Optimization of Binary Adsorption of Metronidazole and Sulfamethoxazole in Aqueous Solution Supported with DFT Calculations

Round 1

Reviewer 1 Report

processes-2284023 – Optimization of binary adsorption of metronidazole and sulfamethoxazole in aqueous solution supported with DFT calculations.

1- The introduction could be improved by referring to the following refs including 

https://doi.org/10.3390/molecules27227980

https://doi.org/10.3390/pr7110835

https://doi.org/10.1016/j.jcis.2020.08.065

which can offer help to compose a better writing for the introduction and retrieve useful information regarding this work as well.

2- Analysis of data/results and focus of aims should be further elevated.

I recommend this work for publication after minor revision

Author Response

Reviewer 1

I recommend this work for publication after minor revision:

• The introduction could be improved by referring to the following refs including. 

https://doi.org/10.3390/molecules27227980

https://doi.org/10.3390/pr7110835

https://doi.org/10.1016/j.jcis.2020.08.065

which can offer help to compose a better writing for the introduction and retrieve useful information regarding this work as well.

Authors' response: Introduction section has been improved. The articles mentioned above have been added to the test. The following paragraph have been included in the introduction section:

Line 41-46: Antibiotics are used in humans and animals, but the organisms cannot fully absorb them, and they are released into the environment in an active form [1] . Then, antibiotics can create an adverse effect on aquatic fauna as bioaccumulation, and consequently, getting into the food chain and then enter to the human body again [1]. Thus, the ingest of antibiotic residues can alter the human microbiome and promote emergence and selection for bacteria resistance residing in the body [4]

Line 49-51: This situation increases the possibility of creating a selection pressure on environmental microbiome, which can lead to the generation of antibiotic resistance reservoirs in the environment [4].

Line 67-85: This technology has been applied successfully to 30 different antibiotic compound elimination [1]. Several adsorbents have been used for the adoption of SMX and MNZ, such as clays, metal-organic frameworks, and activated carbon materials (AC). The last one is, the most useful due to its excellent physicochemical stability and high specific surface area (500-2000 m² g^-1) [2][3]. In this sense, Ariyanto et al., [3] studied the effect of pore structure and surface oxidation of a nanoporous carbon on the adsorption performance of MNZ, finding that the oxidized carbon material favored MNZ adsorption. In the case of SMX, Li et al., [1] have evaluated the adsorption of SMX on AC, finding a maximum adsorption capacity of 26.77 mg g^-1. On the other hand, in our research group, it has been carried out the single adsorption of MNZ and SMX on AC, finding that the adsorption process is dominated by π-π dispersive interactions [5][6].

 

 

Line 91-94: The results have been statistically analyzed to determine the best conditions for maximizing the removal of both pharmaceuticals as a function of the solution pH, temperature, and initial concentrations of both pharmaceuticals.

Bibliography:

1. Li, R.; Sun, W.; Xia, L.; Zia, U.; Sun, X.; Wang, Z.; Wang, Y.; Deng, X. Adsorption of Toxic Tetracycline, Thiamphenicol and Sulfamethoxazole by a Granular Activated Carbon (GAC) under Different Conditions. Molecules 2022, 27, doi:10.3390/molecules27227980.
2. Ahmed, I.; Adhikary, K.K.; Kim, K.; Ahn, W.S. Aqueous Adsorption of Sulfamethoxazole on an N-Doped Zeolite Beta-Templated Carbon. J Colloid Interface Sci 2021, 582, 467–477, doi:10.1016/j.jcis.2020.08.065.
3. Ariyanto, T.; Sarwendah, R.A.G.; Amimmal, Y.M.N.; Laksmana, W.T.; Prasetyo, I. Modifying Nanoporous Carbon through Hydrogen Peroxide Oxidation for Removal of Metronidazole Antibiotics from Simulated Wastewater. Processes 2019, 7, doi:10.3390/pr7110835.
4. Ben, Y.; Fu, C.; Hu, M.; Liu, L.; Wong, M.H.; Zheng, C. Human Health Risk Assessment of Antibiotic Resistance Associated with Antibiotic Residues in the Environment: A Review. Environ Res 2019, 169, 483–493.
5. Moral-Rodríguez, A.I.; Leyva-Ramos, R.; Ocampo-Pérez, R.; Mendoza-Barron, J.; Serratos-Alvarez, I.N.; Salazar-Rabago, J.J. Removal of Ronidazole and Sulfamethoxazole from Water Solutions by Adsorption on Granular Activated Carbon: Equilibrium and Intraparticle Diffusion Mechanisms. Adsorption 2016, 22, 89–103, doi:10.1007/s10450-016-9758-0.
6. Carrales-Alvarado, D.H.; Leyva-Ramos, R.; Martínez-Costa, J.I.; Ocampo-Pérez, R. Competitive Adsorption of Dimetridazole and Metronidazole Antibiotics on Carbon Materials from Aqueous Solution. Water Air Soil Pollut 2018, 229, doi:10.1007/s11270-018-3730-4.

 

2- Analysis of data/results and focus of aims should be further elevated

Authors response: Analysis of data have been improved adding a detail discussion. The following paragraph were added to the manuscript:

Line 206-210: In Figure 2, it can be observed that at equilibrium concentrations (Ce) lower than 0.15 mmol L^-1 the carbon surface showed a slightly better affinity by MNZ, however at higher concentrations at equilibrium SMX adsorbed much better than MNZ. As an example, at an equilibrium concentration of 0.6 mmol L^-1, the adsorption capacity to-wards SMX and MNZ were 1.3 and 1.04 mmol g^-1.

Line 225-228: The discussion about this behavior during adsorption will be supported by the computational results presented in section 3.2, associated with the different stablished inter-actions between the antibiotics and the surface of GAC F400.

 

Line 237-240: The maximum adsorption capacities from Langmuir model were1.61 mmol g^-1 and 1.10 mmol g^-1 for SMX and MNZ, respectively. These values are similar to those obtained in the literature using activated carbon.

Line 237-240: Considering the values of the regression coefficient (R2) and the average deviation percentage (%D) of each model, the Prausnitz and Langmuir isotherm models (Figure 2) describe the experimental data adequately. The maximum adsorption capacities estimated from the Langmuir model were 1.61 mmol g^-1 and 1.10 mmol g^-1 for SMX and MNZ, respectively. These values are similar to those obtained in the literature using activated carbon.

Line 256-269: From the values of F and p reported in Table S4, the [SMX] term is the factor most ifluencing the q_SMX given that it shows the largest F value and the smallest p value. Finally, the model showed a p value smaller < 0.0001 with no significant lack of fit, which indicates that the model can describe the change of qSMX as a function of the factors studied.

The final model to describe the q_SMX, after a depuration process and considering the factors hierarchy, is represented with the following equation.

A similar analysis was performed to identify the significant terms during the adsorption of MNZ, supported by the ANOVA analysis showed in Table S5. For this case, the statistically significant factors (Table S5) were the pH, [SMX], [MNZ], pH², and the interaction be-tween pH and [MNZ]. The mathematical model to describe the q_MNZ, is given by the following equation.

Line 277-281: Fig. S2a-b shows the correlation between the experimental data for q_SMX and q_MNZ, respectively with the prediction of equations 5 and 6, where a random distribution can be observed over the 45° line for both cases. Furthermore, the values of R² for the mathematical models were 0.9658 and 0.9426, which indicates that Eqs. (5) and (6) can predict the response successfully.

Line 292-297: The results reveal that q_MNZ is drastically dependent on the initial MNZ concentration, increasing favorably as the concentration of MNZ increases. As an example, at pH 6 and an initial SMX concentration of 0.2 mmol L^-1 the values of q_MNZ were 0.6, 0.4, and 0.2 mmol g^-1, at initial MNZ concentration of 0.03, 0.16 and 0.30 mmol L^-1, respectively. In Figure 3a, it can also be seen that pH has a significant influence on q_MNZ mainly at initial concentrations greater than 0.16 regardless of the presence of SMX.

Line 309-312: Finally, during the adsorption of MNZ in the presence of SMX, the temperature was not a significant parameter. Carrales-Alvarado et al. [22] showed that during single adsorption of MNZ on activated carbon, the adsorption capacity at 10, 20 and 35 °C was not affected by temperature.

Line 318-322: The highest adsorption capacity of SMX is found at low pH (pH= 2) regardless of the presence of MNX, where SMX is neutral and positive in a 1:1 ratio. At this pH, there is a protonated amido group that generates a positive charge in the molecule, but it seems that is not a positive charge strong enough to have significant repulsive interactions with GAC F400.

Line 323-328: In Figure 3b it can be seen that the presence of MNZ in the binary process does not affect the adsorption of SMX regardless of solution pH. However, at [MNZ] concentrations of 0.16 and 0.30 mmol L^-1 at pH 2, the presence of MNZ significantly affects the adsorption capacity of SMX. As an example, at [SMX] of 0.16 mmol L^-1 in the absent of MNZ, the adsorption capacity is qSMX=0.2 mmol g^-1, but in the presence of MNZ (0.3 mmol L^-1) the adsorption capacity is duplicated

Line 338-344: Thus, SMX adsorption increased because MNZ molecules provides order to adsorption process. We propose that MNZ is adsorbed between SMX molecules this action generates a stable adsorption process. π-π stacking interactions between SMX and MNZ contribute to more stable stacking process. Since SMX and MNZ electron density in their aromatic rings are different this generates stronger π-π interactions. MNZ rings is deactivated by nitro group and SMX is an activated ring by amino group. This difference in electron density favored stacking among different rings.

 

Line 362-364: This can see in Table S6, from ANOVA, the interaction of [SMX] and pH is significant because, in this pH range, the adsorption capacity of SMX is larger than de MNZ.

Line: 369-372: Furthermore, the interaction between [MNZ] and pH in the model design is not significant, therefore pH does not affect the adsorption, Moreover, as it showed in Figure 1a, it could see that the speciation of MNZ does not change in a wide range of pH.

Reviewer 2 Report

The manuscript presents the innovation of using two emerging contaminants in a quantitative adsorption analysis. However, the activated carbon used is a commercial material, marketed for this purpose. Furthermore, the removal efficiency (%) is not explored in the text, leaving many doubts as to its real application. I believe that the manuscript may be suggested for publication if some corrections are made (listed below).

In general, the manuscript needs to be revised for its spelling and structure;

Please replace the word "elimination" with a more appropriate word. Line 14;

Please rearrange the references. line 54;

Do the authors believe that the adsorbent should be able to retain all the compounds of a real effluent? (line 57-59) Please review this statement, if indeed it is the opinion of the authors, explore this statement further. Since 100% removal efficiency of all compounds present is quite ambitious;

Please correct reference 19. Line 84. - Do not include the year in citations [x], review the entire manuscript;

Please add the full name of the abbreviations described in Table S1;

Granular activated carbon sounds extremely generic. Please replace the current AC nomenclature, stating that it is commercial carbon and, preferably, the raw material used in its synthesis;

Please correct the word "adsorbent" (line 113). Aliquots were taken from the mixtures;

Figure 1 is misplaced in the manuscript;

Please explain in the manuscript how the authors guarantee that the temperature of 40ºC did not interfere with the drug molecule;

There are two "Figure 2" in the text;

Where is equation 4 in the supplementary material? (line 18);

Table S2 is misplaced in the manuscript. It presents the values of dependent variables on the experimental design in the methodology.

Author Response

Reviewer 2

The manuscript presents the innovation of using two emerging contaminants in a quantitative adsorption analysis. However, the activated carbon used is a commercial material, marketed for this purpose. Furthermore, the removal efficiency (%) is not explored in the text, leaving many doubts as to its real application. I believe that the manuscript may be suggested for publication if some corrections are made (listed below).

• In general, the manuscript needs to be revised for its spelling and structure.

 

Authors' response: English have been improved using the commercial software Grammarly. Spelling and structure was checked in all the manuscript. Changed were marked in yellow.

 

• Please replace the word "elimination" with a more appropriate word. Line 14.

Authors' response: The word elimination was changed by removal (Page 1 line 14)

• Please rearrange the references. line 54.

Authors' response: References have been properly mentioned.

• Do the authors believe that the adsorbent should be able to retain all the compounds of a real effluent? (line 57-59) Please review this statement, if indeed it is the opinion of the authors, explore this statement further. Since 100% removal efficiency of all compounds present is quite ambitious.

No, author considered that in real effluent there are more than one component. To avoid confusions, the phrase “in real effluent” was changed for the phrase “In some cases”.

• Please correct reference 19. Line 84. - Do not include the year in citations [x], review the entire manuscript.

Authors' response: References have been corrected.

• Please add the full name of the abbreviations described in Table S1.

 

Authors' response: Abbreviation have been added to table S1.

9) Granular activated carbon sounds extremely generic. Please replace the current AC nomenclature, stating that it is commercial carbon and, preferably, the raw material used in its synthesis.

Authors' response: The nomenclature AC has been changed by GAC F400. Information about the raw material and activation processes was added to the text in line 119-120.

10) Please correct the word "adsorbent" (line 113). Aliquots were taken from the mixtures.

Authors' response. The word adsorbent was changed for adsorber. It is correct, aliquots were taken from the mixtures.

11) Figure 1 is misplaced in the manuscript.

Authors' response: The mistake has been corrected. Figure 1 correspond to the speciation diagram of MNZ and SMX.

12) Please explain in the manuscript how the authors guarantee that the temperature of 40ºC did not interfere with the drug molecule.

Authors' response: Previous studies in our research group have demonstrated that the effect of temperature in MNZ and SMX adsorption is not similar. In the case of SMX molecule, its adsorption increases when the temperature increases, meaning that SMX has an endothermic adsorption.

 

The following paragraph has been added to the text.

 

Line: 335-339:  Finally, during the adsorption of MNZ in the presence of SMX, the temperature was not a significant parameter. Carrales-Alvarado et al. [22] showed that during single adsorption of MNZ on activated carbon, the adsorption capacity at 10, 20 and 35 °C was not affected by temperature.

13) There are two "Figure 2" in the text.

Correction has been made.

14) Where is equation 4 in the supplementary material? (line 18).

Equation has been added to the supplementary material. The paragraph in the main manuscript have been rearranged as follow: “The average deviation percentage (%D) was calculated to determine the best fit between the experimental data and the model (see supplementary material)”

15) Table S2 is misplaced in the manuscript. It presents the values of dependent variables on the experimental design in the methodology.

Table S2 present the experimental design used for adsorption studies as well as the results obtained for adsorption capacities of MNZ, SMX and total. For that reason, it is mentioned in lines 145 and 291.

Round 2

Reviewer 2 Report

All comments have been responded to point-by-point by the author, and I suggest that the manuscript be accepted.