 131-103=28 Da).
3.4.3. Carbonate radical and chlorine radicals.
The addition of 50 and 500 mM bicarbonate in UV/H2O2 inhibited the formation of TP
291-1. Neither TP 275-1 nor TP 293 was observed in the presence of 500 mM bicarbonate,
•-
while TP 273 was generated. In such a condition, CO3 was the dominant radical. Thus the
•-
formation of TPs was attributed to the oxidation of propranolol by CO3 .
For UV/PDS, neither bicarbonate nor low concentration of Cl- affected the formation of
TPs. TP 275-1 appeared at high concentration of Cl-, which was due to the conversion of Cl•
•
•-
to OH (see discussion below). TPs generated by CO3 and Cl-containing radicals were
•-
similar to those by SO4 , indicating that the reaction pathways of propranolol degradation by
•-
•-
SO4 occurred for CO3 and Cl-containing radicals.
3.5. Proposed transformation pathway.
•
•OH pathway. OH attacks the naphthalene group of propranolol to form a carbon-
centered radical, which further reacts with oxygen to generate a peroxy radical and
subsequent forms a hydroxylated product (TP 291-1, Scheme 1). The oxidation of this
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product is followed by ring-opening and the formation of aldehyde moieties to produce TP
•
291-2. OH attacks the aldehyde moiety, leading to the formation of alcohol or/and carboxyl
group, namely TP 293 and TP 309. Additionally, the double bond is likely attacked by •OH in
the α-position of the aldehyde moiety by cleavage of acetaldehyde to form TP 281. Even
though several isomers of TP 281 were proposed, only one signal was detected. The cleavage
of ether bond on propranolol and its products generates TP 133 and TP166.
•-
SO4 pathway. The pKa of propranolol is 9.5, implying lower reactivity of protonated
•-
amine group at pH 8. Due to the electrophilic property of SO4 , it favors the oxidation of the
naphthalene group rather than the amine group, which leads to the formation of TP 275-2
rather than TP 275-1 (Scheme 1). The amine moiety could be considered as a secondary
reactive site when the oxidized naphthalene group is less reactive (i.e., TP 307). Hydroxyl as
an electron-donating group on naphthalene facilitates further oxidation on its ortho-position
•-
by SO4 , resulting in a ring-opening product (TP 291-2). Alternatively, the less selectivity of
•OH leads to the formation of multi-hydroxyl products (TP 291-1), which may occur on
different benzene rings. The formation of TP 273 is not clear, which may involve dehydration
of the side chain.
•-
•-
•-
CO3 and Cl-containing radicals pathway. CO3 and Cl2 are more selective oxidants
•
•-
compared with OH and SO4 ,(Buxton et al. 1988, Neta et al. 1988, Neta et al. 1977) thus
reacting with organic compounds mainly through electron transfer, which is similar to that of
•-
SO4 . Despite the fact that Cl• exhibits high reactivity toward organic compounds, which is
similar to •OH, Cl• could not be considered as a dominant radical in the system. Not only the
faster reverse rate of reaction 5 favors the formation of •OH at neutral pH, but also the excess
•-
Cl- consumes Cl• to form Cl2 .
•-
When CO3 is the dominant radical in both UV/H2O2 and UV/PDS, the same products
•-
•-
are formed as those by SO4 . With a low concentration of Cl- (0.1 mM), most SO4 reacts
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with propranolol, while only 4.5% of SO4 reacts with Cl- to generate Cl•. Therefore, no
effect was noticed on product formation compared with SO4 . As Cl- concentration increased,
•-
the formation of TP 275-1 was observed, which is likely ascribed to the oxidation by either
•OH or Cl•. Previous studies demonstrated that as Cl- concentration varied from 33 to 540
•
mM, the steady-date concentration of OH was three to five orders of magnitude higher than
that of Cl•.(Yang et al. 2014, 2016) Since the rate constant of OH with propranolol is near
•
•
the diffusion-controlled limit, OH is believed to the dominant oxidant contributing to the
degradation of propranolol rather than Cl•, leading to the formation of TP 275-1.
3.6. Oxidation in authentic water matrices.
The degradation of propranolol in groundwater was slightly slower than that in surface
water for both UV/H2O2 and UV/PDS. This opposite effect of bicarbonate in authentic vs.
simulated waters was likely ascribed to the scavenging effect of reactive components in
authentic waters (e.g., DOC). Kinetic modeling of steady-state concentration of radicals in
two authentic water matrices was shown in Table 2. A higher DOC concentration in
•-
groundwater decreased the concentration of radicals except for CO3 . Although the
concentration of CO3 was one or two orders of magnitude higher than that of •OH or SO4 in
•-
•-
•-
groundwater, the rate constant of CO3 with propranolol was three orders of magnitude lower
•
•-
•
•-
than that of OH or SO4 . Therefore, OH or SO4 was the dominant radical in both
groundwater and surface water, and their relatively low concentration in groundwater reduced
•-
the propranolol degradation rate. As the yield of SO4 (1.4) in UV/PDS was higher than that
of •OH (1.0) in UV/H2O2,(Baxendale and Wilson 1957, Mark et al. 1990) the degradation of
propranolol was faster in UV/PDS than that in UV/H2O2 in both water matrices.
Similar products were found in two water matrices (Fig. 4). TP 281 and TP 291-1 were
only observed in UV/H2O2, while TP 275-1 was not detected in any condition. A higher
2-
concentration of CO3 inhibited the formation of TP 291-1, confirming that hydroxylation
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was the dominant pathway of •OH. The maximum concentrations of TP 273 and TP 275-2 in
UV/PDS were higher than those in UV/H2O2, consisting with the results in the simulated
waters. The sharp decrease of these two products was observed by UV/PDS in surface water,
although the degradation rate of propranolol in two water matrices was similar. This result
•-
•-
indicates that SO4 was a stronger oxidant than CO3 to further oxidize these products.
Similar trends of products formation were also noticed for TP 291-2, TP 293, TP 307 and TP
309. The maximum concentrations of TP 293, TP 307 and TP 309 in UV/H2O2 were higher
than those in UV/PDS, while the faster degradations of products were found in surface water
•
rather than those in groundwater, owing to the further oxidation of products by OH. The
higher concentration of the cleavage product TP 133 by UV/H2O2 was due to the different
•-
reactivity of •OH and SO4 toward the side chain. In groundwater, both TP 166 and TP 291-2
exhibited higher concentration than those in surface water, which was likely attributed to
•-
either the lower reactivity of CO3 toward these products, or the oxidation of their precursors
•
•-
by OH and SO4 . These comparisons between two matrices simulated the formation of
products in real-world applications of these two AOPs.
3.7. Acute toxicity of transformation products in UV-based AOPs.
Microtox assay has been widely employed to determine the acute toxicity of substances
in the environment. A model marine bacterium of Vibrio fischeri was selected herein as an
indicator of toxicity, because it is tolerant to the high concentration of salts used in this study
(100 mM bicarbonate or Cl-). The acute toxicity was expressed by the luminescence
inhibition of Vibrio fischeri in the treatment of propranolol via different procedures (Fig. 5).
L0 was the luminescence of propranolol without treatment, while
L was the luminescence of
samples with corresponding treatments and conditions. The acute toxicity was determined by
the ratio of L/L0, where a lower value implies higher acute toxicity, and vice versa. The
dashed line represented the luminescence of residual propranolol in a sample.
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With the decrease of propranolol in UV/H2O2, the inhibition effects on Vibrio fischeri
decreased up to 20% relative to the initial luminescence. This result was consistent with the
toxicity of residual propranolol, which can be explained by the fewer toxic products
•
generated by OH. In UV/PDS, 20% degradation of propranolol led to ~80% inhibition of
luminescence. When propranolol was removed by 40%, the luminescence was completely
•-
inhibited, suggesting that the products generated by SO4 were more toxic than propranolol.
•-
The effects of oxidation products of CO3 or Cl-containing radicals were also shown in
Fig. 5. The concentration of bicarbonate or Cl- at 100 mM was used to create a background
•-
with dominant CO3 or Cl-containing radicals. The presence of bicarbonate in UV/ H2O2
showed no luminescence inhibition when the removal of propranolol was less than 30%.
However, the toxicity sharply increased as the degradation of propranolol proceeded.
•
•
Bicarbonate at 100 mM could scavenge 77% of OH, implying that OH contributed to the
partial degradation of propranolol and the formation of its corresponding products. The non-
effect on Vibrio fischeri in the initial phase could be explained by two possible reasons: either
•OH generated fewer toxic products, or the accumulation of toxic products by CO3 was not
•-
sufficient to affect the overall toxicity. Subsequently, the further oxidation of products by
•-
•OH or CO3 generated more toxic products. The presence of bicarbonate or Cl-containing
radicals in UV/PDS exhibited comparable toxicity to that in UV/PDS. Taken together, these
•-
•-
results indicated that the products generated by SO4 , CO3 or Cl-containing radicals were
more toxic than those by •OH.
439 4. Conclusions.
440
441
442
Hydroxyl radical showed unselective oxidation towards propranolol species. Although
•-
SO4 was expected to be more reactive toward the neutral form of propranolol, the
•-
electrostatic attraction between SO4 and the protonated form of propranolol could facilitate
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this reaction. OH reacted with either amine moiety or naphthalene group through
hydroxylation pathway, which underwent further oxidation to form ring-opening products.
•-
SO4 exhibited high reactivity toward the electron-rich naphthalene group. When the
oxidized naphthalene group was less reactive, the amine moiety as a secondary reactive site
•-
could be oxidized by SO4 . The same products through the cleavage of the side chain were
observed in both AOPs. Neither bicarbonate nor Cl- had a significant effect on propranolol
•-
degradation. CO3 and Cl-containing radicals were favorable in oxidizing the naphthalene
•-
•-
•
group. Since Cl2 played a role in the conversion of SO4 to OH, the characteristic product
by OH was detected at high concentrations of Cl- in UV/PDS. The acute toxicity assay
•
•-
•
•-
implied that the products generated by SO4 were more toxic than those by OH. CO3 and
•-
Cl-containing radicals gave similar toxic products as SO4 . The presence of bicarbonate in
UV/H2O2 enhanced the generation of toxic products. It should be noted that the toxicity of
specific product needs to be further identified, which will facilitate a better understanding of
toxicological potential when these AOPs are applied in treating waters with different
backgrounds.
458
459 Appendix A. Supplementary data
460
461
Supplementary data related to this article can be found at:
462 Acknowledgments
463
464
465
466
We acknowledge the Chinese International Postdoctoral Exchange Fellowship Program
(No. 20160074) for support for Y.Y. We are thankful for the Excellent Graduate Student
Scholarship from the Shanghai Tongji Gao Tingyao Environmental Science and Technology
Development Foundation awarded to X. Lu.
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467 Figures and tables.
468
469
470
471
472
Fig. 1. Apparent second-order rate constants for the reactions of propranolol with (A) •OH
•-
and (B) SO4 .
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UV/H2O2 (control)
1.0
0.8
0.6
0.4
0.2
0.0
UV/H2O2 + 5 mM NaHCO3
UV/H2O2 + 50 mM NaHCO3
UV/H2O2 + 500 mM NaHCO3
UV/PDS (control)
UV/PDS + 5 mM NaHCO3
UV/PDS + 50 mM NaHCO3
UV/PDS + 500 mM NaHCO3
0
5
10
15
20
25
30
35
Time (min)
473
474
Fig. 2. Effect of bicarbonate on degradation of propranolol in UV/H2O2 or UV/PDS at pH 8.
475
476
477
Experimental condition: [propranolol]0 = 20 µM, and [H2O2]0 or [PDS]0 =1 mM.
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UV/PDS (control)
1.0
0.8
0.6
0.4
0.2
0.0
UV/PDS + 0.1 mM NaCl
UV/PDS + 1 mM NaCl
UV/PDS + 10 mM NaCl
UV/PDS + 100 mM NaCl
0
5
10
15
20
Time (min)
478
479
Fig. 3. Effect of chloride on degradation of propranolol in UV/PDS at pH 8. Experimental
480
481
condition: [propranolol]0 = 20 µM, and [PDS]0 =1 mM.
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482
Table 1. Products detected by TOF-MS in UV/H2O2 and UV/PDS.
Product ID
Propranolol
RT
ESI
Observed
Calculated
Mass
Molecular
formula
Proposed structure
(min) (+/-) Mass
13.8
+
260.16491
260.16451
C16H21NO2
TP 133
TP 166
1.1
0.9
+
-
134.11756
165.01933
134.11761
165.01934
C14H19NO5
C8H6O4
N
H
OH
OH
TP 273
11.0
+
274.14377
274.144
C16H19NO3
TP 275-1
TP 275-2
2.5
9.6
+
+
276.15942
276.15942
276.16687
276.16687
C16H21NO3
C16H21NO3
TP 281
1.1
1.7
+
+
282.1336
282.13387
292.15295
C14H19NO5
C16H21NO4
TP 291-1
292.15433
TP 291-2
TP 293
10.3
2.5
+
+
292.15433
294.16998
292.15295
294.17032
C16H21NO4
C16H23NO4
TP 307
TP 309
1.7
3.1
4.0
1.6
2.9
+
+
308.14925
310.1649
308.14981
310.16515
C16H21NO5
C16H23NO5
OH
O
OH
H
N
O
OH
483
484
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486
•
•-
•-
Scheme 1. Proposed degradation pathways for propranolol by OH, SO4 , CO3 and Cl-
•
487
488
489
490
491
containing radicals. Red boxes indicated the generation of products by OH; green boxes
•-
•-
indicated the generation of products by SO4 , CO3 and Cl-containing radicals; blue boxes
indicated the generation of products in all processes.
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492
Table 2. Modeled molar concentrations of inorganic radicals for various water matrices a
UV/H2O2
UV/PDS
Reactive
species (M)
Groundwater Surface water
Groundwater Surface water
•-
[SO4 ]
2.20E-13
4.19E-14
7.80E-16
1.80E-15
4.51E-12
4.03E-13
1.57E-13
1.21E-15
1.03E-14
4.72E-13
[•OH]
[Cl•]
6.67E-14
2.62E-22
6.31E-22
1.95E-12
1.35E-13
4.42E-22
3.86E-21
1.50E-13
•-
[Cl2 ]
•-
[CO3 ]
493
494
a. Simulation without propranolol. Simulation time = 5 min, 1 mM H2O2 or 1 mM PDS.
495
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497
Fig. 4. Propranolol degradation and main transformation products (TPs) formation in
authentic waters. GW and SW represent the groundwater and the surface water, respectively.
Peak areas were normalized to the peak area of the internal standard. Experimental condition:
498
499
500
501
502
[propranolol]0 = 1
µM, [H2O2]0 or [PDS]0 = 1 mM.
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503
504
Fig. 5. Impact on Vibrio fischeri luminescence by propranolol after different treatments
505
506
507
508
509
with/without bicarbonate or chloride. The dash line represents the luminescence induced by
the remaining propranolol. Errors represent the standard deviation (n = 4). Experimental
-
condition: [propranolol]0 = 20
µ
M, [HCO3 ] or [Cl-] = 100 mM, [H2O2]0 or [PDS]0 =1 mM.
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510 References
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