The discharge of pharmaceutically active compounds and their metabolites into wastewater and their subsequent release into the aquatic environment is of great concern. These constituents pose potential risks to the environment and living organisms especially since conventional wastewater--treatment processes do not adequately remove them or inadvertently transfer them from one phase to another in sludge, biosolids, and manure [1–3]. Pharmaceuticals detected in wastewater before and after treatment are released from industry, hospitals, and domestic sewage. Novel wastewater-treatment methods seek to remove these recalcitrant, bio--accumulative, and toxic substances while retaining economic feasibility and efficiency. Additionally, sensitive methods to detect these compounds even at low concentrations are a prerequisite [4–6].
Hydroxychloroquine (HCQ), a synthetic quinoline derivative, is an antimalarial with anti-inflammatory properties used in oncology, rheumatology, dermatology, and more recently proposed in the therapy of severe acute respiratory syndrome coro-navirus 2 (
HCQ is susceptible to photochemical decomposition reactions in the natural environment, with humic acids acting as photosensitizers and filters in the photodegradation by promoting the formation of reactive hydroxyl radicals [7, 8]. Additionally, catalytic processes using titanium oxide containing beta bismuth oxide (P-Bi2O3) [12], sono-catalytic activity using the MoS2/CNTs nanocomposite [13], electrochemical oxidation using boron--doped diamond electrodes [14, 15], Ti3GeC2 with 0.15 mmol·L-1 of peroxydisulfate (PDS) under ul-trasound irradiation [16], and the ZnO-CP catalyst [17] are popular alternatives. Adsorbents, such as: living microalgae [18], H3PO4 activated
Methods for the removal of hydroxyquinine from aqueous solutions
Method | Conditions | Efficiency | Ref. |
---|---|---|---|
Photochemical decomposition | pH 3–10 | Half-lives of 5.5 min (pH3) to 23.1 h (pH4) Hydrolytic degradation <5% | [7, 8] |
Adsorbents | |||
Living microalgae | HCQ 20 mg·L-1, pH 9.9, 45 min, 300 rpm stirring speed microalgae loading of 100 mg·L-1 | 92.10 ± 1.25% maximum biosorption capacity is 339.02 mg·g-1 | [18] |
H3PO4-activated |
Adsorbent dose (0.025–1 g·L-1), pH (4–11) contact time (0–240 min) HCQ (10–50 mg·L-1) | 98.9% (qmax = 353.58 mg·g-1) surface area (1088.806 m2·g-1) | [19] |
Natural zeolite CP | pH 2–7.5 298 K, 303 K, and 308 K | 7 mg·g-1 7 cycles reuse | [20] |
Algerian kaolin | 0.05–0.15 g·L-1 sorbent, and pH of 3–7 5–50 mg·L-1 HCQ | Capacity of 51 mg·g-1 0.15 g·L-1 of kaolin, 5 mg·L-1 as HCQ initial concentration, and pH 7 are optimal | [21] |
Catalysis | |||
ZnO-CP catalyst | 2 g·L-1 15% ZnO-CP pH = 7.5 UV-A radiation, 10 mg·L-1 HCQ, 180 min | 96% | [17] |
Modified titanium oxide using beta-bismuth oxide TiO2/ß-Bi2O3 | 120 min, pH 3–11 10 mg·L-1 HCQ, 0.1 g·L-1 catalyst, 0.1 mg·L-1 H2O2 | 91.8% 6 cycles >70% degradation | [12] |
MoS2/CNTs nanocomposite | MoS2/CNTs 10:1 ratio loading of 0.1 g·L-1 pH of 8.7, HCQ-20 mg·L-1 120 min | 70% Lower band gap energy (1.2 eV), higher specific surface area (30.6 m2·g-1) | [13] |
Ti3GeC2 with peroxydisulfate | 20 mg·L-1 HCQ 0.2 g·L-1 Ti3GeC2, 0.15 mmol·L-1 PDS, ultrasound irradiation 80 min | 60.42% Dependent on catalyst dosage (0.1–0.2 g·L-1) | [16] |
Advanced oxidation processess | |||
Electrochemical oxidation | BDD anodes, HCQ 36–250 mg·L-1, |
100% | [14] |
Electrochemical oxidation | BDD electrode 15 mA·cm-2, 30 mA·cm-2, and 45 mA·cm-2 | 100% COD (68%, 71%, and 84%) | [15] |
Fe(0)/ |
98.95% | [21] | |
Gamma irradiation | 100 ppm HCQ A dose rate of 26.31 Gy·min-1 pH = 6.2 | 98.5% TOC removal (8 kGy) complete mineralization | [22] |
Gamma irradiation | 20 ppm HCQ, 1 kGy dose 4.2 kGy1 | 100% | [23] |
BDD, boron doped diamond; CNTs, carbon nanotubes; COD, chemical oxygen demand; CP, clinoptilolite; HCQ, hydroxy-chloroquine; TOC, total organic carbon; UV-A, ultraviolet A.
HCQ sulfate powder (MW = 433.95, 99%), NaOH (99%), potassium dichromate (99%), silver nitrate (99%), perchloric acid (95%), and H2SO4 (98%) were purchased from Sigma-Aldrich (Merck-Germany). Fresh solutions of HCQ and other solutions were prepared in distilled water from the Thermo Fisher distillation unit from Merck (Germany).
A Jasco V670 spectrophotometer (Poland) was used for the detection of HCQ (>1 mg·L-1) with the maximum absorption at 343 nm. Nanocolor test kits from Mercherey Nagel (Germany) purchased from Aqua Lab (Poland) tests were used for the photometric determination of total Kjeldhal nitrogen (1.0–16 mg·L-1), total nitrogen (0.5–50 mg·L-1), nitrate
Irradiation was performed using a batch system with aqueous solutions containing varying concentrations of HCQ in distilled water. Irradiation was performed on the ILU6 accelerator at the energy of 1.65 MeV, 2 Hz, and 50 mA. A solution of 0.0005 M potassium dichromate mixed with silver nitrate solution in 0.1 M perchloric acid was used for dosimetry. Additionally, alanine dosimeters were used to determine the applied radiation doses delivered to the aqueous system [24–27]. Low-density polyethylene (LDPE) sleeve bags were filled with 35 mL of HCQ solution and irradiated under the accelerator window. Different initial pH values were selected to study the effect of pH on the degradation efficiency of solutions of HCQ under electron beam processing. The pH values were attained by adjusting the pH of the solution with 0.1 M NaOH and 0.1 M sulfuric acid.
The interaction of radiation with water molecules leads to ionization and excitation events that eventually through physical-chemical and chemical reactions lead to the formation of reactive radical species among other molecules with corresponding radiation chemical yields (G-values in parenthesis) in molecules/100 eV.
The hydroxyl radical is a strongly oxidizing species synonymous with the hydroxy radicals generated in advanced oxidation processes. Additionally, reducing species such as the hydrated electron and hydrogen atom are simultaneously produced in the radiolysis of water. These highly reactive species in the natural aqueous environment interact with HCQ and control its stability, degradation, and fate [7, 8]. Alternatively, these radicals can be generated in wastewater-treatment processes to propagate the destruction and removal of HCQ from wastewater. Using electron beam processing, the reactions of hydrated electrons
Dégradation of 2.88 × 10-4 M of hydroxychloroquine under electron beam treatment. (a) UV-VIS absorption spectrum of HCQ solution with an initial concentration of 2.88 × 10—4 M was observed at 343 nm at doses ranging from 0 kGy to 7 kGy. (b) The removal efficiency of 2.88 × 10-4 M HCQ solution under EB irradiation.
The overall decrease in HCQ concentration was 82% of the initial concentration (Fig. 1b). This observation is consistent with observations in pulse radiolysis where the concentrations of the reactive species increase with increasing dose, therefore, increasing their contribution to the degradation of HCQ with increasing dose [28, 29]. Rath
Reaction rates of aminoquinoline derivatives with hydroxyl radical and hydrated electrons
Reactive spp | Hydroxychloroquine [30] | Chloroquine [31] | Amodiaquine [32] |
•OH | 9.5 × 109 M-1·s-1 | 7.3 × 109 M-1·s-1 | 9.0 × 109 M-1·s-1 |
2.0 × 109 M-1·s-1 | 4.8 × 1010 M-1·s-1 | 1.6 × 1010 M-1·s-1 |
The corresponding reactions for these reductive and oxidative reactions with HCQ are provided in Eq. (1) and Eq. (2) [33].
The reaction between HCQ and •OH radicals (Eq. (2)) forms transient intermediate species having two absorptions at 330–340 nm (Fig. 1a). Rath
The influence of initial pollutant concentration on the radiolytic degradation efficiency of HCQ was studied. The increase in pollutant concentration negatively affected the degradation efficiency. The degradation efficiency decreased with increasing HCQ concentration as shown in Fig. 2a. Similar results have been obtained in the radiolytic decomposition of other organic compounds as well as the degradation of HCQ under gamma irradiation [22].
Degradation of different concentrations of hydroxychloroquine solutions under EB irradiation. (a) Variation in the removal efficiency with increasing HCQ concentration. (b) Variation of reaction rate
From the experimental results and under normal conditions, it was possible to achieve 90% degradation of 25 mg·L-1 HCQ and about 76% for 125 mg·L-1 for a maximum dose of 7 kGy. Most radiolytic decompositions of the target pollutants can be described by the pseudo-first-order kinetic reaction [22, 23].
where
Rate constant
Concentation (mg·L-1) | ||
75 | 1.1287 | 0.9974 |
100 | 1.0706 | 0.9887 |
125 | 0.8980 | 0.9443 |
The solvent pH influences the proportion of the different radicals generated during the radiolysis of the water. Under alkaline conditions, •OH readily reacts with OH-to generate O•-, which is a less powerful oxidant thereby reducing the concentration of •OH and the degradation efficiency (Eq. (7)) [35–37], However, more hydrated electrons
Different pH values were chosen for the start of the irradiation process. From Fig. 3a, >80% of the initial HCQ concentration was removed at a maximum dose of 7 kGy for pH between 2 and 10. However, at a pH of 12, the removal efficiency declined (-60%). In experiments utilizing electrochemical oxidation with boron-doped diamond anodes, about 60% removal efficiencies were observed at similar pH ranges [14]. Similar to these studies, an acidic pH of 2 favored the decomposition of HCQ but de-composition reduced with increasing pH. However, for the electron beam process, the degradation efficiency was also better at pH >7. Additionally, for pH between 4 and 8, the pH was observed to decrease with increasing dose and stabilized at a pH of about 3.5 (Fig. 3b). Similar observations were made under gamma irradiation at pH between 4 and 8 [23]. In the present study, pH of 2 and 8 gave the highest removal efficiency ≥84%.
The effect of pH on the removal of 2.88 × 10-4 M of hydroxychloroquine. (a) Removal efficiency under different initial pH under electron beam treatment. (b) The changes in pH during electron beam irradiation with different initial pH.
The solution at an initial pH of 2 was at a stable value throughout the irradiation process. The solutions at initial pH of 10 and 12 dropped to values of 6.5 and 11.5, respectively. The decrease in the pH alludes to the formation of acidic or less basic intermediates during the degradation of HCQ. Additionally, the pH influences the molecular properties of HCQ, which has three functional groups with pKa values of <4.0, 8.3, and 9.7. At acid and neutral conditions, two of the functional groups exist in protonated forms [30, 38]. This may facilitate the rupture of C–N bonds by •OH radicals attack and lead to the release of the branched group [14]. HCQ is a basic substance, completely protonated at acidic pH values, as H2HCQ2+. At neutral values of pH, two protonated forms of HCQ are formed: H2HCQ2+ and HHCQ+ [39]. Similarly, the degradation of HCQ was high at pH values of 8 and 10. In alkaline media, the ratio between the protonated form HHCQ+:HCQ is 1:6, meaning that the HCQ is mostly deprotonated. Higher degradation in alkaline solution indicates that deprotonation increases the electron density on HCQ and favors the electrophilic attack by reactive oxygen species, such as hydroxyl radicals. The quinoline ring is more susceptible to the attack of hydroxyl radicals at pH 9 than at pH 4 [7]. Regarding the half-life times (
The increasing concentration of solvated electrons at high pH leads to a decrease in the concentration of hydroxyl radicals so the redox reaction is extremely rapid. At pH = 6.2, all reactive species are free and are not involved in other reactions. Gamma radiolysis of 20 ppm HCQ at pH of 4, 6.8, and 9 showed an overlap in removal efficiency in acidic to neutral conditions [23]. A similar observation is made for pH between 4 and 7 under EB treatment (Fig. 3a). However, in basic conditions, the removal efficiency increased with dose. Under electrochemical oxidation, >60% of the initial HCQ concentration was eliminated for pH between 2 and 12 similar to what is reported in this work. However, the efficiency decreased with increasing pH to 12 [14]. The decrease in the removal efficiency at pH 12 could be attributed to reactions in Eq. (7). The pH of wastewater is a vital component before, during, and after treatment for the eventual discharge of wastewater.
The degradation byproducts discussed in this section are based on the degradation of 125 mg·L-1 of HCQ solution under electron beam irradiation at neutral pH.
The pH of the solution was observed to change from slightly acidic of pH 6.5 before irradiation to an acidic pH of 3.5 at the end of irradiation (Fig. 4). At the lower pH, degradation of HCQ was diminished according to Figs. 1 and 2. Similar changes in pH during the degradation of organic compounds have been attributed to the formation of lower molecular--weight carboxylic acids such as oxamic and oxalic acid, ketones, aldehydes, and ions [14, 41].
Changes in pH concentration during electron beam treatment of 2.88 × 10-4 M HCQ. The pH varied from slightly acidic before irradiation to acidic at the end of irradiation.
From Eq. (1), dissociative electron attachment is accompanied by the release of chloride ions (Cl-). There was a total Cl- ion release at 7 kGy (Fig. 5). Similar dechlorination has been reported while using gamma radiation [22]. This is synonymous with dissociative electron attachment, which is a common reaction of the hydrated electron with halogenated compounds. The evaluated rate constants for this reaction have been provided [33]. The chlorine group is presumed to be responsible for the toxicity of organic compounds. The dechlorination of HCQ treatment, therefore, implies a decrease in the toxicity of the aqueous solution. However, in the present study, toxicity assessment was not performed.
Release of the Cl- ion during the degradation of 2.88 × 10-4 M solution of HCQ under electron beam treatment.
Nitrogen-containing organic wastewater poses a challenge in wastewater treatment as it is repeatedly transformed in the nitrogen cycle and enters water and wastewater via agricultural, domestic, and manufacturing wastes. The nitrogen atom in the cyclic ring of quinolone increases the hydrophilicity, solubility, and low biodegradation, which increases the potential for the incidence of HCQ in water environments [7, 8]. Nitrogen in the form of organic nitrogen and ammonia in freshly polluted water are converted by a biochemical process into ammonium to be utilized as a nutrient by microorganisms in the treatment process. Under aerobic conditions, the organic nitrogen is converted into ammonia and then further oxidized into nitrite and eventually into nitrate. The total Kjeldahl nitrogen (TKN) monitors the degree of contamination of the discharged water. Figure 6a shows that about 75% of the nitrification was achieved during the electron beam radiolysis of a 2.88 × 10-4 M solution of HCQ at 7 kGy dose. A reduction in TKN with a simultaneous increase in
(a) Nitrification of organic bound nitrogen (HCQ[N]) with subsequent formation of
DO is the amount of oxygen dissolved in water and is available to living aquatic organisms indirectly inferring to water quality. The DO is consumed as organic matter decays. In high levels of organic pollution, biochemical oxygen demand (BOD), or COD, a large amount of DO is consumed through aerobic microorganisms to decompose the organic matter, which causes a reduction in the DO level. The DO during the radiolysis of 2.88 × 10-4 M of HCQ solution showed a slight decrease from 4.5 mg·L-1 to 3.8 mg·L-1 as shown in Fig. 7.
Changes in the dissolved oxygen concentration during electron beam irradiation of 2.88 × 10-4 M HCQ.
In addition to the DO, another important parameter is the oxygen demand. The complete mineralization of target pollutants is the main aim of wastewater treatment. However, most processes achieve minimal to partial mineralization. Mineralization can be evaluated using the oxygen demand, which determines the amount of organic pollution in water, waste loadings of treatment plants, and the efficiency of treatment processes. Industries that produce vaccines/antitoxins generate wastewater containing very high BOD, COD, total solids, colloidal solids, toxicity, and odor. Figure 8 shows the COD and TOC variation with increasing doses during electron beam treatment of a 2.88 × 10-4 M solution of HCQ. There was a slight decrease in the COD, but TOC remained fairly constant during the irradiation process. This is indicated by the transformation of the initial compound into other organic degradation products such as organic acids. These products are less susceptible to oxidation by initial water radiolysis products.
Variation in COD and TOC during electron beam degradation of 2.88 × 10-4 M HCQ aqueous solutions.
In studies on the radiolytic decomposition of HCQ under gamma irradiation, COD and TOC elimination were observed to increase with increasing applied dose [22]. The removal efficiency was >98.5% at doses up to 8 kGy. Higher dose rates, low pollutant concentration, and neutral pH facilitated mineralization. Similar TOC elimination efficiencies have been reported under electrochemical oxidation [14]. Electron beam treatment has comparatively higher dose rates than gamma irradiation but did not show higher TOC reduction. The slower removal efficiency can be attributed to the production of carboxylic acids and aliphatic chains that were more refractory than the initial HCQ.
In this study, HCQ was effectively decomposed with >80% of the initial concentration of a 2.88 × 10-4 M solution. From the results, dechlorination and nitrification were achieved at applied doses between 0.5 kGy and 7 kGy. However, from the results of TOC and COD, complete mineralization was not achieved, and it is surmised that the HCQ degraded into other organic compounds, i.e., carboxylic acids that are less susceptible to degradation under the study conditions [22]. Further oxidative decomposition of byproducts through hydroxyl radical attack leads to the production of carboxylic acids (among them oxamic and oxalic acids), which have been attributed to the decrease in pH during EB irradiation of aqueous solutions of HCQ. The carboxylic acids can be slowly oxidized and require the consumption of a high irradiation dose to be slowly mineralized into carbon dioxide and water [14]. The release of inorganic ions and nitrogen species predominantly in the form of Cl-,