Science of the Total Environment 734 (2020) 139446

Contents lists available at ScienceDirect

Science of the Total Environment

journal homepage: www.elsevier.com/locate/scitotenv

Degradation of sulfonamide antibiotics using ozone-based advanced

oxidation process: Experimental, modeling, transformation mechanism
and DFT study
Rasool Pelalak a,b, Reza Alizadeh a,b,⁎, Eslam Ghareshabani c, Zahra Heidari a,b
a
Chemical Engineering Faculty, Sahand University of Technology, P.O. Box 51335-1996, Sahand New Town, Tabriz, Iran
b
Environmental Engineering Research Center (EERC), Sahand University of Technology, P.O. Box 51335-1996, Sahand New Town, Tabriz, Iran
c
Physics Faculty, Sahand University of Technology, P.O. Box 51335-1996, Sahand New Town, Tabriz, Iran

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Degradation of SSZ, SMX, SMZ and MTZ

molecules was investigated under O3,
H2O2 and O3/H2O2 processes.
• The kinetic experimental study and syn-
ergistic effect of O3/H2O2 reaction were
evaluated.
• ANN and CCD based-RSM modeling
were developed to predict degradation
efficiency (%) of SNAs and results were
compared.
• Second order quadratic modeling was
successfully developed to determine
the optimum conditions.
• The LC–MS/MS analysis and DFT calcu-
lations were carried out to identify the
main degradation intermediate
molecules.

a r t i c l e i n f o a b s t r a c t

Article history: In this research, degradation of three sulfonamide antibiotic compounds (SNAs) such as Sulfasalazine (SSZ), Sulfa-
Received 29 March 2020 methoxazole (SMX) and Sulfamethazine (SMT) as well as Metronidazole (MNZ) were investigated for the first
Received in revised form 12 May 2020 time using experimental, modeling and simulation data under O3, H2O2, and O3/H2O2 systems. The kinetic and syn-
Accepted 12 May 2020
ergistic study confirmed the pseudo-first-order reaction and highest performance of the O3/H2O2 process for the
Available online 15 May 2020
SNAs degradation process. Two modeling approach, central composite design (CCD) based on response surface meth-
Editor: Frederic Coulon odology (RSM) and artificial neural network (ANN) were utilized to investigate the optimization and modeling of SSZ
degradation as the response of O3/H2O2 system and results were compared. The individual and interactive effects of
Keywords: main operational parameters were also possessed by the main effect graphs, contour and response surface plots. The
Sulfonamides antibiotics experimental results showed maximum degradation efficiency at the optimum condition for SSZ, SMX, SMT and MNZ
Ozone-based advanced oxidation process were 98.10%, 89.34%, 86.29% and 58.70%, respectively in O3/H2O2 process. For proposed reaction mechanism of SNAs
Response surface methodology in O3/H2O2 process the influence of inorganic salts including Na2SO4, NaH2PO4, Na2CO3, NaCl and tert butanol (TBA) as
Artificial neural network organic •OH scavenger was studied. Besides that, LC-MS/MS analysis and DFT calculation were employed to identify
Intermediate molecules
the intermediate molecules produced (31 species) during the SSZ degradation (as a SNAs model) and a probable deg-
DFT calculation and degradation pathways
radation pathway was proposed. The results provided a new strategy by combination of experiment and computer
simulation to evaluate the O3/H2O2 system for optimization of SNAs removal from wastewater.
© 2020 Elsevier B.V. All rights reserved.

⁎ Corresponding author at: Chemical Engineering Faculty, Sahand University of Technology, P.O. Box 51335-1996, Sahand New Town, Tabriz, Iran.
E-mail address: r.alizadeh@sut.ac.ir (R. Alizadeh).

https://doi.org/10.1016/j.scitotenv.2020.139446
0048-9697/© 2020 Elsevier B.V. All rights reserved.
2 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446
1. Introduction
In the last decade, pharmaceutical and personal care products
(PPCPs) can be catalogued as emerging priority pollutants in wastewa-
ters. There is soaring worry about the widespread presence of PPCPs and
their metabolites in water streams which is increased with rapid growth
of the population and urbanization. Many of these toxic contaminants
persist in the environment and cause adverse effects on ecosystems
(Liancai et al., 2018). Lately, Advanced Oxidation Processes (AOPs)
have appealed many attentions as an effective technology for degrada-
tion of organic contaminants from wastewater (Gil et al., 2018;
Agbaba et al., 2010; Zhou et al., 2020). In water treatment applications,
usually AOPs refer to a specific subset of processes that involve O3 mol-
ecule, Fenton and/or UV light (Andreozzi et al., 1999; Gurol and Vatistas,
1987; Pelalak et al., 2020; Heidari et al., 2020) which can decrease the
concentration of pollutants from several hundred ppm to b5 ppb, in
proper condition (Munter, 2001). Due to feasibility, accessibility and
high reactivity of ozone, ozonation have been a selected as a common
degradation process in the wastewater treatments (Yuan et al., 2013).
However, solubility limitation, stability in water and also the selective
reactivity of ozone are the drawbacks of this technology. Modification
of the ozonation process, which is called the ozone-based advanced ox-
idation processes, was proposed as a solution to overcome these draw-
backs. In these processes decomposition of ozone in aqueous solution
produce many powerful reactive oxidative species (ROSs) such as hy-
droxyl radicals (•OH), •O, HO2•, HO4• and O2•. Among these ROSs, the
•OH due to its powerful (oxidation–reduction potential = 2.80 eV)
and non-selective oxidation structure can reacts very fast with most or-
ganic pollutants in solution (Oturan and Aaron, 2014). O3/H2O2 process
as an ozone-based process, can generate strong oxidants like •OH, ac-
cording Eq. (1). In this process H2O2 catalyze O3 decomposition and re-
sult in formation of more •OH.
H2 O2 þ 2O3 →2HO˙ þ 3O2
O3/H2O2 systems have been applied in the degradation of water con-
taminant and demonstrated its capability in such process (Alizadeh
Kordkandi and Mohaghegh Motlagh, 2018; Cruz-Alcalde et al., 2020).
Additionally, the O3/H2O2 process has received more attention than
ozonation reaction because it can quickly decrease the generation of
key intermediates of bromate (HOBr/OBr) back to bromide and conse-
quently minimize the bromate procreation. Also, the efficiency and re-
action rate in the O3/H2O2 is higher than those of each processes when
used separately (Mansouri et al., 2019). However, one of the crucial
points in this kind of AOP is the ratio of ozone to hydrogen peroxide,
which should be in optimal level in order to reach a high efficiency of
contaminants abatement. Otherwise, with increasing and decreasing
the concentration of hydrogen peroxide in the medium, it acts as a rad-
ical scavenger according to Eqs. (2) and (3) (Elmolla et al., 2010;
Moussavi et al., 2009):
H2 O2 þ ˙OH→H2 O þ HO˙2 ; k ¼ 2:7  107 M−1 s−1
HO2 ˙ þ ˙OH→H2 O þ O2 ; k ¼ 7:1  109 M−1 s−1
As two main oxidants are involved in O3/H2O2 reaction, the investi-
gation of the process is a little bit complex (Russell, 2006). The conven-
tional method for investigation the effect of different factors (one factor
at a time) is very time consuming and also expensive. Moreover, in the
conventional method a large number of experiments should be re-
peated while it could not determine the interactions between different
parameters. To overcome these problems and get more insight into the
process, a process modeling could be of great helpful. By employing cen-
tral composite design (CCD) based on response surface methodology
(RSM) the impact of several factors and interactions can be evaluate
by the minimum number of experiments which consequently provide
an optimized design of process. Another modeling and optimization
technique which is very common in this context is artificial neural net-
work (ANN). In ANN modeling the mathematical description of the pro-
cess is not required and modeling is based on training and prediction of
data while RSM mainly uses statistical analysis for optimizing the pro-
cess. Moreover, ANN method is much faster than RSM for the prediction
of response of the system. Therefore, ANN is recognized as a proper ap-
proach for modeling and simulation of different AOPs. In the recent
years, the presence of sulfonamide antibiotics (SNAs) as hazardous or-
ganic contaminants in surface water and sewage treatment plant efflu-
ents have been reported in the range of ng/L to μg/L (Ingerslev and
Halling-Sørensen, 2000; Rabølle and HenrikSpliid, 2000; Lei et al.,
2019; Li et al., 2019) which indicated that these components cannot
be eliminated completely during the conventional treatment. The SNA
residues were reported in different animal tissues such as muscle,
liver, kidney, skin, fat and in the food chain such as tissue, milk, meat,
eggs and fish (Qiao et al., 2018; Baran et al., 2011; Qin et al., 2019; Yu
et al., 2018). Hence, it is very important to develop a treatment technol-
ogy to remove SNAs and their metabolites from aqueous and prevent
their harmful impacts to the environment. Therefore, the study of
SNAs degradation by ozone-based advanced oxidation process was se-
lected as one of the scope of this work.
Herein, the degradation of three sulfonamide antibiotic compounds
that consist of sulfonamide functional group named SSZ, SMX and SMT
as well as MNZ as an inflammatory bowel disease drug were investi-
gated firstly in aqueous media by O3/H2O2 process. The synergistic effect
of O3/H2O2 system was followed by wastewater treatment performance
tests. Also, a comparative study was performed to evaluate the perfor-
mance of RSM and ANN as two efficient modeling techniques in the pre-
diction of sulfonamides elimination from aqueous medium by O3/H2O2
process. To the best of our knowledge, the modeling of sulfonamides
degradation namely SSZ in aqueous media by O3/H2O2 process has not
been reported so far. The effect of different operational parameters
ð1Þ such as ozone concentration (mg/L), initial H2O2 concentration (Mm),
initial SSZ concentration (mg/L) and Reaction time (min) to find the
treatment condition with proper performance were also investigated
by the main effect graphs, contour and response surface plots. As the re-
sult, the findings attained via CCD were appropriately compared with
ANN modeling predictions. Moreover, in order to reach the maximum
degradation efficiency, the optimized point of operational conditions
were obtained and was compared with RSM and ANN predicted data.
LC-(+ESI)-MS/MS analysis employed to identify the intermediates pro-
duced during the contaminants degradation and reasonable degrada-
tion pathway was proposed. Only few researches have been reported
to intermediated product of SNAs especially SSZ degradation in AOPs.
In the present work for the first time, the most susceptible site of SSZ,
SMX, SMZ and MNZ molecules which could be attacked by •OH/O3 oxi-
dative species, were also investigated by DFT calculations. Additionally,
in order to evaluate the application of O3/H2O2 process in real wastewa-
ter treatment the effect of common inorganic salts including Na2SO4,
NaH2PO4, Na2CO3, NaCl and tert butanol (TBA) as organic •OH scavenger
ð2Þ was studied on the degradation of SNAs pollutants.
ð3Þ 2. Experimental procedure
2.1. Chemicals and reagent
The chemicals and reagents, which were used as received, are listed
in Text S1.
2.2. Experimental set up and procedures
The experiments were performed using an ozone generator (LAB
802, Ozomatic, Germany) which was capable of producing up to 4 g
ozone per hour. The ozonation of surrogate wastewater was carried
out in a semi-batch bubble column with the diameter and height of 5
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446
and 30 cm, respectively. As shown in Fig. 1 the ozone generator appara-
tus has been fed with pure oxygen which was stored in the cylinder.
Since only a portion of the input oxygen was converted to ozone, an
ozone gas analyzer monitors the amount of the generated ozone mole-
cule (1 to 9 mg/L) at the output line of the apparatus. Also, the inlet flow
rate of ozone gas (1 L/h) was measured using a flow meter before the
bubble column reactor. The outlet gas from this reactor returns to the
ozone catalytic destructor for neutralizing the ozone gas. In each run,
250 mL of the reaction solution including certain concentrations of
pharmaceutical (5 to 25 m/L) was supplied. During 40 min of experi-
mental run 4 mL of the sample was withdrawn from the column at 8 dif-
ferent ozonation times to track the degradation efficiency (%
D) according the Eq. (4).


½C
Degradation efficiency of antibiotic ð%DÞ ¼ 1−  100
½C 0
where [C]0 and [C] are the antibiotic concentration (mg/L) at the initial
and the end of the reaction, respectively. In order to prevent from fur-
ther oxidation of the ozone molecules or •OH, 1 mL of 0.01 M Na2SO4
were added to the samples. The removal of pharmaceuticals was
tracked using UV–Vis spectrophotometer (UV-2100 Unico, USA) in the
maximum wavelength peaks of the contaminant (λmax) (Pelalak et al.,
2013). It is worth to mention that prior to the beginning of the experi-
ments the degradation of sulfonamides had been evaluated by HPLC
analysis, and results were close to the UV results. In order to study the
reaction mechanism in O3/H2O2 process, the effect of various inorganic
ions and •OH scavengers such as Na2SO4, NaH2PO4, Na2CO3, NaCl and
tert-butanol (TBA) on the degradation of SSZ was studied. Also, In
order to proposed of degradation pathways of SNAs and for identifying
and quantifying different intermediates products in O3/H2O2 process
liquid chromatography–mass spectrometry (LC-MS/MS) technology
was used.
2.3. LC-MS/MS analysis
For Liquid chromatography–mass spectrometry, acetonitrile from
Duksan Pure Chemicals (LC-MS grade, South Korea) was used to pre-
pare the mobile phase. LC-MS analyses were carried out on 3200
QTrap mass spectrometer (AB SCIEX, Framingham, MA, USA) with an
Fig. 1. Schematic illustration of the experimental setup.
3
enhanced mass spectrum (EMS) scan in positive mode and under con-
dition of: Scanning region: 50–1000 m/z, sampling period: 0.1 s, tem-
perature of heating module and CDL:450 °C, 350 °C, respectively. The
column was a Kinetex 2.7 m, C18 100 Å, 100 mm × 2.1 mm.
2.4. Computational method
Density functional theory (DFT) calculations were performed
with Gaussian 16 software (Frisch et al., 2016), using the M06-2X
functional (Zhao and Truhlar, 2008) and 6-31+G(d) basis set. In
−
this study, the P + k and P k Parr functions (Domingo et al., 2013)
were introduced to characterize the nucleophilic and electrophilic
attack of antibiotic molecules. The electrophilic, P + k , and nucleo-
philic, P−
k , Parr functions, were obtained through the analysis of the
Mulliken atomic spin density of the radical anion and the radical cat-
ð4Þ
ion by single-point energy calculations over the optimized neutral
geometries using the unrestricted DFT formalism for radical species.
The open-shell reaction mechanism studied by unrestricted B3lYP
functional (Ozen and Aviyente, 2003) and 6-31+G(d) basis sets.
We used QST2 method (Peng and Schlegel, 1993) for finding the
transition state structures. Transition state structures have been con-
firmed by frequency analyses at the same level.
2.5. Modeling approaches
2.5.1. Response surface methodology common
The second-order model is the most regularly used method for ap-
proaching the polynomial models in RSM. One of the most regular de-
signs for this model is central composite design (CCD). The
experimental values were examined employing the Minitab 17 soft-
ware. The number of experiment runs (N) for this strategy is defined
as N = 2k + 2 k + Cp, where k is the number of variables and Cp is
the number of central points. In this regard, four main parameters
with 5 levels were chosen: initial SSZ concentration (mg/L), influent
ozone concentration (mg/L), initial hydrogen peroxide concentration
(mg/L) and reaction time (min). In accordance with the prior relation,
the CCD is consisted of a 24 full factorial design, 8 axial points and 7 rep-
lications at the center point. Overall, the experimental design comprised
of 31 runs which were done in a random order to minimize the influ-
ences of variability in the observed responses due to extraneous factors.
4 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

Table 1 number of layers, the number of nodes in each layer, and the nature of
The ranges and levels of the independent variables used in experimental runs. the transfer functions. Finding the optimum ANN topology is challeng-
Symbol Ranges and levels ing since there is no direct procedure for this, and usually a trial and
Variables error method is utilized for constructing a proper model. Due to validate
(Xi) −2 −1 0 +1 +2
the ANN model, K-fold methodology was employed to discover the op-
Ozone concentration (mg/L) (X1) 1 3 5 7 9
timal set of data. Input variables to the ANN were the same as RSM input
Initial H2O2 concentration (X2) 0.02 0.06 0.1 0.14 0.18
(mM) variables. The limit of variables studied is defined in Table 2. 31 experi-
Initial SSZ concentration (mg/L) (X3) 5 10 15 20 25 mental sets were used to the built ANN model and arranged into train-
Reaction time (min) (X4) 10 17.5 25 32.5 40 ing and validation subsets which consist of 20 and 11 samples,
respectively. The statistical analysis software of JMP Pro 14 was utilized
to organize the ANN modeling and the results analysis. The software can
For simplification of the statistical estimations, the parameters Xi were consider categorical factors as input for ANN fitting. The optimal design
coded as xi according to the Eq. (5). of the ANN model and its parameter variation were specified based on
the minimum value of the root-mean-squared error (RMSE) of the
Xi −X0 training and validation data groups (Shirazian et al., 2019; Zarei et al.,
xi ¼ ð5Þ
δX 2010).

where X0 is the real value of Xi at the center point and δX presents the
step change between them (Myers et al., 2011). The ranges of experi- 3. Results and discussion
mental and the coded levels of the independent variables for SSZ degra-
dation which were selected based on some preliminary experiments are 3.1. Performance of O3/H2O2 process for destruction of SNAs and kinetics
shown in Table 1. The value of α, depends on the number of points in study
the factorial portion of the design, as shown in Eq. (6), which here α is
equal to 2. The effect of various treatment processes on the removal of SNAs
and MNZ were carried out under the experimental conditions of
1 5 mg/L ozone concentration, 0.1 mM H2O2 concentration and 10 mg/L
1 initial SSZ concentration, which results are presented in Fig. 2. Accord-
¼ ð2kÞ4
α ¼ ðN F Þ4 ð6Þ ing to Fig. 2 (a), it is obvious that the degradation efficiency of SSZ,
SMX, SMZ and MNZ by O3/H2O2 process were obtained around
79.60%, 71.68%, 67.08% and 38.01% respectively, while the degradation
2.5.2. Artificial neural network in the same operating conditions by ozonation alone were achieved
The most principal step in the development of an ANN model is the 61.44%, 53.93%, 51.09% and 26.90%, respectively. It is clear that the O3/
optimization of its topology. The topology of an ANN is described by the H2O2 treatment process showed an effective potential in the

Table 2
The 4-factor central composite design matrix and the value of response function (%).

Uncoded values Removal efficiency of SSZ (% D)

Run Predicted
Type of data [O3]0 (mg/L) [H2O2]0 (mM) [SSZ]0 (mg/L) Reaction time (min) Experimental
CCD ANN

1 Training 7 0.14 20 17.5 48.00 48.89 45.45

2 Training 3 0.06 20 32.5 31.90 31.99 32.39
3 Validation 7 0.06 10 17.5 57.60 57.55 60.90
4 Training 3 0.06 20 17.5 13.00 13.39 14.67
5 Validation 3 0.06 10 32.5 61.49 61.10 58.68
6 Validation 3 0.14 20 32.5 43.00 43.56 45.22
7 Validation 7 0.06 20 32.5 56.01 57.95 56.40
8 Training 7 0.06 20 17.5 38.05 38.98 40.51
9 Validation 5 0.10 15 25.0 53.39 53.33 53.40
10 Training 3 0.14 20 17.5 22.40 22.63 20.53
11 Training 5 0.10 15 40.0 71.15 70.72 72.80
12 Training 5 0.10 15 25.0 50.42 53.33 53.40
13 Training 5 0.10 15 25.0 53.41 53.33 53.40
14 Training 5 0.10 15 25.0 54.30 53.33 53.40
15 Training 7 0.14 20 32.5 69.70 70.19 67.37
16 Training 5 0.10 15 25.0 54.30 53.33 53.40
17 Training 5 0.02 15 25.0 42.68 41.93 41.69
18 Validation 5 0.10 15 10.0 29.54 29.71 29.97
19 Training 7 0.14 10 17.5 55.99 55.65 58.77
20 Training 5 0.18 15 25.0 51.12 51.60 52.81
21 Training 5 0.10 15 25.0 53.23 53.33 53.40
22 Validation 5 0.10 25 25.0 37.03 34.32 30.77
23 Training 9 0.10 15 25.0 73.46 71.81 73.10
24 Training 3 0.14 10 32.5 62.10 60.87 61.36
25 Validation 5 0.10 5 25.0 67.80 70.20 67.03
26 Validation 5 0.10 15 25.0 54.30 53.33 53.40
27 Training 1 0.10 15 25.0 27.64 29.03 29.17
28 Training 7 0.14 10 32.5 77.90 78.05 77.46
29 Validation 7 0.06 10 32.5 78.10 77.62 77.68
30 Validation 3 0.14 10 17.5 40.26 38.82 39.15
31 Training 3 0.06 10 17.5 42.14 41.39 38.75
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446 5

80
80 Sulfasalazine (a) 70
Sulfasalazine (b)
70 Sulfamethoxazole Sulfamethoxazole
Sulfamethazine

Degradation (%)
60 Sulfamethazine

Degradation (%)
60 Metronidazol Metronidazol
50
50
40
40

30 30

20 20

10 10

0 0
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Time (min) Time (min)

80 1.8
Sulfasalazine Sulfasalazine, y = 0.042x, R² = 0.98
Sulfamethoxazole 1.6 Sulfamethoxazole, y = 0.035x, R² = 0.97
70
Degradation (%)

Sulfamethazine 1.4 Sulfamethazine, y = 0.029x, R² = 0.97

60

Ln ( C0 / Ct )
Metronidazol
1.2 Metronidazol, y = 0.013x, R² = 0.96
50
1
40
0.8
30 0.6
20 0.4
10 0.2
(c) (d)
0 0
0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
Time (min) Time (min)

Fig. 2. Comparison of various processes for removal of different antibiotic; (a) O3 process, (b) H2O2 process, (c) O3/H2O2 process (d) plots of ln(C0/Ct) versus reaction time (min);
Experimental conditions: [C]0 = 10 mg/L, [O3]0 = 5 mg/L, [H2O2]0 = 0.1 mM and ozone gas flow rate = 1 L/h.

degradation of SNAs. SNAs can be efficiently oxidized by direct attack of The changes in absorption spectra of SNAs and MNZ during O3/H2O2
the ozone molecule or •OH generated in the bulk solution according re- process are shown in Fig. 1S. The absorption peak of SSZ, SMX, SMT and
action (1). As expected from Eq. (1), H2O2 catalyzes O3 decomposition MNZ are located at 363, 266, 261 and 319 nm respectively. The decrease
leading to formation of more •OH and eventually the more degradation in the absorption intensity peak for all contaminants in 40 min was ob-
of the contaminants. Synergistic effect has been vastly reported in the viously observed which indicates the SNAs and MNZ degradation dur-
literature as a parameter to estimate the performance of co-operation ing O3/H2O2 process.
in multifactor processes. Therefore, to have a correct interpretation of
the important role of H2O2 in O3/H2O2 process, the synergy factor was 3.2. CCD methodology and model consequence for O3/H2O2 process
evaluated as follows:
The CCD results were subsequently used for optimizing the system
kapp;Anti ozone=H2 O2 factors by Response Surface Methodology (RSM). The 31 designed runs
synergy factor ¼ ozonation þ kapp;Anti H2 O2
kapp;Anti were based on 5 levels and 4 main factors, including 7 replications at cen-
ter point. The model values were predicted by CCD technique and the em-
According what is reported in the Table 2S, synergy factor is higher pirical data of sulfasalazine degradation efficiency are listed in Table 2.
than one for binary processes and the highest factor has been reported The quadratic polynomial response equation was used to calculate
for the case of sulfasalazine degradation with O3/H2O2 process (1.72). the predicted response of process. This equation which contained the
In order to calculate kinetic model of SNAs degradation by the O3/H2O2 interaction terms, is according to the Eq. (9):
process, Eq. (7) was presumed:
X
k X
k k−1 X
X k
d½SNAs  Y ¼ β0 þ βi xi þ βii x2i þ βij xi x j þ ε i≠j ð9Þ
r¼− ¼ kapp ½SNAs  ð7Þ
dt i¼1 i¼1 i¼1 j¼2

where kobs represents the reaction rate constant and [SNAs] is the con- where Y is the response, β0 is the constant, βi is linear effect of the factor
centration of sulfonamides antibiotics (mg/L). The reaction rate con- xi, βii is the quadratic effect of the factor xi, βij is the interaction effect be-
stant could be obtained by calculation through slope of plot of ln(C0/ tween the input factors, ε and k are the residual term and number of fac-
C) against reaction time according to Eq. (8) (Pelalak and Heidari, tors studied for optimization of experiments, respectively. Based on the
2014): empirical outputs an experimental formula (Eq. (10)) which was a qua-
dratic polynomial equation between variables and response, was appro-
C0
ln ¼ kapp t ð8Þ priately suggested for the system modeling.
C

where C0 and C are the concentration of antibiotics at time t = 0 and t Y ¼ 53:339 þ 10:695x1 þ 2:418x2 −8:968x3 þ 10:252 x4
respectively. Fig. 2(d) illustrated a liner fit of the O3/H2O2 degradation þ 0:167x1 x2 þ 2:360x1 x3 þ 0:091x1 x4 þ 2:953x2 x3
time against ln(C0/C). Therefore, degradation decay of the pharmaceuti- þ 0:583x2 x4 −0:277x3 x4 −0:7298x21 −1:642x22 −0:268x23 −0:781x24
cals by O3/H2O2 process was observed to conform a pseudo first order
ð10Þ
kinetic model (Table 2S).
6 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

Table 3 from the straight baselines demonstrate the effectiveness of the

Analysis of variance for fit of removal efficiency from central composite design. model. These explanations confirm that the mathematical model is sat-
Removal of sulfasalazine isfactorily fitted.
Source of variations In order to evaluate the significance of different coefficients in the
DF Mean square F-value P-value
model, not only the t-value and P-value are employed but also the Pa-
Regression 14 547.78 214.68 0.000
reto analysis is a suitable method for this purpose (Hosseini et al.,
Linear 4 1834.54 718.98 0.000
Square 4 23.73 9.3 0.000 2019; Samarb et al., 2019). The significance of each term of model in-
Interaction 6 39.32 15.41 0.000 cluding the main factors plus their interactions is estimated by the fol-
Residuals Error 16 2.55 – – lowing relationship (Eq. (11)) (Khataee et al., 2010):
Lack-of-Fit 10 2.96 1.57 0.299
Pure Error 6 1.88 – –
!
β2i
R2 = 0.994, R2(Adj) = 0.980. Pi ¼ P 2  100 i≠0 ð11Þ
βi

3.2.1. Analysis of variance (ANOVA) where βi is the coefficient value of ith factor which is reported in
The model predicted values for SSZ degradation efficiency were Table 3S. The results of Pareto analysis is illustrated by Fig. 3 which is
attained by means of the quadratic polynomial model of Eq. (10) and consisted of the distinct main variables and their interactions. As it is ev-
represented in Table 3. As evidenced by Table 3, an acceptable agree- ident by Fig. 3, all of the four main factors demonstrated a remarkable
ment was considered between the model predicted and the experimen- effect on the removal of SSZ contaminate. The contributions of different
tal data. This issue was well approved by the high correlation coefficient terms in degradation yield of SSZ are in the order of: ozone concentra-
of the model (R2 = 0.994). This means the CCD model can be used at tion (β1) reaction time (β4), initial drug (SSZ) concentration (β3) and
about 99% variability in the system response which is originated via the interaction term of initial ozone concentration and inlet SSZ concen-
the independent parameters and also their interactions (Sahoo and tration (β13) with importance values of 35.26%, 32.43%, 24.77% and
Gupta, 2012; Lambropoulou et al., 2017). Table 3 included the results 2.69%, respectively.
of the analysis of variance (ANOVA) which showed the significance Due to achieve the simple and best fitted model for the degradation
and suitability of the achieved CCD model. The fitting quality for second yield of sulfasalazine the unimportant coefficients can be ignored from
order model was determined by correlation coefficient (R2), and its sta- the CCD model. The simplified quadratic response surface model is
tistical importance was checked by the F-test (Fischer variation ratio). outlined in coded form as Eq. (12).
According to Table 3, both of the linear and square terms of the model
have very remarkable influences on yield of sulfasalazine decay (P- Y ¼ 53:339 þ 10:695x1 þ 2:418x2 −8:968x3 þ 10:252 x4
value b 0.05). Moreover, the interactions between the independent pa- þ 2:360x1 x3
rameters of the model are the important terms which have considerable þ 2:953x2 x3 −0:7298x21 −1:642x22 −0:268x23 −0:781x24 ð12Þ
influences on the system response. As it is evident by ANOVA table, the
calculated F-value which is about 214.68 which is meaningfully higher
than the acquired F-distribution which equals to 2.016 at confidence in- 3.3. ANN modeling
terval of 95%. This issue proves the predicted strength of the fitted
model (Roohi et al., 2016). The F-value and P-value of lack-of-fit exam- In the current investigation, the ANN model contains four input var-
inations for the CCD model of SSZ removal is also mentioned in Table 3. iables including ozone concentration, initial H2O2 concentration, reac-
Based on these data it can be deduced that the P-value of lack-of-fit ex- tion time and initial concentration of pharmaceutical contaminant and
aminations is about 0.299 which is N0.05. This subject approves that the also one output factor of the drug degradation yield (%). Furthermore,
CCD model appropriately fits the experimental data and also data devi- the results of experimental data containing 31 sets was employed for
ations around the quadratic relationship of response surface is relatively training and validating of the ANN model which are reported in
insignificant in comparison with the pure error (KwonIm et al., 2012). Table 2. The selection of the number of neurons in hidden layer has re-
Table 3S reported the t-values and P-values of the main parameters markable effect on performance of the ANN model. In the present re-
and also their interactions. The lower quantity of P-value and the higher search, different numbers of neurons were examined, from 3 to 20, in
amount of t-value demonstrate that the variable related to this t-value the hidden layer. The diagram of the executed network is showed in
and P-value is more considerable parameter and consequently its influ- Fig. 4, where four input layer neurons linked to the four network
ence on the system response will be superior. According to Table 3S, the
second order term of reaction time and the original content of the SSZ [Ozone]*Time 0.00
contaminant and also all of the main factors are important terms of [Ozone]*[H2O2] 0.01
the model which have P-value b 0.05. [SSZ]*[SSZ] 0.02
The residual analysis which indicates the deviation among the ex- [SSZ]*Time 0.02
perimental data and the model-adjusted values facilitates the investiga- [H2O2]*Time 0.1
tion about the goodness-of-fit in both of regression and ANOVA. Fig. 2S [Ozone]*[Ozone] 0.16
illustrates the residual plots related to the residual data which was gen- Time*Time 0.19
erated by 31 experimental runs. This analysis contained the normal [H2O2]*[H2O2] 0.83
probability plot, residual versus fit, residual versus order and histogram [Ozone]*[SSZ] 1.72
plots. As it is evident by Fig. 2S, the tendency in all of the plots discloses
[H2O2] 1.79
that residuals possess a normal distribution. For instance, the normal
[H2O2]*[SSZ] 2.69
probability plot can be approximately considered as a straight line
[SSZ] 24.77
that approves the normal distribution of the residues. Additionally, the
Time 32.43
symmetry which is shown in the histogram plot verifies the normal dis-
[Ozone] 35.26
tribution of the results. The residual versus the fit plot and also the resid-
ual versus the order plot prove the independence of the residuals 0 5 10 15 20 25 30 35 40
because they are arbitrarily scattered on both sides of the zero line, Percentage effect of each factor
without representing any standard pattern. The distances of the points
Fig. 3. Pareto graphical analysis for O3/H2O2 removal efficiency of antibiotic sulfasalazine.
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446 7

Input layer Hidden layer Output layer 0.330 and 0.674 respectively. The experimental degradation efficiency
values, both training and validation, is compared with predicted value
to assess the accuracy of the ANN model and the results are shown in
Ozone concentration (mg/L) Figs. 3S and 4S. As it can be seen in Fig. 3S a satisfactory agreement
was observed among the empirical results and the ANN model-
predicted values. Also, Fig. 4S depicts the residuals of fittings for both
training and validation values for development of model in this study.
Initial H2O2 concentration (mM) On the basis of the results, the predicted results are very close to the ex-
perimental data of SSZ degradation. Therefore, the results reveal that
Predicted degradation efficiency of SSZ (%)
the ANN model can predict the effect of various parameters on removal
of contaminants from aqueous solution with high accuracy.
Reaction time (min)
Bias

3.3.2. Effect of operational variables on O3/H2O2 process

Initial SSZ concentration (mg/L)
Bias 3.3.2.1. Influence of ozone concentration in the reactor inlet. Figs. 5 and 6
represented the predicted results of CCD and ANN models respectively
by the contour plots and response surface plots of the sulfasalazine deg-
Fig. 4. The ANN optimized structure.
radation efficiency (% D) as the function of different operational param-
eters. As evidenced by results of CCD based on RSM in Fig. 5(a) and
input variables, the 6 hidden layer and the input layer with a neuron re- results of ANN model in Fig. 6(a), degradation efficiency of SSZ was in-
lated to the output variable. The ANN model contained three layers with creased at greater initial ozone concentration and also higher reaction
k-fold method and topology of 4:6:1 which was used to predicted the time in the O3/H2O2 process. By increasing the inlet ozone concentration
degradation efficiency of SSZ by O3/H2O2 process from aqueous in gas phase, the rate of mass transfer improves and leads to an increase
solution. for ozone concentration in the liquid phase. The enhancement of the SSZ
The weights of input, hidden and output layers and their biases for removal could be justified by the two-film theory. Based on this theory
the developed ANN model were presented in Table 4. The relative sig- by increasing the ozone concentration in the reaction zone, more ROSs
nificance of input factors associated to the output factor of the modeling especially •OH will be released according to Eq. (1). Hence, high
can be estimated by the weight matrix. amounts of ozone molecules and •OH are available to degrade the SSZ
contaminant. The results of the current investigation which demon-
3.3.1. Validation of AAN model strate increase in initial ozone concentration leads to a more capable
In order to evaluate the performance of the ANN model, the statisti- degradation of organic agents, were verified by the available literature
cal parameters such as coefficient of determination (R2), root-mean- (Fathinia and Khataee, 2015; Fathinia et al., 2016). The response surface
square error (RMSE) and mean-absolute error (MAE) factors were and contour plots in Figs. 5(b) and 6(b) demonstrated that by increasing
employed as the error functions to show the model accuracy. The fol- the ozone initial concentration in any concentration of SSZ, the degrada-
lowing equations are defined these parameters: tion efficiency will be increased. However, as can be seen from Figs. 5
(c) and 6(c) there is an optimum condition between of ozone concen-
Xn Xn n
ðyi −yi Þ2 − ð f i −yi Þ
2 tration and H2O2 concentration.
i¼1 i¼1 The plots shows that after a certain concentration of H2O2 the degra-
R2 ¼ P ðyi −yi Þ2 ð13Þ
i¼1 dation efficiency of SSZ decreases with an increase in the initial concen-
tration of H2O2 and the optimum area of operation parameters occurred
" #1=2
n 2 in the middle concentration of hydrogen peroxide. The cause of this
∑i¼1 ð f i −yi Þ
RMSE ¼ ð14Þ event can be related to Eq. (2) that will be more explained in
n
Section 3.3.2.2.

X
1 n
MAE ¼ j f −yi j ð15Þ
n i¼1 i 3.3.2.2. Effect of initial H2O2 concentration. By considering the role of H2O2
as the accelerator of •OH production and also •OH scavenger, in order to
where n, i, yi and fi indicate the number of experimental repetitions, the optimizing the SSZ removal system through the O3/H2O2 procedure the
index of data, the observed and predicted value, respectively. For the influence of insertion of H2O2 to the reaction media was investigated.
best trained ANN model, R2, MAE and RMSE were achieved 0.995, Figs. 5S and 6S shows the predicted result of CCD based of RSM and
ANN modeling for degradation efficiency of SSZ (% D) as a function of
Table 4 initial H2O2 concentration and reaction time. As it is displayed by fig-
Matrices of weights: W1: weights between the input and the hidden layers; W2: weights ures, the SSZ removal efficiency is gradually enhanced by adding of
between the hidden and the output layers.
H2O2 from 0.02 to about 0.14 mM while (although)with further increase
W1 W2 in the amount of H2O2 the SSZ removal efficiency decreased which it can
Variables
be due to the H2O2 scavengering effect. Increment in the concentration
Neuron Bias of H2O2 can promote the SSZ degradation efficiency, until the H2O2 con-
[O3] [H2O2] [SSZ] Reaction Neuron Weight
centration reach to the equilibrium with •OH, while excess H2O2 can act
(mg/L) (mM) (mg/L) time (min)
as •OH scavenger. On the other hands, H2O2 molecules can react with
1 0.298 24.510 −0.133 0.033 −2.42 1 10.620
•OH through the Eq. (2) and produce the hydroperoxide radicals
2 −0.427 −4.167 0.075 0.083 −1.02 2 5.195
3 −0.401 41.724 −0.063 −0.086 −0.46 3 −8.387 (HO2•). These radicals are less reactive with organic contaminants and
4 0.364 25.080 −0.031 −0.174 −0.36 4 −6.025 can consume the •OH generation according to Eq. (3). Thus the decrease
5 0.420 −25.782 0.120 −0.288 6.34 5 −0.940 in process efficiency is logical as a consequence of HO2• production. A
6 0.290 6.887 −0.104 0.019 −0.12 6 43.305 similar phenomenon has been described in previous investigations
Bias 27.547
with ciprofloxacin (Witte et al., 2009).
8 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

a 40
%D
< 15
35 15 – 30
30 – 45
Reaction time (min)
45 – 60

Degradation of SSZ (% D)
30
60 – 75
75 – 85
25 75
> 85
Hold Values 50
20 [H2O2]= 0.1 (mM)
[SSZ] = 15 (mg/L) 40
25
15 30
0
20
10 0..0
0
1 2 3 4 5 6 7 8 9 2.5
5.0 10
7.5
7
Ozone concentration (mg/L)

b 25
%D
Initial SSZ concentration(mg/L)

< 20
20 – 35
20 35 – 50

Degradation of SSZ (% D)
50 – 65
65 – 75 75
75 – 80
15 > 80 50
Hold Values
[H2O2] = 0.1 (mM) 25
10 Reaction time= 25 (min)
7.5
7.
0 5.0
6 2.5
5 12
1 2 3 4 5 6 7 8 9 18 0.0
24
Ozone concentration (mg/L)

c 0.18
%D
Initial H2O2 concentration (mM)

0.16 < 20
20 – 30
0.14 30 – 40
Degradation of SSZ (% D)

40 – 50
0.12 80
50 – 60
60 – 70
0.10 > 70 60
0.08 Hold Values
[SSZ] = 15 (mg/L) 40
0.06 Reaction time = 25 (min)
0.15
0.04 20 0.10
0.0 0.05
0.02 2.5
1 2 3 4 5 6 7 8 9 5.0 0.00
7.5
Ozone concentration (mg/L)

Fig. 5. The contour plots and response surface plots of the sulfasalazine degradation efficiency (% D) as the function of (a) ozone concentration (mg/L) and reaction time (min), (b) ozone
concentration (mg/L) and initial SSZ concentration (mg/L), (c) ozone concentration (mg/L) and H2O2 concentration (mM) predicted by CCD method.

3.4. Comparison of the ANN and CCD models

3.3.2.3. Effect of antibiotic sulfasalazine concentration on the ozone/H2O2
process. The contour and surface plots which show the effect of initial The CCD methodology has some advantages and the main one is
pharmaceutical (SSZ) concentration on the degradation efficiency that it determines contribution of variables via coefficients of the
(%) are depicted in Figs. 7S and 8S. As it was evident by figures, at quadratic regression model. Moreover, the CCD technique ade-
all of the initial SSZ concentrations, the degradation yield was suit- quately identifies the unimportant parameters, interactions among
ably improved by prolonging the reaction time. It can be realized the various variables and also the squared terms. Hence, the CCD
that, the degradation efficiency of SSZ was reduced by increasing methodology reduces the complication of the system. However, ac-
the initial SSZ concentration from 10 to 50 mg/L during 40 min of curate determination of the range of all parameters is inevitable in
O3/H2O2 process. In other words there is an indirect relation between the CCD approach. Alternatively, the ANN approach is an influential
SSZ initial concentration and the process efficiency. The reason could technique for modeling of the non-linear multi-variable systems in-
be attributed to decrease in probability of the reaction between oxi- cluding quadratic functions and almost all types of non-linear func-
dizing species and SSZ by increasing the initial SSZ concentration in tions whereas the CCD methodology is only suitable for quadratic
the aqueous media. Hence, the available ROSs are inadequate for approximation. Table 2 reported the estimated values by ANN and
the degradation of the SSZ and at higher concentrations only part CCD approaches and also Fig. 7 displayed the comparative parity
of them could interact with ROSs. As it is obvious from plots, the plot for predictions of ANN and CCD methodologies for experimental
yield of drug degradation is at its maximum value in the case of designs. As can be seen the data in Fig. 7 is depicted according to the
low drug concentrations. results of SSZ degradation yield (%) as mentioned in Table 2. In Fig. 7
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446 9

Predicted %D Predicted %D
45
< 30.0 90
40 68
< 35.0
46
35 < 40.0

Reaction time (min)

25
< 45.0 3
30 < 50.0
< 55.0
25 < 60.0
< 65.0
20
< 70.0
15 >= 70.0

10

5
0 2 4 6 8 10
Ozone Conc. (mg/L)
Predicted %D Predicted %D

25 < 30.0 81
Initial SSZ Conc. (mg/L)

< 35.0 61
< 40.0 42
23
20 < 45.0
4
< 50.0
< 55.0
15 < 60.0
< 65.0
< 70.0
10
>= 70.0

0 2 4 6 8 10
Ozone Conc. (mg/L)
Predicted %D Predicted %D
0.20
73
< 35.0 59
Initial H2O2 Conc. (mg/L)

< 40.0 45
0.15 < 45.0 31
< 50.0 17
< 55.0
0.10 < 60.0
< 65.0
< 70.0
>= 70.0
0.05

0.00
0 2 4 6 8 10
Ozone Conc. (mg/L)

Fig. 6. The contour plots and response surface plots of the sulfasalazine degradation efficiency (% D) as the function of (a) ozone concentration (mg/L) and reaction time (min), (b) ozone
concentration (mg/L) and initial SSZ concentration (mg/L), (c) ozone concentration (mg/L) and H2O2 concentration (mM) predicted by using ANN modeling.

all of the empirical data are appropriately compared with the pre-
dicted values by models (both of the ANN and CCD). On the basis of
the RMSE, MAE and R2 values, the suggested ANN and CCD models
for SSZ removal by O3/H2O2 process were appropriately compared.
The R2 value which was acquired by the CCD approach demonstrates
that the suggested quadratic polynomial equation suitably covered
99% variability of pharmaceutical degradation yield data. It means
that just 1% of variation is not described by the CCD technique. Re-
sults showed that the empirical data were satisfactorily fitted by
the CCD methodology with an adequate accuracy, while the results
of ANN technique exhibits greater deviation (3%) in comparison
with the CCD approach. The relative values of the factors of RMSE,
MAE and R2 are stated in Table 5.
The effect of the operational parameters on the yield of drug
degradation by the O 3/H2 O2 procedure is illustrated in Fig. 8
(a)–(d). For all of the figures, the model-predicted values (both of
CCD and ANN) and the empirical data were supplied. As it was
evident by these figures, an acceptable agreement is observed
through the model-predicted data and their corresponded experi-
mental results.
3.5. Optimum operating conditions for SSZ degradation efficiency
By using the response optimizer the optimal conditions of the
main parameters were successfully acquired and the results are
listed in Table 6. As the result it was inferred that the maximum
10 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

80 degradation yield of drug (98.10%) was productively obtained when

the values of each variable were accurately adjusted at their optimal
CCD modeling, R2 = 0.99 values. The value of pharmaceutical degradation efficiency which
70
was achieved at the optimal conditions was in acceptable agreement
ANN modeling, R2 = 0.97
with the predicted value from the CCD (98.69%) and ANN (96.34%)
Predicted value (%D)

60
model. This issue demonstrates that the optimization strategy
which was taken for the current system was appropriate in reaching
50 to the maximal degradation yield of the considered pharmaceutical
specially SNAs. Also, the highest degradation performance for SMX,
40 SMT and MNZ was achieved 89.34%, 86.29% and 58.70% respectively
at the optimum condition.
30

3.6. Elucidating the possible reaction mechanism in O3/H2O2 process

20
3.6.1. Effect of anionic ions and hydroxyl radical scavengers
10 The presence of anionic ions which usually found in real wastewater
10 20 30 40 50 60 70 80 containing pharmaceuticals can affect the degradation efficiency of
Experimental value (%D) AOPs in wastewater processes. Since, the effect of inorganic salts includ-
ing Na2SO4, NaH2PO4, Na2CO3, NaCl and tert butanol (TBA) as organic
Fig. 7. Comparison between the predicted (CCD and ANN) values and the actual results for •OH scavenger was studied on the SSZ degradation. These scavengers
SSZ degradation efficiency (%) under O3/H2O2 process. were added separately to the reactor while the other parameters kept
in their optimum values and the results are shown in Fig. 9. According
Table 5 these results, a significant decrease about of 56.53% and 49.41% in the
Characteristic and statistical parameters of CCD and ANN. degradation efficiency of SSZ was found in the presence of TBA and
Parameters CCD model ANN model NaCl respectively. The high reduction of these molecules in contrast of
Regression coefficient (R2) 0.99 0.97
another scavengers could be attributed to the high reactivity ability of
Mean absolute error (MAE) 0.850 1.57 the TBA (k = 6 × 108 M−1s−1) and NaCl (k = 4.3 × 109 M−1s−1)
Root Mean square error (RMSE) 1.15 2.04 with •OH and H2O2 molecule (Eqs. (16)–(18)) (Liao et al., 2001;

80 60

Experimental data (a) Experimental data (b)

70
Degradation of SSZ (%)

CCD modeling CCD modeling

Degradation of SSZ (%)

55
60 ANN modeling ANN modeling

50 50

40
45
[H2O2]0 = 0.1 mM [O3] = 5 mg/L
30 [SSZ]0 = 15 mg/ L [SSZ]0 = 15 mg/ L
Reaction time = 25 min Reaction time = 25 min
20 40
1 3 5 7 9 0.02 0.07 0.12 0.17
Ozone concentration (mg/L) Initial H2O2 concentration (mM)
75
(c) (d)
70
Experimental data Experimental data
Degradation of SSZ (%)

65
Degradation of SSZ (%)

CCD modeling CCD modeling

60
ANN modeling 55 ANN modeling

50
45

40 [O3] = 5 mg/L 35 [O3] = 5 mg/L

[H2O2]0 = 0.1 Mm [H2O2]0 = 0.1 mM
Reaction time = 25 min [SSZ]0 = 15 mg/ L
30 25
5 10 15 20 25 10 15 20 25 30 35 40
Initial SSZ concentration (mg/L) Reaction time (min)

Fig. 8. Comparison between predicted (CCD and ANN) and experimental values of the SSZ degradation efficiency (%) as a function of (a) Ozone concentration (mg/L), (b) Initial H2O2
concentration (mM), (c) Initial SSZ concentration (mg/L), (d) Reaction time (min).
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446 11

Table 6 Ortega-Liébana et al., 2012; Khataee et al., 2016). These results indicate
Optimal values of the process parameters for the maximum degradation (%). that •OH and H2O2 molecule play an important role in the oxidation of
Removal efficiency of SSZ SSZ molecule.
(%)
[O3]0 [H2O2]0 [SSZ]0 Reaction time
ðCH3 Þ3 COH þ ˙OH→H2 O þ CH2 CðCH3 Þ2 OH ð16Þ
(mg/L) (mM) (mg/L) (min) Predicted
Experimental
−
CCD ANN
Cl þ ˙OH→˙ClOH− ð17Þ
9 0.078 5 40 98.10 98.69 96.34
−
˙Cl þ H2 O2 →Hþ þ Cl þ HO˙2 ð18Þ

As can be observed from Fig. 12, SSZ removal was decreased in pres-
ence of Na2CO3 to 60.45% while the reduction of efficiency after addition
100 of Na2SO4 was 71.53%. According to Eq. (19) the produced CO2− 3 react
98.1
with hydroxyl radicals and created the CO•−3 which are the weekly oxi-
dant, thus the degradation efficiency of SSZ decreased (Khataee et al.,
78.08
80 2017). Similarly, the sulfate ions can scavenge •OH and produce the
Degradation Efficiency (%)

SO•−
71.53
4 radicals that have oxidation potential of 2.6 V (Eqs. (20))
60.45
(Darvishi et al., 2014).
60
˙− −
48.9 CO2−
3 þ ˙OH→CO3 þ OH ð19Þ
41.78
˙− −
40 SO2−
4 þ ˙OH→SO4 þ OH ð20Þ

Also, after the introduction of NaH2PO4 to the medium of reaction the

20
SSZ degradation efficiency decreased from 98.10 to 78.08%. The high rate
constant of phosphate with •OH (1.2 × 107 M−1 s−1) make phosphate
ions as a free radical scavengers and hence •OH reacts with phosphate in-
stead of SSZ molecules (Beltran et al., 2008; Xu et al., 2014).
0
No TBA NaCl Na2CO3 Na2SO4 NaH2PO4
Scavenger 3.6.2. Analysis of produced intermediates and proposed degradation
pathway
Fig. 9. Scavenging test on SSZ during of O3/H2O2 process [SSZ]0 = 5 mg/L, [H2O2] =
Only few researches have been reported to intermediated product of
0.8 mM, [ozone]0 = 9 mg/L, [scavengers]0 = 48 mg/L, pH = 7 and Reaction time = SNAs especially SSZ degradation in AOPs. Protonated molecular ions [M-
40 min. H] + were chosen as the probable parent ions. Some of the MS/MS spec-
tra of the new aromatic products are presented in Fig. 10. Also, Fig. 11

Fig. 10. Accurate MS/MS spectra and fragmentation routes for some of the new SSZ transformation products.
12 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

summarizes the characteristics of all oxidation by-products (31 species)
which were formed and then destroyed during O3/H2O2 process. Based
on these detected species and intermediate products, two main reaction
pathways were proposed for the degradation of SSZ molecule by •OH/O3
oxidative. As it is evident from Fig. 11 degradation of SSZ was initiated at
2-position: first the attack of hydroxyl radical to the azo-group (path-
way 1) and the second attack to sulfonamides groups (pathway
2) resulting in cleavage of the N_N and N-S bonds respectively. In path-
way 1, the molecular ion of SSZ (m/z = 399) degraded to intermediate
of with m/z of 282. Afterwards, according to the reactions of pathway 1,
the intermediate with m/z of 191 (C5H6N2SO4) and 159 (C5H6N2SO2)
was identified as a result of cleavage bound between benzene and sul-
fur. Further hydroxylation of bonds are resulted in the breakage bounds
between of sulfur and nitrogen in the molecules and generation of
amino pyridines and hydroxyl pyridine rings with m/z of 126 and 95 re-
spectively. Finally, undergo further reaction of ROSs with these rings the
end-products such as including CO2, water and inorganic ions were
achieved. In another way (pathway 2), according to the reactivity of hy-
droxyl radicals, multiple hydroxylation reactions occurred during the
cleavage bound of between of N-S, which leads to structures of the
kind of product (A) and (B). In the case of by-product of way A the
desulfonation reactions was occurs which led to generate the molecules
such as salicylic acid (m/z = 139 for [M + H] +). Another results from
the hydroxylation of bound N-S in the pathway 2 are given in ways of
2B. Compounds of pathway 2B which are results of the attack of hy-
droxyl radical on the azo-group induces the generation of intermediate
such as sulphanilic acid with m/z of 174 which reported in previous of
studies as a by-product of degradation of sulfonamides antibiotics
with AOPs (Boreen et al., 2004; Bonvin et al., 2013; Shahmahdia et al.,
2020). In the following undergo further reaction the cleavage of S\\C
bonds and release of SO2−4 ions were happened which led to the forma-
tion of benzoquinone molecule. Ultimately, through a series of

Sulfasalazine COOH
N O

NH S N N OH

O
m/z=399

OH OH OH OH OH OH
NH2
HOOC HOOC HOOC HOOC HOOC HOOC
OH

OH
N N N N N N
O S O
N N N
(2A) N N N
HN
Desulfonation OH
HO

O S O O S O O S O OH OH
NH2 OH H m/z = 275 m/z=259 m/z=243 m/z=282
m/z=338 m/z=323 m/z=308
(2B) Azo bond cleavage
(2A')
NH NHOH NHOH OH OH OH OH
2 OH H
HO OH HOOC OH O
O S O O S

NH NH
OH

O S O O S O O S O O S O NH2
O S O
NH2 NHOH OH NH2 m/z=139 m/z=126 N N
OH OH
m/z=205 m/z=205 m/z=185 m/z=174 m/z=191 m/z=159 m/z=191
(2A'')
OH O COOH
OH
(2B')
OH OH

N N
O S O O S O O S O O OH
O S O
NH2 H OH OH NH2
H
m/z=158 m/z=159 m/z=143 m/z=159 m/z= 95 m/z=109 m/z=123
m/z=126 m/z=111

(2B'')
OH O OH OH NH2
OH
N

N N

O NH2 •OH O O
m/z= 95 m/z=109 m/z=126 m/z=95 m/z=111 m/z=95

- O O
C O
O O S - N O
O O +
O O- - N - H H
O O

Fig. 11. Proposed possible degradation pathways of SSZ by O3/H2O2 process.

 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446 13

(a) (b)

Carbon
Oxygen
Nitrogen
Sulphur
Hydrogen

(c) (d)

Fig. 12. The optimized (a) SSZ, (b) SMX, (c) SMZ and (d) MNZ molecule structures with atom numbering.

Table 7
Nucleophilic (P− +
k ) and electrophilic (Pk ) values of atoms on SSZ molecules.

No. Atoms P−
k P+
k No. Atoms P−
k P+
k No. Atoms P−
k P+
k

1 C1 −0.041 0.165 11 C14 0.065 0.143 21 C29 −0.002 −0.004

2 C2 0.090 −0.092 12 C15 −0.059 0.060 22 C30 0.003 0.004
3 C3 0.150 0.154 13 C17 −0.043 −0.087 23 N32 −0.002 0.001
4 C4 0.023 −0.022 14 C19 0.138 0.124 24 C34 0.012 −0.000
5 C5 0.060 0.103 15 S22 −0.009 0.012 25 O37 0.127 0.015
6 C6 0.222 −0.131 16 O23 0.000 0.000 26 C39 0.003 −0.002
7 N10 −0.039 0.324 17 O24 0.002 −0.000 27 O40 0.006 −0.006
8 N11 0.089 0.190 18 N25 0.039 0.009 28 O41 0.000 −0.000
9 C12 0.058 −0.016 19 C27 0.037 −0.008
10 C13 0.096 0.074 20 C28 −0.006 0.005

oxidation steps these molecules were mineralized and converted to in-
organic products (e.g., CO2 and water).
3.6.3. DFT calculations
DFT calculations were used to help analyze the structure of antibi-
otics, determine the degradation pathway, and reveal the degradation
mechanism. The degradation of SSZ, SMX, SMZ and MNZ by H2O2/O3
(•OH/O3) system involves a complex oxidation process with both nucle-
ophilic and electrophilic reactions. Therefore, electrophilic and nucleo-
philic Parr Functions was selected to describe the vulnerable sites of
SSZ, SMX, SMZ and MNZ molecules. The optimized SSZ, SMX, SMZ and
MNZ molecules are depicted in Fig. 12, and the calculated Pk values
are listed in Tables 7, 8, 9 and 10 respectively. Generally, the most pos-
itive P− +
k and Pk values usually indicates that a specific atom is the most
susceptible to be attacked by nucleophilic and electrophilic oxidative
species, respectively. For example, the most positive P+ k value of the
10(N) and 11(N) in Table 7 suggested that the 10(N) and 11(N) of
SSZ were the most susceptible site to attack by electrophilic species
such as •OH. This attack might lead to the cleavage of the azo-group
and resulting in cleavage of the N_N bonds. These results are in accor-
dance with results of LC-MS studies in the pathways of SSZ degradation.
Meanwhile, 6(C) and 19(C) also showed high susceptibility to attack by
nucleophilic species, which might lead to the cleavage of the bonds of 19

Table 9
Table 8 Nucleophilic (P− +
k ) and electrophilic (Pk ) values of atoms on SMT molecules.
Nucleophilic (P− +
k ) and electrophilic (Pk ) values of atoms on SMX molecules.
No. Atoms P−
k P+
k No. Atoms P−
k P+
k
No. Atoms P−
k P+
k No. Atoms P−
k P+
k
1 C1 0.076 0.207 11 N18 0.029 0.178
1 C1 0.172 0.535 10 C17 −0.000 0.043 2 C2 0.173 −0.039 12 N19 0.031 0.181
2 C2 −0.102 0.216 11 C18 −0.001 −0.010 3 C3 −0.078 0.121 13 C20 −0.018 0.390
3 C3 0.359 0.157 12 N19 0.038 0.012 4 C4 0.317 −0.006 14 C21 −0.014 0.409
4 C4 −0.135 −0.013 13 C20 0.004 0.063 5 C5 −0.105 −0.024 15 C22 0.062 −0.196
5 C5 0.234 0.054 14 O22 0.003 −0.003 6 C6 0.168 −0.170 16 O24 0.012 −0.000
6 C6 0.049 0.124 15 C23 −0.001 −0.040 7 S11 −0.045 0.024 17 O25 0.023 −0.003
7 N11 0.369 −0.006 16 O27 0.029 −0.003 8 N12 0.323 −0.018 18 C26 0.000 −0.050
8 S14 −0.039 −0.095 17 O28 0.015 0.019 9 N15 0.096 −0.003 19 C30 −0.003 −0.040
9 N15 0.045 0.000 10 C17 −0.008 −0.070
14 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446

Table 10 relatively high susceptibility to cleavage or oxidation. In about of SMZ

Nucleophilic (P− +
k ) and electrophilic (Pk ) values of atoms on MNZ molecules. molecule, as shown in Table 9 the 2(C), 4(C) and 6(C) on the rings,
No. Atoms P−
k P+
k No. Atoms P−
k P+
k
and 12(N) of the amino group exhibited relatively high susceptibility
1 C1 0.339 0.071 7 C8 −0.021 −0.009
to cleavage and/or oxidation. Also, in this molecule the high P+k values

2 C2 0.251 0.188 8 O12 0.186 0.245 for 20(C) and 21(C) indicated the bond cleavage between these atoms
3 C3 0.435 −0.049 9 O13 −0.099 0.220 and methyl groups (20(C)-26(c) and 21(C)-30(C)). A preliminary anal-
4 N4 −0.044 0.059 10 C14 −0.002 0.009 ysis of the data given in Table 10 indicates that cleavage of bounds of
5 N6 −0.040 −0.040 11 C17 0.005 −0.004
MNZ molecule mostly happens in 1(C), 2(C) and 3(C). Also, these re-
6 N7 −0.050 0.303 12 O20 0.000 0.000
sults show that the most favored atoms attacked by electrophilic oxida-
tive species could be on the nitro group (12(O), 13(O) and 7(N)) of MNZ
(C)-22(S) and 6(C)-10(N) and production of A (desulfonation) and B molecule (the highest value of P+ k ).
(azo bond cleavage) structures in pathway 2. Consequently, the attacks In the end, it was investigated that the attack of •OH on N_N bond is
predicted by Parr function were appropriately observed by LC-MS preferable, hence the need to talk about the cleavage of the N\\N bond
studies. in SSZ molecule. The Fig. 13 investigated the degradation of azo group of
With respect to SMX, the results in Table 8 show that the 1(C), 2 SSZ molecule by •OH produced from H2O2/O3 process and concluded
(C) and 6(C) on the six-membered ring was most probable to be that the initial attack by OH radicals can be occurred at the N atoms
attacked with electrophilic oxidative species, and the 3(C), 5(C) and bearing the azo linkage. Also, Fig. 14 represents the potential energy
11(N) were also susceptible to nucleophilic attack which exhibited profile of the DFT modeled mechanism for the N_N bond cleavage

1: Sulfasalazine & OH 2N TS (2N-3N)

3N TS (3N-4N) 4N

TS (4N-5N, 6N) 5N 6N

Fig. 13. Optimized geometries for the N\

\N cleavage pathway.

15
TS (3N-4N)
10
TS (4N-5N,6N)
Energy (kcal/mol)

5 Reactants
1 11.64
0
0.00 3.13 5N,6N
-5
2N TS (2N-3N) -4.08
-10 -8.20 -7.88
3N
-15
-15.38
-20 4N

-25

-30 -25.89
Reaction coordinate

Fig. 14. The computed potential energy profile along the N\

\N bond cleavage pathway.
 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446
pathway of SSZ (1) (Fig. 13). A prereaction complex (2N) is observed as
the •OH approaches to the SSZ molecule. Formation of the transition
state structure (TS(2N-3N), potential energy = −7.88 kcal/mol) was
happened. In the continues of reactions the H atom of the OH group ap-
proaches the neighboring N atom, forming a cyclic transition state struc-
ture (TS(3N-4N)) with the most potential energy (11.64 kcal/mol). This
potential energy indicating this reaction can proceed smoothly and effi-
ciently at room temperature. The breakage of O\\H and the formation of
N\\H bond leading to another radical intermediate (4N). Consequently,
weakening of the –N=N– bond results in cleavage of the SSZ molecule
into the byproducts ((5N) and (6N)) via the transition state (TS(4N-
5N,6N)), potential energy = 3.13 kcal/mol).
4. Conclusion
In this research, the degradation of SNAs such as SSZ, SMX, SMT and
MNZ as an inflammatory bowel disease were investigated firstly in
aqueous media by O3/H2O2 process. The empirical kinetic studies of
the process estimated a pseudo-first-order reaction for all of cases.
Also, modeling and optimization of SNAs degradation namely SSZ was
exhibited using CCD based RSM and ANN approaches. The results of
CCD led to a second order quadratic model with acceptable P-value
and a lack-of-fit value less than and N0.05, respectively. ANN model
with topology of 4:6:1 was applied to model SSZ degradation efficiency
by O3/H2O2 process. The experimental data was compared with CCD
and ANN outcomes which demonstrated that CCD predicted values
were in good agreement with the experimental data (R2 = 0.99,
RMSE = 1.15 and MAE = 0.85) in contrast of ANN predicted value
(R2 = 0.97, RMSE = 2.04 and MAE = 1.57). Maximum degradation
yield of 98.69%, 96.34% and 98.10% were predicted and experimentally
validated with RSM, ANN and empirical data, respectively. The ANOVA
and Pareto analysis resulted from CCD demonstrated that ozone con-
centration with a percentage effect of 35.26% was as the effective pa-
rameter on SSZ degradation in the O3/H2O2 process. Optimization
results showed that the highest treatment performance for SSZ, SMX,
SMT and MNZ was achieved 98.10%, 89.34%, 86.29% and 58.70% respec-
tively at the optimum condition including ozone concentration of
9 mg/L, initial H2O2 concentration of 0.08 mM, initial SSZ concentration
of 5 mg/L and reaction time of 40 min. The presence of inorganic salts
including Na2SO4, NaH2PO4, Na2CO3, NaCl and tert butanol (TBA) as or-
ganic •OH scavenger in O3/H2O2 process decrease degradation efficiency
of SSZ. LC-(+ESI)-MS/MS technology was employed to identify aro-
matic products formed (31 intermediates) during the degradation of
SSZ solutions under optimal conditions of O3/H2O2 process. Also, DFT
calculations were used to help analyze the structure of antibiotics, de-
termine the degradation pathway, and reveal the degradation mecha-
nism. Based on these detected species and DFT computational, two
main reaction route were proposed for the degradation of SSZ molecule
by •OH/O3 oxidative. Degradation of SSZ was initiated at 2-position: first
the attack of hydroxyl radical to the azo-group (pathway 1) and the sec-
ond attack to sulfonamides groups (pathway 2) resulting in cleavage of
the N_N and N-S bonds respectively. The methodology supporting the
research experimentation for optimizing removal of SNAs may be useful
in design of protocols for practical engineering water decontamination
applications.
CRediT authorship contribution statement
Rasool Pelalak: Conceptualization, Investigation, Formal analysis,
Writing - original draft, Writing - review & editing. Reza Alizadeh:
Conceptualization, Investigation, Formal analysis, Writing - original
draft, Writing - review & editing. Eslam Ghareshabani: Conceptualiza-
tion, Formal analysis. Zahra Heidari: Conceptualization, Investigation,
Writing - original draft, Writing - review & editing.
15
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
Acknowledgements
The authors are grateful to Sahand University of Technology for their
financial supports of the research.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.scitotenv.2020.139446.
References
Agbaba, J., Dalmacija, B., Tubić, A., Molnar, J., 2010. Advanced Oxidation Processes for
Water Treatment, Voda i Sanitarna Tehnika. 40 pp. 11–30.
Alizadeh Kordkandi, S., Mohaghegh Motlagh, A., 2018. Optimization of peroxone reaction
rate using metaheuristic approach in the dearomatization and discoloration process.
Environ. Prog. Sustain. Energy 37, 695–702.
Andreozzi, R., Caprio, V., Insola, A., Marotta, R., 1999. Advanced oxidation processes (AOP)
for water purification and recovery. Catal. Today 53, 51–59.
Baran, W., Adamek, E., Ziemiańsk, J., Sobczak, A., 2011. Effects of the presence of sulfon-
amides in the environment and their influence on human health. J. Hazard. Mater.
196, 1–15.
Beltran, F.J., Aguinaco, A., Garcı’a-Araya, J.F., Oropes, A., 2008. Ozone and photocatalytic
processes to remove the antibiotic sulfamethoxazole from water. Water Res. 42,
3799–3808.
Bonvin, F., Omlin, J., Rutler, R., Schweizer, W.B., Alaimo, P.J., Strathmann, T.J., McNeill, K.,
Kohn, T., 2013. Direct photolysis of human metabolites of the antibiotic sulfamethox-
azole: evidence for abiotic back-transformation. Environ. Sci. Technol. 47, 6746–6755.
Boreen, A.L., Arnold, W.A., McNeill, K., 2004. Photochemical fate of sulfa drugs in the
aquatic environment:sulfa drugs containing five-membered heterocyclic groups. En-
viron. Sci. Technol. 38, 3933–3940.
Cruz-Alcalde, A., Esplugas, S., Sans, C., 2020. Continuous versus single H2O2 addition in
peroxone process: performance improvement and modelling in wastewater efflu-
ents. J. Hazard. Mater. 387, 121993.
Darvishi, R., Soltani, Cheshmeh, Rezaee, A., Khataee, A.R., Safari, M., 2014. Photocatalytic
process by immobilized carbon black/ZnO nanocomposite for dye removal from
aqueous medium: optimization by response surface methodology. J. Ind. Eng.
Chem. 20, 1861–1868.
Domingo, Luis R., Pérezb, P., Sáez, J.A., 2013. Understanding the local reactivity in polar or-
ganic reactions through electrophilic and nucleophilic Parr functions. RSC Adv. 3,
1486–1494.
Elmolla, E.S., Chaudhuri, M., Eltoukhy, M.M., 2010. The use of artificial neural network
(ANN) for modeling of COD removal from antibiotic aqueous solution by the Fenton
process. J. Hazard. Mater. 179, 127–134.
Fathinia, M., Khataee, A., 2015. Photocatalytic ozonation of phenazopyridine using TiO2
nanoparticles coated on ceramic plates: mechanistic studies, degradation intermedi-
ates and ecotoxicological assessments. Appl. Catal. A Gen. 491, 136–154.
Fathinia, M., Khataee, A., Aber, S., Naseri, A., 2016. Development of kinetic models for pho-
tocatalytic ozonation of phenazopyridine on TiO2 nanoparticles thin film in a mixed
semi-batch photoreactor. Appl. Catal. B Environ. 184, 270–284.
Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R.,
Scalmani, G., Barone, V., Petersson, G.A., Nakatsuji, H., Li, X., Caricato, M., Marenich,
A.V., Bloino, J., Janesko, B.G., Gomperts, R., Mennucci, B., Hratchian, H.P., Ortiz, J.V.,
Izmaylov, A.F., Williams, J.L.S., Ding, F., Lipparini, F., Egidi, F., Goings, J., Peng, B.,
Petrone, A., Henderson, T., Ranasinghe, D., Zakrzewski, V.G., Gao, J., Rega, N., Zheng,
G., Liang, W., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M.,
Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Throssell, K., Jr, J.A.M.,
Peralta, J.E., Ogliaro, F., Bearpark, M.J., Heyd, J.J., Brothers, E.N., Kudin, K.N.,
Staroverov, V.N., Keith, T.A., Kobayashi, R., Normand, J., Raghavachari, K., Rendell,
A.P., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Millam, J.M., Klene, M., Adamo, C.,
Cammi, R., Ochterski, J.W., Martin, R.L., Morokuma, K., Farkas, O., Foresman, J.B.,
Fox, D.J., 2016. Gaussian 16 Revision A.03, Wallingford CT.
Gil, A., Galeano, L.A., Vicente, M.Á., 2018. Applications of Advanced Oxidation Processes
(AOPs) in Drinking Water Treatment. Springer International Publishing.
Gurol, M.D., Vatistas, R., 1987. Oxidation of phenolic compounds by ozone and ozone+
UV radiation: a comparative study. Water Res. 21, 895–900.
Heidari, Z., Alizadeh, R., Ebadiab, A., Oturan, N., A.Oturan, M., 2020. Efficient photocatalytic
degradation of furosemide by a novel sonoprecipited ZnO over ion exchanged
clinoptilolite nanorods. Sep. Purif. Technol. 242, 116800.
Hosseini, S.A., Abbasian, A.R., Gholipoor, O., Ranjan, S., Dasgupta, N., 2019. Adsorptive re-
moval of arsenic from real sample of polluted water using magnetic GO/ZnFe2O4
nanocomposite and ZnFe2O4 nanospinel. Int. J. Environ. Sci. Technol. 16, 7455–7466.
Ingerslev, F., Halling-Sørensen, B., 2000. Biodegradability properties of sulfonamides in ac-
tivated sludge. Environ. Toxicol. Chem. 19, 2467–2473.
16 R. Pelalak et al. / Science of the Total Environment 734 (2020) 139446
Khataee, A.R., Zarei, M., Moradkhannejhad, L., 2010. Application of response surface meth-
odology for optimization of azo dye removal by oxalate catalyzed photoelectro-
Fenton process using carbon nanotube-PTFE cathode. Desalination 258, 112–119.
Khataee, A., Gholami, P., Vahid, B., 2016. Heterogeneous sono-Fenton-like process using
nanostructured pyrite prepared by Ar glow discharge plasma for treatment of a tex-
tile dye. Ultrason. Sonochem. 29, 213–225.
Khataee, A., Gholami, P., Vahid, B., 2017. Catalytic performance of hematite nanostruc-
tures prepared by N2 glow discharge plasma in heterogeneous Fenton-like process
for acid red 17 degradation. J. Ind. Eng. Chem. 50, 86–95.
KwonIm, J., HyoungCho, I., KyuKim, S., DukZoh, K., 2012. Optimization of carbamazepine
removal in O3/UV/H2O2 system using a response surface methodology with central
composite design. Desalination 285, 306–314.
Lambropoulou, D., Evgenidou, E., Saliverou, V., Kosma, C., Konstantinou, I., 2017. Degrada-
tion of venlafaxine using TiO2/UV process: kinetic studies, RSM optimization, identi-
fication of transformation products and toxicity evaluation. J. Hazard. Mater. 323,
513–526.
Lei, K., Zhu, Y., Chen, W., Pan, H.-Y., Cao, Y.-X., Zhang, X., Guo, B.-B., Sweetman, A., Chun-
YeLina, Ouyang, W., He, M.-C., Liu, X.-T., 2019. Spatial and seasonal variations of anti-
biotics in river waters in the Haihe River Catchment in China and ecotoxicological risk
assessment. Environ. Int. 130.
Li, P., Guo, M., Wang, Q., Li, Z., Wang, C., Chen, N., Wang, C.-C., Wan, C., Chen, S., 2019. Con-
trollable synthesis of cerium zirconium oxide nanocomposites and their application
for photocatalytic degradation of sulfonamides. Appl. Catal. B Environ. 259.
Liancai, A., Jiufang, H., Yinghui, Z., Xianhe, B., 2018. Research and application progress on
porous organic polymers for adsorption and separation of organic pollutants in water
system. Chin. J. Appl. Chem. 35, 1019–1025.
Liao, Chih-Hsiang, Kang, Shyh-Fang, Wu, Fu-An, 2001. Hydroxyl radical scavenging role of
chloride and bicarbonate ions in the H2O2/UV process. Chemosphere 44, 1193–1200.
Mansouri, L., Tizaoui, C., Geissen, S.-U., Bousselmi, L., 2019. A comparative study on ozone,
hydrogen peroxide and UV based advanced oxidation processes for efficient removal
of diethyl phthalate in water. J. Hazard. Mater. 363, 401–411.
Moussavi, G., Yazdanbakhsh, A., Heidarizad, M., 2009. The removal of formaldehyde from
concentrated synthetic wastewater using O3/MgO/H2O2 process integrated with the
biological treatment. J. Hazard. Mater. 171, 907–913.
Munter, R., 2001. Advanced oxidation processes–current status and prospects. Proc.
Estonian Acad. Sci. Chem. 50, 59–80.
Myers, R.H., Montgomery, D.C., Anderson-Cook, C.M., 2011. Response Surface Methodol-
ogy: Process and Product Optimization Using Designed Experiments. Wiley.
Ortega-Liébana, M.C., Sánchez-López, E., Hidalgo-Carrillo, J., Marinas, A., Marinas, J.M.,
Urbano, F.J., 2012. A comparative study of photocatalytic degradation of 3-
chloropyridine under UV and solar light by homogeneous (Photo-Fenton) and het-
erogeneous (TiO2) photocatalysis. Appl. Catal. B Environ. 127, 316–322.
Oturan, M.A., Aaron, J.J., 2014. Advanced oxidation processes in water/wastewater treat-
ment: principles and applications. Environ. Sci. Technol. 44, 2577–2641.
Ozen, A.S., Aviyente, V., 2003. Modeling the oxidative degradation of azo dyes: a density
functional theory study. J. Phys. Chem. A 107, 4898–4907.
Pelalak, R., Heidari, Z., 2014. Lithographically cut multiwalled carbon nanotubes: opening
caps, controlling length distribution, and functionalization. J. Disper. Sci. Technol. 35,
808–814.
Pelalak, R., Baniadam, M., Maghrebi, M., 2013. Controllable purification, cutting and
unzipping of multi-walledcarbon nanotubes with a microwave method. Appl. Phys.
A 111, 951–957.
Pelalak, R., Alizadeh, R., Ghareshabani, E., 2020. Enhanced heterogeneous catalytic ozona-
tion of pharmaceutical pollutants using a novel nanostructure of iron-based mineral
prepared via plasma technology: a comparative study. J. Hazard. Mater. https://doi.
org/10.1016/j.jhazmat.2020.122269.
Peng, C., Schlegel, H.B., 1993. Combining synchronous transit and quasi-Newton methods
to find transition states. Isr. J. Chem. 33, 449–454.
Qiao, M., Ying, G.-G., Singer, A.C., Yong-GuanZhu, 2018. Review of antibiotic resistance in
China and its environment. Environ. Int. 110, 160–172.
Qin, L.T., Pang, X.R., Zeng, H.H., Liang, Y.P., Mo, L.Y., Wang, D.Q., Dai, J.F., 2019. Ecological
and human health risk of sulfonamides in surface water and groundwater of Huixian
karst wetland in Guilin, China. Sci. Total Environ. 134552.
Rabølle, M., HenrikSpliid, N., 2000. Sorption and mobility of metronidazole, olaquindox,
oxytetracycline and tylosin in soil. Chemosphere 40, 715–722.
Roohi, P., Fatehifar, E., Alizadeh, R., 2016. Mathematical modeling and optimization of
sonication remediation of soil polluted with 2-methylpropane-2-thiol. Adv. Environ.
Technol. 1, 137–146.
Russell, D.L., 2006. Practical Wastewater Treatment. Wiley.
Sahoo, C., Gupta, A.K., 2012. Optimization of photocatalytic degradation of methyl blue
using silver ion doped titanium dioxide by combination of experimental design and
response surface approach. J. Hazard. Mater. 216, 302–310.
Samarb, S., Birgani, Y., Yazdani, M., AkbarBabaei, A., 2019. A comparative removal of two
dyes from aqueous solution using modified oak waste residues: process optimization
using response surface methodology. J. Ind. Eng. Chem. 73, 67–77.
Shahmahdia, N., Dehghanzadeh, R., Aslania, H., Shokouhi, S.B., 2020. Performance evalua-
tion of waste iron shavings (Fe0) for catalytic ozonation in removal of sulfamethoxa-
zole from municipal wastewater treatment plant effluent in a batch mode pilot plant.
Chem. Eng. J. 383, 123093–123106.
Shirazian, S., Ismail, H.Y., Singh, M., Shaikh, R., Croker, D.M., Walker, G.M., 2019. Multi-
dimensional population balance modelling of pharmaceutical formulations for con-
tinuous twin-screw wet granulation: determination of liquid distribution. Int.
J. Pharm. 566, 352–360.
Witte, B., Dewulf, J., Demeestere, K., Langenhove, H., 2009. Ozonation and advanced oxi-
dation by the peroxone process of ciprofloxacin in water. J. Hazard. Mater. 161,
701–708.
Xu, M., Gu, X., Lu, S., Qiu, Z., Sui, Q., 2014. Role of reactive oxygen species for 1, 1, 1-
trichloroethane degradation in a thermally activated persulfate system. Ind. Eng.
Chem. Res. 53, 1056–1063.
Yu, L., Song, C., Zhang, C., Fan, L., Qiu, L., Wu, W., Meng, S., Hu, G., Chen, J., 2018. Occur-
rence of sulfonamides in fish in the lower reaches of Yangtze River, China and esti-
mated daily intake for understanding human dietary exposure. Aquaculture 495,
538–544.
Yuan, B., Xu, D., Li, F., Fu, M.-L., 2013. Removal efficiency and possible pathway of odor
compounds (2-methylisoborneol and geosmin) by ozonation. Sep. Purif. Technol.
117, 53–58.
Zarei, M., Khataee, A., Ordikhani-Seyedlar, R., Fathinia, M., 2010. Photoelectro-Fenton
combined with photocatalytic process for degradation of an azo dye using supported
TiO2 nanoparticles and carbon nanotube cathode: neural network modeling.
Electrochim. Acta 55, 7259–7265.
Zhao, Y., Truhlar, D.G., 2008. The M06 suite of density functionals for main group thermo-
chemistry, thermochemical kinetics, noncovalent interactions, excited states, and
transition elements: two new functionals and systematic testing of four M06-class
functionals and 12 other functionals. Theor. Chem. Accounts 120, 215–241.
Zhou, Z., Liu, X., Sun, K., Lin, C., Ma, J., He, M., Ouyang, W., 2020. Persulfate-based advanced
oxidation processes (AOPs) for organiccontaminated soil remediation: a review.
Chem. Eng. J. 372, 836–851.