Enhanced Naproxen Elimination in Water by Catalytic Ozonation Based on NiO Films

Round 1

Reviewer 1 Report

The studies aimed in application of NiO films as catalysts of naproxen degradation  by ozonation. The use of film instead of suspended metallic oxide is an innovative aspect of these studies.The NiO films  were prepared by CVD technique and characterized by adequate methods. The similar results were obtained  using NiO film and NiO suspension however NiO films can be easier reused.

Experimental studies were supported by mathematical modeling.

Author Response

Reviewer 1

• The studies aimed in application of NiO films as catalysts of naproxen degradation by ozonation. The use of film instead of suspended metallic oxide is an innovative aspect of these studies. The NiO films were prepared by CVD technique and characterized by adequate methods. The similar results were obtained using NiO film and NiO suspension however NiO films can be easier reused. Experimental studies were supported by mathematical modeling.

Answer. We appreciate your opinion on the positive aspects you have found in our manuscript.

Reviewer 2 Report

The paper "Enhanced naproxen elimination in water by catalytic ozonation based on NiO films" (Manuscript Number: catalysts-831571) is devoted to the catalytic ozonation of naproxen using nickel oxide films. Nickel oxide films prepared by CVD were characterized by X-ray diffraction, SEM, atomic force microscopy and X-ray photoelectron spectroscopy. The stability of the catalysts under ozonation conditions was studied. The authors compared conventional and catalytic ozonation with NiO films and NiO powder. Also, mathematical modelling of naproxen degradation by ozonation was performed.

However, the composition of naproxen ozonation products is not fully described. Only oxalic acid is mentioned as a decomposition product of naproxen.

As shown in Fig. 5a, naproxen degradation proceeds at the same rate without any catalyst and in the presence of NiO (film). This means that NiO(film) is not a catalyst.

The authors should explain, what the parameters k1, k2, and kc in Table 1 mean.

Row 4: “X-Ray Photoelectron spectrometry”. Correct: X-ray photoelectron spectroscopy.

Rows 206, 208: “Ni(acac)”. Correct: Ni(acac)2.

I think that this manuscript should be rejected.

Author Response

Reviewer 2

• The paper "Enhanced naproxen elimination in water by catalytic ozonation based on NiO films" (Manuscript Number: catalysts-831571) is devoted to the catalytic ozonation of naproxen using nickel oxide films. Nickel oxide films prepared by CVD were characterized by X-ray diffraction, SEM, atomic force microscopy and X-ray photoelectron spectroscopy. The stability of the catalysts under ozonation conditions was studied. The authors compared conventional and catalytic ozonation with NiO films and NiO powder. Also, mathematical modelling of naproxen degradation by ozonation was performed.

Answer. We appreciate your opinion on the positive aspects you have found in our manuscript.

• However, the composition of naproxen ozonation products is not fully described. Only oxalic acid is mentioned as a decomposition product of naproxen.

Answer. Thank you for the comment that coincides with some other comments (See editor’s questions number 4 and 5) regarding the oxalic acid was presented as the sole final product. The answers to those questions explain this byproduct´s dynamics deeply. We have detected several byproducts during ozonation with and without catalyst on the film by the ESI-Ms technique (Aguilar et al, 2019) and by HPLC. The first technique yields to detect four aromatic byproducts in samples after 5 min of reaction (Table 1). These ions m/z disappeared after 60 min of ozonation. Based on the HPLC analysis, it was possible to track the oxalic acid and a non-identified signal with 12.9 min of retention time (Figure 1) in the study with the C18 column (data not shown in the article). These both byproducts have dynamics of formation and degradation before the end of the reaction (their corresponding signals were not detected in HPLC analyses). So, the oxalic acid was the main detected final product at 60 minutes.

• As shown in Fig. 5a, naproxen degradation proceeds at the same rate without any catalyst and in the presence of NiO (film). This means that NiO(film) is not a catalyst.

Answer. We do not agree with this comment. There are several studies that have confirmed a similar comparative, where the catalyst effect was not detected in the degradation of initial compounds. However, the analysis of other parameters (TOC or byproducts formation/degradation) demonstrated the action of the catalyst on the ozonation. This behavior has been related to the fast reaction the ozone with the main compound, due to the selective attack of ozone with aromatic rings and unsaturated bonds of the molecule. Nevertheless, the byproducts generated of the first reaction are hardly decomposed by ozone but the presence of OH radicals may be decomposed them more efficiently. In consequence, the catalyst effect is more evident in the intermediates and finals products dynamics.  

• The authors should explain, what the parameters k₁, k₂, and kc in Table 1 mean.

Answer. The constants  and  are parameters used in the Super Twisting Algorithm. We have removed these constants from Table and we have included them in the text. The constant  is not corrected labeled. The symbol  was changed to  which is the pseudo-monomolecular reaction rate constant calculated with the method suggested in this study.

• Row 4: “X-Ray Photoelectron spectrometry”. Correct: X-ray photoelectron spectroscopy.

Answer. We have corrected the requested phrase in the text.

• Rows 206, 208: “Ni(acac)”. Correct: Ni(acac)₂.

Answer. We have corrected the requested phrase.

• I think that this manuscript should be rejected.

Answer. We have reorganized the manuscript accordingly your own suggestions and those provided by the associated editor as well as other reviewers. We hope that the reviewed version of our manuscript may deserve a better opinion from you. We believe that the findings attained in this study may contribute to identify the benefits of using catalyst over thin films in ozonation.

Reviewer 3 Report

The language of the manuscript needs a thorough polishing. There are instances of one-sentence paragraphs. In other places, sentences miss critical elements; “NiO(F) obtained by CVD technique presented a uniform gray color.” This sentence does not have a verb. Moreover, when discussing the results, the performance of CVD deposited NiO thin films should be compared with the catalytic activity of other oxides and preferably some atomistic insight to be provided as well. For instance, see the following reference: Assadi & Hanaor Applied Surface Science, 387, (2016), 682-689. In the introduction, add some recent methods of drug removal. For instance: Ultrasonics Sonochemistry, Vol 67, year 2020, page 105114.

Author Response

Reviewer 3

1. The language of the manuscript needs a thorough polishing. There are instances of one-sentence paragraphs. In other places, sentences miss critical elements; “NiO(F) obtained by CVD technique presented a uniform gray color.” This sentence does not have a verb.

Answer. We have made a detailed analysis of language usage in our manuscript. We have taken care or types and grammar mistakes. Also, we reorganized some paragraphs as you have suggested in your comment.

2. When discussing the results, the performance of CVD deposited NiO thin films should be compared with the catalytic activity of other oxides and preferably some atomistic insight to be provided as well. For instance, see the following reference: Assadi & Hanaor Applied Surface Science, 387, (2016), 682-689. In the introduction, add some recent methods of drug removal. For instance: Ultrasonics Sonochemistry, Vol 67, year 2020, page 105114.

Answer. We have checked the recommended references. We have included a couple of paragraphs in the reviewed version of our paper with the aim of comparing the proposed technique in this study with those included in the cited references.

Round 2

Reviewer 2 Report

Unfortunately, the composition of Naproxen degradation products is not described. Only oxalic acid is positioned as the final reaction product. However, based on the data in Figure 5b, the concentration of oxalic acid first increases, and then decreases during the reaction in the presence of NiO, but transformation of oxalic acid is not discussed. The authors listed by-products (rows 184-187), but the amounts of by-products are not given. The structure of Naproxen is not given. According to Figure 5b, if the amount of the reaction product is approximately the same after 60 min in the presence or absence of NiO, the use of NiO seems unreasonable. This manuscript can not be published in its present form.

Author Response

• Unfortunately, the composition of Naproxen degradation products is not described. Only oxalic acid is positioned as the final reaction product. However, based on the data in Figure 5b, the concentration of oxalic acid first increases, and then decreases during the reaction in the presence of NiO, but transformation of oxalic acid is not discussed.

Answer. We appreciate your opinion on the positive aspects you have found in our manuscript. Also, we tried to answer all your comments with the aim of presenting a better manuscript.

• The authors listed byproducts (rows 184-187), but the amounts of byproducts are not given.

Answer. Table A shows the four main molecules identified by Electrospray Ionization Mass Spectrometry (ESI-Ms-Ms). The NiO effect can be observed in oxalic acid profile over the time (Figure 5b). This organic acid is a recalcitrant compound to O₃-conv.

Table A.  Byproducts identified by the ESI-Ms-Ms analysis in NP degradation at 5 min of reaction.

217.09 m/z  1-(6-methoxynaphthalene-2-yl)ethylhydroperoxide	237.11 m/z 2-(3-(hydroxymethyl)-4-(2-methoxyethyl)phenyl)propanoic acid
177.66 m/z 2-(4-(2-hydroxyvinyl)phenyl)acetic acid	149.06 m/z 4-Methylphenylacetic acid

The concentrations of these components were not obtained because no standard solutions were acquired to prepare the corresponding reference curve. We detected these components in the ESI-MS which only gave the molecule identification but not the amount of them.

1. a) 1-(6-methoxynaphthalene-2-yl)ethylhydroperoxide,
2. b) 2-(3-(hydroxymethyl)-4-(2-methoxyethyl)phenyl)propanoic acid
3. c) 2-(4-(2-hydroxyvinyl)phenyl)acetic acid
4. d) 4-Methylphenylacetic acid

The listed compounds have a two-stage temporal evolution (accumulation and degradation) as shown in the following figure showing the chromatographic area in the HPLC analysis. This tendency confirms that all these intermediate compounds are close to be eliminated within the time window of the ozonation reaction (This fact is confirmed with the ESI-MS-MS analysis in samples taken after 60 min of ozonation). What is more important is that the decomposition of these compounds yields to the formation of organic acids (such as oxalic acid), aldehydes and carbon dioxide. All these compounds are considered as more biodegradable.

 

• The structure of Naproxen is not given.

Answer. We have included a new figure in the manuscript showing the chemical structure of naproxen. This figure corresponds to

• According to Figure 5b, if the amount of the reaction product is approximately the same after 60 min in the presence or absence of NiO, the use of NiO seems unreasonable.

Answer. We agree with the reviewer on the argument regarding the final amount of oxalic acid. However, you also have mentioned that oxalic acid is degraded along the reaction period. This fact is significant considering that degrading oxalic acid yields to produce aldehydes, organic acids of smaller molecular weight (such as formic acid) than oxalic acid and carbon dioxide. We have not introduced these compounds in the reaction pathway due to these compounds were not detected in the experiments considered in this study. Notice that oxalic acid removal implies the removal or total organic carbon from the reaction system. Moreover, the analysis of the averaged oxidation state of the carbon atoms (AOSC, equation 1) showed the values of 2.86 and 3.68 for the conventional and catalytic ozonation with NiO in powder, respectively, in samples taken at 60 min (Aguilar et al, 2019). The highest value of O₃-NiO(S) demonstrated a bigger oxidation stage for the byproducts in comparison with conventional ozonation. These facts confirm the catalytic effect.AOSC= 4 * 1.5(COT/TOC)

COT = Chemical oxygen demand

TOC = Total organic carbon

The AOSC results are in the interval of +4 to -4 (examples of carbon dioxide and methane AOSC values, respectively).

• This manuscript cannot be published in its present form.

Answer. We appreciate your opinion on the positive aspects you have found in our manuscript as well as on the negative issues. We have considered all those negative issues and we have tried to remove our fouls and mistakes. We hope that the modified manuscript will deserve a better opinion from you.

 

 

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors have carefully revised the paper accordingly and it's acceptable in the current format.

Author Response

1. The authors have carefully revised the paper accordingly and it's acceptable in the current format.

Answer. We have made a detailed analysis of language usage in our manuscript. We have taken care or types and grammar mistakes. Also, we reorganized some paragraphs as you have suggested in your comment.

Round 3

Reviewer 2 Report

I have two major concerns regarding this submission that should be addressed before further consideration is given. Firstly, the composition and amount of ozonation products have not been determined with the exception of oxalic acid. In turn, as can be seen from Figure 6b, oxalic acid is not the final reaction product and undergoes further transformation. The structures of the reaction by-products (rows 185-188) cannot be determined from MS-ESI data. Analysis by NMR spectroscopy is required.

Secondly, the role of NiO in the ozonation process is unclear. As shown in Figure 6a, the rate of degradation of naproxen is approximately the same in the presence of nickel oxide and without it. In the first three minutes of the reaction (see Fig. 6b), the content of oxalic acid in the reaction mixture is significantly higher in the presence of NiO than without it. The accumulation of oxalic acid in the first minutes of the reaction can be associated with the suppression of further conversion of oxalic acid by NiO. When ozonation is carried out for more than 10 minutes, the amount of oxalic acid is approximately the same in the presence and absence of NiO. I am not sure that NiO is a catalyst of naproxen ozonation.

The following points should be addressed:

1. Figure 1: The (S)-isomer should be drawn.
2. Row 183: “ESI-mass-mass (ESI-Ms-Ms) spectroscopy” should be “ESI-mass-mass (ESI-Ms-Ms) spectrometry”.

Author Response

Friday, July 19, 2020

Prof. Dr. Keith Hohn

Miami University

Editor-in-Chief Catalysts

Please find enclosed the corrected manuscript, “Enhanced naproxen elimination in water by catalytic ozonation based on NiO films by Claudia M. Aguilar-Melo, Julia L. Rodríguez, Isaac Chairez, Ivan Salgado, J. A. Andraca Adame, J. A. Galaviz-Perez, Jorge Vazquez-Arenas and Tatiana Poznyak, which we would like to re-submit as a Full-Length Article in Catalysts journal. We have addressed all the comments, queries and suggestions given by the reviewers and we have included the following main corrections:

• We have included several relevant details of the byproduct's dynamics obtained during the conventional and catalytic ozonation of NP
• We have added the explanation about the oxalic acid dynamics for the conventional and catalytic ozonation

Please address all correspondence to:

Dr. Jorge Isaac Chairez Oria.

Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional

E-Mail: [email protected]; [email protected]

We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with its submission to Catalysts journal. We look forward to hearing from you at your earliest convenience.

Sincerely yours

The authors

Reviewer 2

• I have two major concerns regarding this submission that should be addressed before further consideration is given. Firstly, the composition and amount of ozonation products have not been determined with the exception of oxalic acid. In turn, as can be seen from Figure 6b, oxalic acid is not the final reaction product and undergoes further transformation. The structures of the reaction by-products (rows 185-188) cannot be determined from MS-ESI data. Analysis by NMR spectroscopy is required.

 As the reviewer has pointed out, oxalic acid is not the final product of naproxen degradation. The final product of all advanced oxidation processes is carbon dioxide (mineralization). However, we included oxalic acid as an indicator of the oxidation effectiveness endorsed by ozonation (conventional and catalytic with suspended or supported NiO). Indeed, this acid is a recalcitrant molecule to the ozonation, which defines the significant importance of this byproduct as has been pointed out in diverse studies. In this study, oxalic acid concentrations after 60 minutes do not show significant difference between catalytic systems (film and powder) and conventional ozonation (Figure 6b).  The oxalic acid concentrations have different values during the first 10 minutes of reaction. Such changes seem to indicate that two different phenomena rule the ozonation kinetic with and without the catalyst. In the catalytic systems, there is the formation and subsequent decomposition of oxalic acid; while, in conventional ozonation only accumulation of the byproduct is detected. Such differences of oxalic acid concentrations, the analysis of byproducts concentrations (using Uv-vis spectroscopy, HPLC and ESI-Ms techniques) and the variations of TOC demonstrated the catalytic activity of NiO (films and powder) in ozonation of naproxen.

In a previous work of these authors (Aguilar et al. 2019), we proposed a feasible reaction pathway (Figure 1) to explain the naproxen degradation by conventional and catalytic ozonation. In this pathway, the final products were formic acid and CO₂. In the case of ozonation with NiO films as catalyst, the mineralization was demonstrated using the TOC removal results.

Figure 1. Reaction pathway for the naproxen ozonation with and without the catalyst (NiO) as presented by Aguilar et al., 2019.

The byproducts molecules proposed in the reaction pathway presented in Figure 1 were obtained by the analysis of the pattern fragmentation of ions m/z. Such patterns were obtained by the spectra acquired in the negative ion scan mode using a Bruker MICROTOF-Q II 10392. The analysis was carried out by direct injection in the ESI-TOF-MS system. The fragments were analysed by a Bruker Compass Data Analysis Software Version 4.0 (Bruker Daltonics). The widely accepted accuracy threshold for confirmation of elemental compositions was established at 5 ppm. The validation parameter is shown in Table 1 (Aguilar et al., 2019).

Table 1. Ions m/z proposed ESI-Ms-Ms analysis in the samples of naproxen degradation

 

We believe that byproducts study based on NMR may give some additional information to the one presented in this study; however, such information won't change the general conclusions attained in the present study. Notice also that the use of ESI- Ms technique has been employed in several studies to propose the byproducts distribution in ozonation reaction systems. Arany et al (2013) studied the naproxen degradation proposing 3 structures which were confirmed by HPLC-Ms with m/z of 218, 184 and 200. The structure of 218 m/z ion agrees with the molecule proposed in our work (Figure 2). Jallouli et al (2016) analysed the naproxen degradation by photocatalysis using UHPLC-DAD-Ms method as the main technique to characterize the byproducts distribution. In this work, five intermediaries were proposed, four of that with two aromatics rings (Figure 3). The naproxen ozonation byproducts identification by HPLC-Ms, GC-Ms and ESI-Ms-Ms techniques have been presented as complementary analytical methods to study ozonation efficiency even in the case of complex mixtures of compounds like urine (Aresta et al., 2006) or bioprocess effluents (Quintana et al., 2005). These results validate the strategy used in this study.

• Aguilar, C.M.; Chairez, I.; Rodríguez, J.L.; Tiznado, H.; Santillán, R.; Arrieta, D.; Poznyak, T. (2019) Inhibition effect of ethanol in naproxen degradation by catalytic ozonation with NiO. RSC Advance. 9: 14822–14833.
• Arany E., Szabó R.K., Apáti L., Alapi T., Ilisz I., Mazellier P., Dombi A., Gajda-Schrantz K. (2013) Degradation of naproxen by UV, VUV photolysis and their combination. Journal of Hazardous Materials. 262: 151–157
• Aresta, A., Carbonara, T., Palmisano, F., Zambonin, C. (2006) Profiling urinary metabolites of naproxen by liquid chromatography-electrospray mass spectrometry. Journal of pharmaceutical and biomedical analysis. 41: 1312-6
• Jallouli N, Elghniji K, Hentati O, Ribeiro AR, Silva AM, Ksibi M. (2016) UV and solar photo-degradation of naproxen: TiO2 catalyst effect, reaction kinetics, products identification and toxicity assessment. Journal of Hazardous Materials. DOI: 10.1016/j.jhazmat.2015.10.045
• Quintana J. B., Weiss S., Reemtsma T. (2005) Pathways and metabolites of microbial degradation of selected acidic pharmaceutical and their occurrence in municipal wastewater treated by a membrane bioreactor. Water Research. 39 (12): 2654-2664
• Secondly, the role of NiO in the ozonation process is unclear. As shown in Figure 6a, the rate of degradation of naproxen is approximately the same in the presence of nickel oxide and without it. In the first three minutes of the reaction (see Fig. 6b), the content of oxalic acid in the reaction mixture is significantly higher in the presence of NiO than without it. The accumulation of oxalic acid in the first minutes of the reaction can be associated with the suppression of further conversion of oxalic acid by NiO. When ozonation is carried out for more than 10 minutes, the amount of oxalic acid is approximately the same in the presence and absence of NiO. I am not sure that NiO is a catalyst of naproxen ozonation.

The reviewer is correct regarding that naproxen degradation rate is the same for conventional and catalytic systems. This result has been evidenced by different authors who have published similar results in the elimination of the main product. Ikhlaq et al (2018) confirmed that catalytic ozonation of paracetamol with zeolite as catalyst produced similar reaction rates with and without catalysts if the initial pH was fixed to 3 and 9.

An additional work (Alvárez et al; 2009) that shows a similar behavior to the reported in our work described the removal of gallic acid by catalytic ozonation with granular activated carbon. In this case, the gallic acid elimination profiles did not show differences during the treatment (20 min). However, the TOC removal after 20 min was close to 30% and 65% for conventional and catalytic ozone, respectively.

In our work, the catalytic effect of NiO as powder and films were demonstrated with the increase of TOC removal (10 and 22% for films and powder NiO, respectively; in comparison with conventional ozonation). Moreover, in our previous work regarding naproxen ozonation, the catalytic effect of NiO (powder) and the corresponding production of OH radicals were demonstrated using TBA as radical scavenger and the analysis of oxidation states of carbon atoms (AOSC). The AOSC analysis of samples after 60 min of the catalytic reaction showed the highest oxidation state of molecules in each collected sample, which indicates the accumulation of organic acid, aldehydes and eventually CO₂ (Aguilar et al, 2019). These results difficult the possibility of suppressing oxalic acid degradation by the presence of NiO, due to the high constant reaction of this organic acid with OH radicals and even the possibility to form complex (NiO – oxalic acid) as a mechanism of degradation. Oxalic acid in the reaction produced by conventional ozonation never growth above 4 mg/L. However, the presence of NiO accumulated oxalic acid beyond 10 mg/L at the minute 1 and it decreases down to 4 mg/l at 60 min. This means that oxalic acid is also decomposed during the period of ozonation reaction in presence of NiO. This characteristic is hardly observed in conventional ozonation.

• Alvárez P.M., Beltrán F.J., Masa F.J., Pocostales J.P. (2009) A comparison between catalytic ozonation and activated carbon adsorption/ozone-regeneration processes for wastewater treatment. Applied Catalysis B: Environmental. 92(3):393 – 400
• Ikhlaq A., Waheed S., Khurram S., Kazmi M. (2018) Catalytic ozonation of paracetamol on zeolite A: Non-radical mechanism. Catalysis Communications. 112: 15 – 20
• Figure 1: The (S)-isomer should be drawn.

We have included the S-isomer. This figure corresponds to:

• Row 183: “ESI-mass-mass (ESI-Ms-Ms) spectroscopy” should be “ESI-mass-mass (ESI-Ms-Ms) spectrometry”.

We have changed phrase “ESI-mass-mass (ESI-Ms-Ms) spectroscopy” to “ESI-mass-mass (ESI-Ms-Ms) spectrometry”.

Author Response File: Author Response.pdf