Highly efficient UV/H2O2 technology for the removal of nifedipine antibiotics: Kinetics, co-existing anions and degradation pathways

This study investigates the degradation of nifedipine (NIF) by using a novel and highly efficient ultraviolet light combined with hydrogen peroxide (UV/H2O2). The degradation rate and degradation kinetics of NIF first increased and then remained constant as the H2O2 dose increased, and the quasi-percolation threshold was an H2O2 dose of 0.378 mmol/L. An increase in the initial pH and divalent anions (SO42- and CO32-) resulted in a linear decrease of NIF (the R2 of the initial pH, SO42- and CO32- was 0.6884, 0.9939 and 0.8589, respectively). The effect of monovalent anions was complex; Cl- and NO3- had opposite effects: low Cl- or high NO3- promoted degradation, and high Cl- or low NO3- inhibited the degradation of NIF. The degradation rate and kinetics constant of NIF via UV/H2O2 were 99.94% and 1.45569 min-1, respectively, and the NIF concentration = 5 mg/L, pH = 7, the H2O2 dose = 0.52 mmol/L, T = 20 ℃ and the reaction time = 5 min. The ·OH was the primary key reactive oxygen species (ROS) and ·O2- was the secondary key ROS. There were 11 intermediate products (P345, P329, P329-2, P315, P301, P274, P271, P241, P200, P181 and P158) and 2 degradation pathways (dehydrogenation of NIF → P345 → P274 and dehydration of NIF → P329 → P315).


Introduction
Water pollution is a major environmental problem the world is facing today, mainly due to modernization [1]. The removal of toxic organic pollutants discharged from the ever-increasing number of industries is a major environmental goal [2,3]. Nifedipine (NIF, Fig 1), 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, belongs to the dihydropyridine class of calcium channel antagonists and is one of the most useful pharmaceuticals for the treatment of hypertension, angina pectoris and other cardiovascular a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 disorders [4,5]. As a large portion of each administered dose is excreted from medical applications and the pharmaceutical industry, and a substantial amount of NIF is released to the environment [6]. It has been demonstrated that NIF residues in the environment can result in the evolution of novel antibiotic-resistant bacteria that ultimately pose a threat to the aquatic ecosystem and human health through human organ lesions and increased bacterial resistance [7,8]. Hence, the efficient removal of NIF from water is significant and essential to reducing environmental and ecological risks. The removal of antibiotics from aqueous solutions has been widely researched, including removal by physical methods, chemical methods and biological methods [9][10][11][12]. Adsorption and advanced oxidation processes (AOPs, such as photocatalysis, Fenton, Fenton-like, photo-Fenton and catalytic ozonation) are the most promising wastewater treatment technologies for the removal of antibiotics from water environments and reduction of the resulting environmental risks because they are fast, efficient, low cost and convenient [13][14][15][16]. Many adsorbents have been employed for the eradication of antibiotics [17]. However, there are some drawbacks, such as incomplete removal, high energy requirements and the generation of toxic sludge and other waste products that entail further disposal [18]. Solar light-driven photocatalysis involves the photoinduced generation of holes (h + ) in the valence band (VB) and electrons (e -) in the conduction band (CB) via light absorption by a semiconductor (TiO 2 , ZnO and CdS). Sequential interfacial charge transfers release various reactive oxygen species (ROS), such as superoxide, peroxide, and hydroxyl radicals, which participate in the degradation of organic and inorganic pollutants [19][20][21][22]. However, the limitations of a wide bandgap, the rapid recombination rate of photogenerated electron-hole pairs, low solar light energy utilization efficiency, photocorrosion, and poor recyclability reduce the photocatalytic efficiency [23][24][25]. It is imperative to develop a novel Z-scheme system or heterojunction photocatalyst with broad photocatalytic applications [26,27]. However, limited research has focused on the removal of NIF from the water environment via AOPs. Therefore, it is important to study the removal of NIF via AOPs for the treatment of medical wastewater.
NIF is a known light-sensitive drug that degrades via intramolecular mechanisms to 4-(2-nitrophenyl) pyridine homolog (under UV light irradiation) and 4-(2-nitrosophenyl)-pyridine homolog (under daylight irradiation) [28]. Mojtaba Shamsipur et al. used a multivariate curve resolution method based on the combination of the Kubista approach and an iterative target transformation method by Gemperline to study the kinetics of NIF decomposition upon exposure to a 40 W lamp [29]. The results indicated that the photodecomposition kinetics of NIF are zero-order at the beginning of the reaction. However, when the reaction was more than 50% complete, the kinetics of the reaction changed to a first-order mechanism. The photo-degradation kinetics constants for the zero-order and first-order regions were (4.96 ±0.13) � 10 −9 M -1 s -1 and (6.22±0.10) � 10 −5 s -1 , respectively. This was the first study on the degradation of NIF, but the low degradation rate (65%) and kinetics limited the application of NIF removal via a photo-degradation system.
A novel method of UV light combined with hydrogen peroxide (UV/H 2 O 2 ) is highly efficient, fast, and has a strong oxidizing ability; these advantages are attributed to the synergistic ability of UV light and H 2 O 2 to generate ROS [30]. However, in UV/H 2 O 2 AOPs, other constituents in water matrices may significantly affect the removal of target contaminants by competitively interacting with photons and ROS. In our previous study, the degradation of norfloxacin by using UV/H 2 O 2 was investigated [31]. The degradation rate and apparent firstorder kinetics constant of norfloxacin via UV/H 2 O 2 were 98.8% and 0.22248 min -1 , respectively, and the norfloxacin concentration = 20 mg/L, the H 2 O 2 dose = 1.2 mmol/L, the pH = 7, T = 20˚C and the reaction time = 20 min. The kinetics were low, and the formation mechanism of ROS was controversial, but it provided a novel research direction for the degradation of NIF via a UV/H 2 O 2 system. Therefore, it should be noted that the degree of research to date on the degradation of NIF via UV/H 2 O 2 oxidation processes is insufficient to thoroughly understand the fundamentals of �OH generation, intermediate products and degradation pathways, which are important processes that must be considered in the design of wastewater treatment technology [32]. Furthermore, the effect of co-existing anions in the UV/H 2 O 2 system may significantly affect the removal of NIF by competitively quenching with ROS [33]. Thus, it is still challenging to design a UV/H 2 O 2 wastewater treatment technology with high efficiency.
On the one hand, the oxidizability of UV/H 2 O 2 AOPs and removal rate of NIF were enhanced due to the combination between UV and H 2 O 2 [30]. On the other hand, the anion (such as NO 3 -) was generated due to the degradation reaction between NIF and ROS. ) and monovalent anions (Cland NO 3 -) have been developed to model the impact of water constituents on the reaction kinetics. The aims of this study were to demonstrate the application of NIF degradation and to evaluate the performance and mechanism of UV/H 2 O 2 AOPs. The specific objectives were (1) to assess the effect of the H 2 O 2 dose, initial pH, and co-existing anions (SO

Chemicals
NIF was purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd. (Shanghai, China). Hydrogen peroxide (H 2 O 2 ), hydrochloric acid (HCl), sodium hydroxide (NaOH), sodium sulfate (Na 2 SO 4 ), sodium carbonate (Na 2 CO 3 ), sodium nitrate (NaNO 3 ) and sodium chloride (NaCl) were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Methyl alcohol (CH 3 OH) was purchased from Thermo Fisher Scientific (Shanghai, China). All chemicals and reagents used were of analytical grade or higher and directly used without further purification. All solutions were prepared with deionized water.

Experimental setup
The UV/H 2 O 2 degradation experiments (Fig 2) were conducted in deionized water with the addition of H 2 O 2 to the sample prior to 25 W UV light source exposure (254 nm). The initial NIF concentration was 5 mg/L, the temperature was 20˚C, the H 2 O 2 dose was 0-1.04 mmol/L and the pH was 4-10. To understand the effect of co-existing anions, different sources of SO 4 2-, CO 3 2-, Cland NO 3 -(from 5 to 50 mg/L) were added to the NIF degradation experiments to evaluate the removal rate and degradation kinetics.

Removal rate and degradation kinetics
The removal rate (η) of NIF under UV/H 2 O 2 was calculated using Eq 1 (Eq 1): where C 0 is the initial concentration of NIF and C t is the concentration of NIF at a certain degradation time, which was determined from the liquid chromatogram (S1 and S2 Figs). The degradation kinetics of NIF via UV/H 2 O 2 followed the apparent first-order kinetic law, and the apparent first-order kinetic constant (k ' app ) was described by Eq 2 (Eq 2): where t is the reaction time.

Organics analysis
NIF and its intermediate products in the UV/H 2 O 2 degradation reaction solutions were analyzed by an Agilent 1260 series liquid chromatogram mass spectrometry (LC-Q-TOF-MS) system (Agilent, USA) with a C18 column (100 mm × 2.1 mm, 3.5 mm). The wavelength was 237 nm according to ultraviolet and visible spectrophotometry (S1 Fig). The mobile phase was methyl alcohol and deionized water at 63:35 (v/v). The drying gas of N 2 was 8.0 mL/min, and the testing time was 30 min.

Electron spin resonance (ESR) measurements
ESR measurements were performed with a JES-FA200 electron spin resonance spectrometer and used to measure the hydroxide radical (�OH) and superoxide radical (�O 2 -) during the degradation of NIF under UV/H 2 O 2 using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as the spin trapping reagent.

Effect of H 2 O 2 dose
In general, the H 2 O 2 dose significantly affects the oxidative degradation of antibiotics by controlling the generation rate of ROS, and the effect of H 2 O 2 dose has been shown to have a dual nature. The specific degradation performance of NIF was enhanced by increasing the dose of H 2 O 2 when it was low; however, the degradation performance of NIF increased slowly, remained constant or decreased when the H 2 O 2 dose was high. As shown in Fig 3A and 3B and S1 Table,  The degradation kinetics constant noticeably increased as the H 2 O 2 dose increased and then remained constant at 1.5±0.1 min -1 . When the H 2 O 2 dose was < 0.52 mmol/L, the slope was 3.013 (min -1 )/(mmol/L), but it decreased to 0.266 (min -1 )/(mmol/L) when the H 2 O 2 dose was > 0.52 mmol/L; hence, the quasi-percolation threshold (QPT) of the H 2 O 2 dose was 0.378 mmol/L [34]. This trend was based on the generation and quenching of �OH described by (Eq 3) to (Eq 6) [35]:

Effect of initial pH
The pH is another key parameter of the UV/H 2 O 2 system. It significantly affects the oxidative degradation of antibiotics by transforming the protonation states and changing the redox potential at different pH values. As shown in Fig 4A and 4B and S2 Table,  The possible reasons were in accord with the redox potential, generation rate of ROS and reaction rate between ROS and NIF. The inhibiting effect of the basic solution was due to the quenching reaction between OHand �OH, which is shown in (Eq 7) to (Eq 11) [36]:

Effect of SO 4 2-
It is important to evaluate the effect of co-existing anions (such as SO 4 2-, CO 3

2-
, Cland NO 3 -) because the co-existing anions in wastewater impact the degradation capacity and the oxidation mechanism of ROS.
As shown in Fig 5A and 5B and S3 Table,

Effect of CO 3 2-
As shown in Fig 6A and 6B and S4 Table, Fig 7A and 7B and S5 Table,  The reaction mechanism between Cland �OH is shown in (Eq 23) to (Eq 27) [39]:

PLOS ONE
Highly efficient UV/H 2 O 2 technology for the removal of nifedipine antibiotics NO 3 and �OH is shown in (Eq 28) to (Eq 32) [40]: In summary, the effect of co-existing anions was as follows: The divalent anions (SO

Oxidation mechanism and degradation pathway of NIF via UV/H 2 O 2
In recent advances in UV/H 2 O 2 systems, the degradation of organic pollutants has been due to the generation of ROS, especially �OH and �O 2 -. The oxidation mechanism of NIF degradation via the UV/H 2 O 2 system was measured by ESR measurements, and the ESR spectra are shown in Fig 9A and 9B. The significant �OH signal (Fig 9A) showed four peaks at 321.8 mT (P A ), 323.3 mT (P B ), 324.8 mT (P C ) and 326.3 mT (P D ). The interspaces of P A -P B , P B -P C and P C -P D were constant of 1.5 mT, and the intensity ratio of P A , P B , P C and P D was 1:2:2:1 [41]. The significant �O 2 signal ( Fig 9B) showed four peaks at 322.1 mT (P' A ), 323.2 mT (P' B ), 324.4 mT (P' C ) and 325.8 mT (P D ). The interspaces of P' A -P' B , P' B -P' C and P' C -P' D were constant within the range of 1.0 mT from 1.5 mT, and the intensity ratio of P' A , P' B , P' C and P' D was 1:1:1:1 [42]. However, the intensity of the �OH signal was stronger than that of the �O 2 signal, which means that �OH was the primary key ROS and �O 2 was the secondary key ROS. The oxidation mechanism of NIF degradation via the UV/H 2 O 2 system is shown in (Eq 33) to (Eq 41) [43]. The generation of �OH mainly comes from the direct decomposition of H 2 O 2 (Eq 33), the generation of �O 2 mainly comes from the indirect reaction between oxygen gas (dissolved oxygen and H 2 O 2 decomposition) and electrons (Eqs 35 and 38), and NIF is degraded via the ROS (Eq 41) [44]. As shown in Fig 10A and 10B, the peak areas of all the observed products first increased and then decreased within 30 min. The peak areas of P345 and P274 at different reaction times are shown in Fig 10A, and the results indicated that the maximum peak area of P345 appeared at 5 min, the maximum peak area of P274 appeared at 20 min, and the peak intensity of P345 was stronger than that of P274.  Fig 11A [ 45,46]. The peak areas of P329 and P315 at different reaction times are shown in Fig 10B, and the results indicated that the maximum peak area of P329 appeared at 0.5 min, the maximum peak area of P315 appeared at 7 min, and the peak intensity of P329 was stronger than that of P315. , m/z = 181) [46]. P329 was present as an isomeride that was named P329-2 (m/z = 329). The intermediate products, P329-2, P301 (m/z = 301), P200 (m/z = 200)

Environmental significance
In this paper, fast, effective and low-cost UV/H 2 O 2 was used in the degradation of the antibiotic NIF, and this work contributed to the sustainable development of new methods for applications in hospital and aquaculture wastewater treatment for sustainable development, cleaner production and an environmentally friendly society, as shown in Table 1. The maximum degradation rate (99.94%), degradation kinetics constant (1.45569 min -1 ) and minimum degradation time (5 min) indicated that the UV/H 2 O 2 system is a promising AOP treatment for organic and medical wastewater. In addition, the cost of the UV/H 2 O 2 system was approximately $0.447 for 1 m 3 wastewater (S8 Table), which was lower than that of related systems (ranging from $0.53 to $0.85 for 1 m 3 wastewater) [47]. During the catalytic oxidation process, all the molecular mechanisms of ROS generation under the UV/H 2 O 2 system, the effects of coexisting anions in an actual water environment, the analysis of intermediate products and the degradation pathways were the basis of the efficient AOP design. Furthermore, intermediate products and the degradation pathways of pollutants should also be studied through theoretical simulation technologies such as density functional theory (DFT) and molecular dynamics (MD) [48].

Conclusions
The degradation rate and degradation kinetics of NIF first increased and then remained constant as the H 2 O 2 dose increased, and the quasi-percolation threshold was an H 2 O 2 dose of 0.378 mmol/L. The effect of the initial pH, divalent anions (SO 4 2-